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**DBC 1101: MEDICAL BIOCHEMISTRY I** Contact hours :90 Pre requisites: None **Course purpose** This course unit is designed to provide the learner with knowledge of the concepts and principles of medical biochemistry essential for effective diagnosis and management of human diseases and disorder...
**DBC 1101: MEDICAL BIOCHEMISTRY I** Contact hours :90 Pre requisites: None **Course purpose** This course unit is designed to provide the learner with knowledge of the concepts and principles of medical biochemistry essential for effective diagnosis and management of human diseases and disorders. **Expected Learning Outcomes** By the end of the course the learner should be able to: 1\. Describe biochemical components of Human body 2\. Explain the major metabolic pathways 3\. Describe Biochemistry of Specialized Body Tissues 4\. Apply biochemical tests in management of diseases **Course Description** **Introduction and components of Human body:** Introduction, basic structures and function of membranes, extracellular matrix, common elements, the cell, DNA and RNA synthesis, Extracellular and intracellular communication. Structure, properties and functions of proteins, carbohydrates, fats, water and minerals. **Nutrition and Normal Metabolism**: Enzymes; - structure, mechanism of activity and regulation (negative and positive feedback). Metabolism of carbohydrates and glycogen, lipids/fats, Protein, urea, amino acids and derivatives, purines and pyrimidines; The Kreb\'s cycle Errors of Metabolism**:** Errors of metabolism of carbohydrates and glycogen, lipids/fats, protein, urea, uric acids and derivatives, purines and pyrimidines Hormones**:** Pituitary and hypothalamic hormones, thyroid hormones that regulate calcium metabolism, adrenal cortex and medulla hormones, gonadal hormones and pancreatic **Biochemistry of Specialized Tissues:** The brain, liver, erythrocytes, muscle, adipose tissue, body fluids- volume composition,regulation, estimation and evaluation, biochemical tests; **Functional tests:** Liver, Kidney, thyroid, adrenal, pancreas, serum proteins and enzymes **Teaching Methodology** Interactive Lectures, tutorials and Laboratory practical demonstrations, small group discussions **Instructional Materials/Equipment** LCD projector, White board, Computer, Library holdings. **Course Assessment** Continuous assessment tests accounting for 40% (assignments-10%, practical-10%, written-20%) an end of trimester written examination of 3 hours accounting for 60% of the total mark. **Course text books** 1\. Murray, R. K. (2016). Harper's Biochemistry. (30th Ed.) New York: McGraw-Hill. **ISBN** 978-0-07-182534-4 2\. Reginald, H.G. & Charles, M.G. (2012). Biochemistry. (4th Ed). Massachusetts: Brooks Cole Publishers. **ISBN**-10: 1133106293 3\. Shinde R. (2005). Text Books of Clinical Biochemistry, New Delhi: Jaypee Publishers, **ISBN** 978-93-5025-484-**4** **Course Journals** 1\. Biochemical Journal ISSN: 0264-6021 2\. Journal of Biochemistry ISSN: 1470-8728 3\. Biochemical journal ISSN: 1470-8728 **Reference text books** 1\. Wilson K. & Walker J. (2010)Principles and techniques of Biochemistry and Molecular Biology. ISBN-10: 9780521731676 2\. Critcchton, R.R. (2008). Biological Inorganic Chemistry: An Introduction. Philadelphia: Elsevier ISBN: 9780444537829 3\. Talwar, G.P. (2003). Text Book for Clinical Biochemistry and Human Biology. (3rd Ed). Prentice Hall Publishers. ISBN 10: 8120319656 46 **Reference Journals** 1\. The journal of biochemistry. ISSN: 0021-924X 2\. Turkish journal of biochemistry. ISSN: 1303-6130 3\. American journal of biochemistry, ISSN: 2163-3010 **[INTRODUCTION AND COMPONENTS OF HUMAN BODY]** - The human body is an intricate or complex biological structure that serves as the physical vessel for human beings. - It is a marvel of nature, consisting of various systems and organs that work together to support life and maintain a dynamic equilibrium known as **homeostasis.** - The human body is composed of billions of cells that are organized into tissues, which then form organs, and these organs work in unison to ensure the proper functioning of the entire body. **[Components of the Human Body]** - **Cells:** The basic building blocks of the human body. Different types of cells serve various functions and are the fundamental units of life. - **Tissues:** Groups of similar cells that come together to perform specific functions. There are four primary types of tissues: **epithelial, connective, muscle, and nervous tissues.** - **Organs:** Combinations of different tissues working together to perform specialized functions. Examples include the **heart, lungs, liver, kidneys, brain, and skin**. - **Organ Systems:** A collection of organs with related functions that work in concert to maintain the body\'s overall **homeostasis (***a self-regulating process by which a living organism can maintain internal stability while adjusting to changing external conditions***)**. The human body has several organ systems, including: - **Circulatory System:** Responsible for transporting blood, oxygen, nutrients, and waste products throughout the body. It includes the heart, blood vessels, and blood. - **Respiratory System:** Facilitates the exchange of oxygen and carbon dioxide between the body and the environment. It includes the lungs, trachea, and diaphragm. - **Digestive System:** Responsible for breaking down food and absorbing nutrients. It includes the mouth, oesophagus, stomach, intestines, liver, and pancreas. - **Nervous System:** Coordinates body activities and transmits signals between different parts of the body. It includes the brain, spinal cord, and nerves. - **Muscular System:** Enables movement and maintains posture. It includes skeletal muscles. - **Skeletal System:** Provides support, protection, and structure to the body. It includes bones, cartilage, and ligaments. - **Endocrine System:** Regulates body functions through the secretion of hormones. It includes glands like the pituitary, thyroid, adrenal, and pancreas. - **Immune System:** Defends the body against infections and diseases. It includes white blood cells, lymph nodes, and antibodies. - **Integumentary System:** Serves as a protective barrier for the body. It includes the skin, hair, and nails. - **Urinary System:** Filters and eliminates waste products from the blood. It includes the kidneys, ureters, bladder, and urethra. - **Reproductive System**: Responsible for the production of offspring. It differs between males and females and includes organs like the testes, ovaries, uterus, and external genitalia**.** **[The cell]** - Cells are the fundamental units of life and are the building blocks of all living organisms, including humans. They are incredibly diverse in structure and function, but they share some basic characteristics that define them as cells. Here are some key points about cells: - **Structure:** Cells are typically microscopic in size, ranging from a few **micrometers** to a fraction of a **millimeter**. - They are enclosed by a **cell membrane,** also known as the **plasma membrane**, which separates the ***cell\'s interior*** from the ***external environment*.** Within the cell membrane, cells contain various structures and organelles that carry out specific functions. **[Types of Cells: ]** **There are two main types of cells:** ***a. Prokaryotic Cells:*** These are simpler and smaller cells found in bacteria and archaea. Prokaryotic cells lack a true nucleus and other membrane-bound organelles. Their genetic material is organized in a single circular DNA molecule, floating in the cytoplasm. ***b. Eukaryotic Cells:*** These are more complex cells found in plants, animals, fungi, and protists. Eukaryotic cells have a true nucleus, which houses their genetic material (DNA) within a membrane-bound nucleus. They also contain various membrane-bound organelles, such as ***mitochondria, endoplasmic reticulum,** **Golgi apparatus**, and **lysosomes.*** **[Functions of the Cell]** Cells perform a wide array of functions necessary for life. These functions include energy production, protein synthesis, transport of molecules, waste elimination, growth, and reproduction. - **Metabolism:** Cells carry out metabolic processes to extract energy from nutrients and maintain their internal environment. This includes breaking down sugars (glycolysis), generating energy-rich molecules (ATP) in the mitochondria, and synthesizing proteins, lipids, and other biomolecules. - **Reproduction:** Cells can reproduce to create new cells. In unicellular organisms, cell division leads to the formation of new individuals. In multicellular organisms, cell division is essential for growth, development, and tissue repair. - **Specialization:** In multicellular organisms, cells can differentiate and specialize to perform specific functions. For example, muscle cells are specialized for contraction, nerve cells for transmitting electrical signals, and red blood cells for carrying oxygen. - **Communication:** Cells can communicate with each other through chemical signals, allowing them to coordinate their activities and respond to changes in the environment or the body\'s needs. - **Provides Support and Structure:** All the organisms are made up of cells. They form the structural basis of all the organisms. The cell wall and the cell membrane are the main components that function to provide support and structure to the organism. For eg., the skin is made up of a large number of cells. Xylem present in the vascular plants is made of cells that provide structural support to the plants. - **Facilitate Growth Mitosis:** In the process of mitosis, the parent cell divides into the daughter cells. Thus, the cells multiply and facilitate the growth in an organism. - **Allows Transport of Substances:** Various nutrients are imported by the cells to carry out various chemical processes going on inside the cells. The waste produced by the chemical processes is eliminated from the cells by active and passive transport. Small molecules such as oxygen, carbon dioxide, and ethanol diffuse across the cell membrane along the concentration gradient. This is known as passive transport. The larger molecules diffuse across the cell membrane through active transport where the cells require a lot of energy to transport the substances. - There are several ways to consider the composition of the human body, including **[the elements](https://www.thoughtco.com/what-is-a-chemical-element-604297), [type of molecule](https://www.thoughtco.com/chemical-composition-of-the-human-body-603995),** or **[type of cells](https://www.thoughtco.com/types-of-cells-in-the-body-373388). ** - Most of the human body is made up of **water,** with **bone cells** being comprised of ***31% water*** and the ***lungs 83%.*** - Therefore, it isn\'t surprising that most of a human body\'s mass is oxygen. Carbon, the basic unit for organic molecules, comes in second. **96.2%** of the mass of the human body is made up of just four elements: oxygen, carbon, hydrogen, and nitrogen. - Nearly 99% of the mass of your human body consists of just 6 chemical elements: ***oxygen, carbon, hydrogen, nitrogen, calcium, and phosphorus***. - Another 5 elements make up most of the last percentage point: ***potassium, sulfur, sodium, chlorine,*** and ***magnesium.*** - **Oxygen** (O) - 65% - Oxygen together with hydrogen form water, which is the primary solvent found in the body and is used to regulate temperature and osmotic pressure. Oxygen is found in many key organic compounds. - **Carbon** (C) - 18.5% - Carbon has four bonding sites for other atoms, which makes it the key atom for organic chemistry. Carbon chains are used to build carbohydrates, fats, nucleic acids, and proteins. Breaking bonds with carbon is an energy source. - **Hydrogen**(H) - 9.5% - Hydrogen is found in water and in all organic molecules. - **Nitrogen**(N) - 3.2% - Nitrogen is found in proteins and in the nucleic acids that make up the genetic code. - **Calcium** (Ca) - 1.5% - Calcium is the [**most abundant**](https://www.thoughtco.com/most-abundant-element-in-the-universe-602186) [ ] mineral in the body. It\'s used as a structural material in bones, but it is essential for protein regulation and muscle contraction. - **Phosphorus**(P) - 1.0% - Phosphorus is found in [**the molecule ATP**](https://www.thoughtco.com/atp-important-molecule-in-metabolism-4050962), which is the primary energy carrier in cells. It\'s also found in bone. - **Potassium**(K) - 0.4% - Potassium is an important electrolyte. It\'s used to transmit nerve impulses and heartbeat regulation. - **Sodium** (Na) - 0.2% - Sodium is an important electrolyte. Like potassium, it is used for nerve signalling. Sodium is one of the electrolytes that helps regulate the amount of water in the body. - **Chlorine** (Cl) - 0.2% - Chlorine is an important negatively-charged ion (anion) used to maintain fluid balance. - **Magnesium** (Mg) - 0.1% - Magnesium is involved in over 300 metabolic reactions. It\'s used to build the structure of muscles and bones and is an important cofactor in enzymatic reactions. - **Sulfur** (S) - 0.04% - Two amino acids include sulfur. The bonds sulfur forms help give proteins the shape they need to perform their functions. - Many other elements may be found in extremely small quantities (less than 0.01%). For example, the human body often contains trace amounts of thorium, uranium, samarium, tungsten, beryllium, and radium. Trace elements considered essential in humans include zinc, selenium, nickel, chromium, manganese, cobalt, and lead. - Not all of the elements found within the body are essential for life. Some are considered contaminants that appear to do no harm but serve no known function. Examples include [cesium](https://www.thoughtco.com/cesium-element-facts-606517) and titanium. Others are actively toxic, including [mercury](https://www.thoughtco.com/mercury-facts-606560), cadmium, and [radioactive elements](https://www.thoughtco.com/the-most-radioactive-element-608920). - Arsenic is considered to be toxic to humans, but serves a function in other mammals (goats, rats, hamsters) in trace amounts. Aluminium is interesting because it is the third most common element in the Earth\'s crust, but its role in the human body is unknown. While fluorine is used by plants to produce protective toxins and has \"apparent beneficial intake\" in humans - Cells are the basic, fundamental unit of life. So, if we were to break apart an organism to the cellular level, the smallest independent component that we would find would be the cell. - Explore the cell notes to know what is a cell, cell definition, cell structure, types and functions of cells. These notes have an in-depth description of all the concepts related to cells. **[Characteristics of Cells]** - The following are the various essential characteristics of cells: - *Cells provide structure and support to the body of an organism.* - *The cell interior is organised into different individual organelles surrounded by a separate membrane.* - *The nucleus (major organelle) holds genetic information necessary for reproduction and cell growth.* - *Every cell has one nucleus and membrane-bound organelles in the cytoplasm.* - *Mitochondria, a double membrane-bound organelle is mainly responsible for the energy transactions vital for the survival of the cell.* - *Lysosome's digest unwanted materials in the cell.* - *Endoplasmic reticulum plays a significant role in the internal organisation of the cell by synthesising selective molecules and processing, directing and sorting them to their appropriate locations*. ***[Cell Organelles (Personal Reading Assignment)]*** **[Cell Theory]** - In 1838, a German botanist Mathias Jacob Schleiden (1804---1881) put forth the idea that cells were the units of structure in the plants. - In 1839, his co-worker, a German zoologist, Theodor Schwann (1810---1882) applied Schleiden's thesis to the animals. - Both of them, thus, postulated that the cell is the basic unit of structure and function in all life. - This simple, basic and formal biological generalization is known as cell theory or cell doctrine. - In fact, both Schleiden and Schwann are incorrectly credited for the formulation of the cell theory; they merely made the generalizations which were based on the works of their predecessors such as Oken (1805), Mirbel (1807), Lamarck (1809), Dutrochet (1824), Turpin (1826), etc. - However, Schleiden was the first to describe the nucleoli and to appreciate the fact that each cell leads a double life---one independent, pertaining to its own development, and another as integral part of a multi-cellular plant. - Schwann studied both plant and animal tissues and his work with the connective tissues such as bone and cartilage led him to modify the evolving cell theory to include the idea that living things are composed of both cells and the products or secretions of the cells. - Schwann also introduced the term metabolism to describe the activities of the cells. - In the coming years, the cell theory was to be extended and refined further. K. Nageli (1817---1891) showed in 1846 that plant cells arise from the division of pre-existing cells. - In 1855, a German pathologist Rudolf Virchow (1821---1902) confirmed the Nageli's principle of the cellular basis of life's continuity. He stated in Latin that the cells arise only from the pre-existing cells. - Virchow, thus, established the significance of cell division in the reproduction of organisms. - In 1858, Virchow published his classical textbook Cellular Pathology and in it he correctly asserted that as functional units of life, the cells were the primary sites of disease and cancer. - Later, in 1865, Louis Pasteur (1822---1895) in France gave experimental evidence to support Virchow's extension of the cell theory. The modern version of cell theory states that *1. All living organisms (animals, plants and microbes) are made up of one or more cells and* *cell products.* *2. All metabolic reactions in unicellular and multi-cellular organisms take place in cells.* *3. Cells originate only from other cells, i.e., no cell can originate spontaneously or de novo,* *but comes into being only by division and duplication of already existing cells.* *4. The smallest clearly defined unit of life is the cell.* The cell theory had its wide biological applications. - With the progress of biochemistry, it was shown that there were fundamental similarities in the chemical composition and metabolic activities of all cells. - Kolliker applied the cell theory to embryology---after it was demonstrated that the organisms developed from the fusion of two cells---the spermatozoon and the ovum. - However, in the recent years, large number of sub-cellular structures such as ribosomes, lysosomes, mitochondria, chloroplasts, etc., has been discovered and studied in detail. - Consequently, it may appear that cell is no longer a basic unit of life, because life may exist without cells also. Even then, the cell theory remains a useful concept. ***Exception** **to cell theory*** Cell theory does not have universal application, i.e., there are certain living organisms which do not have true cells. All kinds of true cells share the following three basic characteristics: 1\. A set of genes which constitute the blueprints for regulating cellular activities and making new cells. 2\. A limiting plasma membrane that permits controlled exchange of matter and energy with the external world. 3\. A metabolic machinery for sustaining life activities such as growth, reproduction and repair of parts. **[Basic structures and function of;]** **[A. MEMBRANES]** The **cell membrane**, also known as the **plasma membran**e, is a fundamental component of cells that separates the interior of the cell from its external environment. It plays a crucial role in maintaining cellular integrity and regulating the movement of substances in and out of the cell. The cell membrane is primarily composed of a lipid bilayer with embedded proteins. Here\'s a basic overview of its structure and functions: **Plasma Membrane** 1. **A** plasma membrane encloses every type of cell, both prokaryotic and eukaryotic cells. 2. It physically separates the cytoplasm from the surrounding cellular environment. 3. Plasma membrane is an ultrathin, elastic, living, dynamic and selective transport-barrier. 4. It is a fluid-mosaic assembly of molecules of lipids (phospholipids and cholesterol), proteins and carbohydrates. 5. Plasma membrane controls the entry of nutrients and exit of waste products, and generates differences in ion concentration between the interior and exterior of the cell. 6. It also acts as a sensor of external signals (for example, hormonal, immunological, etc.) and allows the cell to react or change in response to environmental signals. 7. The cells of bacteria and plants have the plasma membrane between the cell wall and the cytoplasm. For cells without cell walls (*e.g*., mycoplasma and animal cells), plasma membrane forms the cell surface. 8. All biological membranes including the plasma membrane and internal membranes of eukaryotic cells (*i.e.*, membranes bounding endoplasmic reticulum or ER, nucleus, mitochondria, chloroplast, Golgi apparatus, lysosomes, peroxisomes, etc.) are similar in structure (*i.e*., fluid-mosaic) and selective permeability but differing in other functions. 9. The plasma membrane is also called **cytoplasmic membrane**, **cell membrane,** or **plasmalemma**. **[CHEMICAL COMPOSITION]** Chemically, plasma membrane and other membranes of different organelles are found to contain proteins, lipids and carbohydrates, but in different ratios. For example, in the plasma membrane of human red blood cells proteins represent 52 per cent, lipids 40 per cent and carbohydrates **[1. Lipids (Forms the bilayer)]** - The core structure of the cell membrane is a lipid bilayer composed of phospholipids. Each phospholipid molecule has a hydrophilic (water-attracting) head and two hydrophobic (water-repelling) tails. - These molecules arrange themselves in a double layer, with their hydrophobic tails pointing inward and their hydrophilic heads facing outward toward the surrounding aqueous environment. - Four major classes of lipids are commonly present in the plasma membrane and other membranes: a. **Phospholipids** (most abundant), b. **Sphingolipids**, c. **Glycolipids** and d. **Sterols** (*e.g.*, **cholesterol**). - All of them are amphipathic molecules, possessing both hydrophilic and hydrophobic domains. - The relative proportions of these lipids vary in different membranes. - Phospholipids may be **acidic phospholipids** (20 per cent) such as **sphingomyelin** or **neutral phospholipids** (80 per cent) such as **phosphatidyl choline**, **phosphatidylserine**, etc. - Many membranes contain cholesterol. - Cholesterol is especially abundant in the plasma membrane of mammalian cells and absent from prokaryotic cells. - **Cardiolipin** (diphosphatidyl glycerol) is restricted to the inner mitochondrial membrane. **[2. Proteins]** - Embedded within the lipid bilayer are various types of proteins that serve essential functions for the cell. These proteins can be classified into two main categories: **integral proteins** and p**eripheral proteins.** - **Integral/Intrinsic Proteins**: These proteins are firmly embedded within the lipid bilayer, spanning from one side to the other (associate firmly with the membrane). - They can have hydrophobic regions that interact with the lipid tails and hydrophilic regions that interact with the aqueous environment. Integral proteins can act as channels, carriers, receptors, and enzymes. - **Peripheral Proteins:** These proteins are associated with the membrane\'s surface, either on the cytoplasmic side(endoproteins) or the extracellular side(ectoproteins). They do not penetrate the lipid bilayer and are often involved in signalling, structural support, and cell adhesion. - They may either have a weaker association or bound to lipids of membrane by electrostatic interaction. The amount and types of proteins in the membranes are highly variable: - In the myelin membranes which serve mainly to insulate nerve cell axons, less than 25 per cent of the membrane mass is protein, whereas, - In the membranes involved in energy transduction (such as internal membranes of mitochondria and chloroplasts), approximately 75 per cent is protein. - Plasma membrane contains about 50 per cent protein. a. **Transport proteins** - These transmembrane proteins can form a pore or channel in the membrane that is selective for certain molecules. It is also possible that they transport molecules by changing shape. Some require energy (ATP) for this transport. **Example:** **glucose transporter;** *are protein molecules that facilitate the transport of glucose across cell membranes. These transporters play a crucial role in maintaining glucose homeostasis in the body. There are several types of glucose transporters, including GLUT1, GLUT2, GLUT3, and GLUT4, which are found in different tissues and have distinct characteristics.* b. **Enzymes** - These proteins have enzymatic activity. The active site is inside the cell. These proteins can occur as groups to facilitate a series of enzymatic processes. **Example:** **tyrosine kinases;** *is an enzyme that plays a crucial role in cell signalling and regulation. It phosphorylates specific tyrosine residues on proteins, thereby initiating various downstream signalling pathways. This process is important for cellular processes such as growth, differentiation, and proliferation.* c. **Signal transduction proteins** - These proteins receive a signal from outside the cell and convert this to a signal inside the cell. A signal molecule can for example change the shape of the protein allowing a protein from inside the cell to bind to the receptor. **Example:** **G-proteins;** *are a group of proteins that play a crucial role in signal transduction pathways. They act as molecular switches, relaying signals from cell surface receptors to intracellular effectors. Due to their diverse functions and involvement in various biological processes, G-proteins are highly important in cellular communication.* d. **Recognition proteins** - Some of these proteins contain a certain \'tag\' (usually a sugar) that can be recognized by membrane proteins of other cells. This way cells can communicate with each other (transient). The tag can also be used to differentiate between different types of cells. Example: glycoproteins that determine blood type (ABO blood types) e. **Joining proteins** - These proteins also bind to other membrane proteins as the previous proteins. In this case, however, the connection is tighter and lasts longer. \' - Example: **tight junction;** *are composed of protein complexes, such as claudins and occludins, which form a barrier that restricts the passage of substances. Dysfunction of tight junctions can lead to various diseases, highlighting their importance in cellular physiology and homeostasis* f. **Attachment** - You asked for 5, but Campbell describes 6. This can be considered similar to \#5; only in this case the protein doesn\'t attach to other cells but to the cytoskeleton inside the cell or the matrix outside the cell. **[3. Carbohydrates]** - Carbohydrates play a crucial role in the structure and function of the plasma membrane. They are often found on the outer surface of the cell membrane, associated with proteins and lipids. - These carbohydrate molecules attached to proteins and lipids are collectively referred to as glycoproteins and glycolipids, respectively. - This complex arrangement of carbohydrates, proteins, and lipids on the cell membrane\'s surface is often referred to as the **glycocalyx**. Here\'s how carbohydrates contribute to the plasma membrane: a. **Cell-Cell Recognition and Adhesion:** Carbohydrates in the form of glycoproteins and glycolipids participate in cell-cell recognition and adhesion. The unique arrangement of carbohydrates on the cell surface allows cells to identify and interact with one another. This is particularly important in processes like immune response, where cells need to distinguish between self and non-self cells. b. **Cell Signalling:** Carbohydrates on the cell membrane can serve as receptors for signalling molecules such as hormones. When a signalling molecule binds to a carbohydrate receptor, it can initiate a signalling cascade inside the cell, leading to specific cellular responses. c. **Protection and Lubrication:** The glycocalyx formed by carbohydrate-protein and carbohydrate-lipid interactions can act as a protective layer for the cell. It helps protect the cell from mechanical damage and provides lubrication for cell movements, such as the movement of white blood cells through blood vessels. d. **Cell Adhesion:** Carbohydrates on the cell surface play a role in cell adhesion, helping cells stick together to form tissues and organs. They contribute to the formation of cell-cell junctions and help stabilize tissue structures. e. **Pathogen Recognition**: Carbohydrates on the cell membrane can also play a role in recognizing pathogens such as bacteria and viruses. This recognition can trigger immune responses to defend the body against infections. f. **Blood Type Determination:** Carbohydrates on the surface of red blood cells determine blood types in the ABO blood group system. These carbohydrates are specific to different blood types and play a role in compatibility for blood transfusions. **[Summary of the function of membranes]** 1. **Selective Permeability:** One of the most fundamental functions of the cell membrane is to regulate the movement of substances in and out of the cell. It acts as a selectively permeable barrier, allowing certain molecules and ions to pass through while preventing others from crossing freely. This helps maintain the internal environment of the cell and ensures that necessary substances enter the cell while waste products and potentially harmful molecules are kept out. 2. **Transport:** The cell membrane contains proteins that facilitate the transport of molecules across it. These proteins can function as channels, carriers, and pumps. Channels allow specific ions or molecules to move down their concentration gradients, carriers facilitate the movement of larger molecules through facilitated diffusion, and pumps actively transport molecules against their concentration gradients using energy. 3. **Cell signalling:** Receptor proteins on the cell membrane\'s surface interact with signalling molecules, such as hormones, neurotransmitters, and growth factors. When a signalling molecule binds to its corresponding receptor, it triggers a cellular response, often leading to changes in gene expression, enzyme activity, or other intracellular processes. 4. **Cell Adhesion:** Cell adhesion proteins on the cell membrane enable cells to stick together, which is essential for forming tissues and organs. They also play a role in maintaining the structural integrity of tissues and facilitating communication between neighbouring cells. 5. **Cell Recognition and Immune Response:** Carbohydrates on the cell membrane\'s surface play a role in cell recognition. They help the immune system distinguish between self and non-self cells and are involved in immune responses against pathogens. 6. **Protection and Physical Barrier:** The cell membrane forms a protective barrier that shields the cell\'s internal components from the external environment. It prevents the entry of harmful substances and pathogens and helps maintain the cell\'s structural integrity. 7. **Cellular Communication:** Gap junctions and tight junctions formed by proteins in the cell membrane enable direct communication between adjacent cells. Gap junctions allow the passage of ions and small molecules, facilitating coordination and synchronization of cellular activities in tissues. 8. **Osmoregulation:** The cell membrane helps regulate the balance of water and solutes inside the cell. It controls the movement of water through processes like osmosis, preventing excessive swelling or shrinking of cells. 9. **Endocytosis and Exocytosis:** The cell membrane is involved in processes like endocytosis (cellular uptake of substances by forming vesicles) and exocytosis (secretion of substances from the cell by vesicle fusion with the membrane). These processes are crucial for nutrient uptake, waste removal, and cell communication. 10. **Energy Production:** The cell membrane houses proteins involved in electron transport chains and ATP synthesis in certain types of cells, such as mitochondria and chloroplasts, contributing to energy production. [**B**. **EXTRACELLULAR MATRIX**] - The extracellular matrix (ECM) is a complex network of proteins and carbohydrates that surrounds and supports cells within **tissues** and organs in multicellular organisms. - It *provides* *structural integrity, mechanical support,* *guides cell division*, *growth & development* and *biochemical signalling* to cells. In other words, the extracellular matrix largely determines how a tissue looks and functions. - The ECM is found in various types of tissues, including **connective tissues**, such as **bone, cartilage**, and **tendons,** as well as **epithelial, muscle,** and **nervous tissues.** - The extracellular matrix is made up of **proteoglycans, water, minerals, and fibrous proteins**. A **proteoglycan** is composed of a protein core surrounded by long chains of starch-like molecules called glycosaminoglycans. **[Production and Components]** - Two main classes of molecules can be found in the extracellular matrix: **fibrous proteins** and **proteoglycans.** a. **[Fibrous Proteins]** - Several types of **fibrous proteins**, including ***collagen, elastin, fibronectin***, and ***laminin,*** are found in varying amounts within the *extracellular matrix of different tissues.* - **Collagen** is a strong, stretch-resistant fiber that provides tensile strength to your tissues. It\'s the most abundant protein in the human body. Collagen is the principle constituent of tendons and ligaments and provides support for your skin. When you sustain an injury to your skin, collagen is the stuff that heals the wound and forms the scar. There are at least a dozen different types of collagens in your body, all adapted to the specific needs of the tissues where they\'re found. - **Elastin** is a stretchy and resilient protein. Much like a rubber band, elastin permits tissues to return to their original shape after they\'ve been stretched. Ultraviolet light damages elastin fibers and interferes with their reconstruction, which accounts for the sagging and wrinkling seen in skin that has been chronically exposed to sunlight. - **Fibronectin** is secreted from fibroblasts in a water-soluble form but is quickly assembled into an insoluble meshwork, which serves several functions. Other cells use the fibronectin matrix to migrate through a tissue, which is particularly important during embryonic development; fibronectin helps position cells within the extracellular matrix; and fibronectin is necessary for cellular division and specialization in many tissues. - **Laminin** forms sheet-like networks that serve as the \'glue\' between dissimilar tissues. It is the principle protein in **basement membranes**, which are present wherever connective tissue contacts muscle, nervous, or epithelial tissue. b. **[Proteoglycans]** - In contrast to fibrous proteins, which provide resistance to stretching forces, **proteoglycans** provide resistance to compressive, or \'squashing,\' forces. This property stems primarily from the **glycosaminoglycan** portion of **proteoglycans**. - **Proteoglycans** are [proteins](https://en.wikipedia.org/wiki/Protein) that are heavily [glycosylated](https://en.wikipedia.org/wiki/Glycosylation). The basic proteoglycan unit consists of a \"core [protein](https://en.wikipedia.org/wiki/Protein)\" with one or more [covalently](https://en.wikipedia.org/wiki/Covalent_bond) attached [glycosaminoglycan](https://en.wikipedia.org/wiki/Glycosaminoglycan) (GAG) chain(s). - The point of attachment is a [serine](https://en.wikipedia.org/wiki/Serine) (Ser) residue to which the glycosaminoglycan is joined through a tetrasaccharide bridge (e.g. [chondroitin sulfate](https://en.wikipedia.org/wiki/Chondroitin_sulfate)-[GlcA](https://en.wikipedia.org/wiki/GlcA)-[Gal](https://en.wikipedia.org/wiki/Galactose)-Gal-[Xyl](https://en.wikipedia.org/wiki/Xylose)-PROTEIN). - The Ser residue is generally in the sequence -Ser-[Gly](https://en.wikipedia.org/wiki/Gly)-X-Gly- (where X can be any amino acid residue but [proline](https://en.wikipedia.org/wiki/Proline)), although not every protein with this sequence has an attached glycosaminoglycan. - The chains are long, linear carbohydrate polymers that are negatively charged under physiological conditions due to the occurrence of [sulfate](https://en.wikipedia.org/wiki/Sulfate) and [uronic acid](https://en.wikipedia.org/wiki/Uronic_acid) groups. Proteoglycans occur in [connective tissue](https://en.wikipedia.org/wiki/Connective_tissue). **[Types]** - Proteoglycans are categorized by their relative size (large and small) and the nature of their glycosaminoglycan chains. - Types include: i. *[Heparan sulfate proteoglycan](https://en.wikipedia.org/wiki/Heparan_sulfate_proteoglycan) (HSPGs)* ii. *[Chondroitin sulfate proteoglycan](https://en.wikipedia.org/wiki/Chondroitin_sulfate_proteoglycan)(CSPGs)* iii. [*Keratan sulfate proteoglycan*](https://en.wikipedia.org/w/index.php?title=Keratan_sulfate_proteoglycan&action=edit&redlink=1) **[Function]** - Proteoglycans are a major component of the animal [extracellular matrix](https://en.wikipedia.org/wiki/Extracellular_matrix), the \"filler\" substance existing between [cells](https://en.wikipedia.org/wiki/Cell_(biology)) in an organism. Here they form large complexes, both to other proteoglycans, to [hyaluronan](https://en.wikipedia.org/wiki/Hyaluronan), and to fibrous matrix proteins, such as [collagen](https://en.wikipedia.org/wiki/Collagen). - The combination of proteoglycans and collagen form [cartilage](https://en.wikipedia.org/wiki/Cartilage), a sturdy tissue that is usually heavily hydrated (mostly due to the negatively charged sulphates in the glycosaminoglycan chains of the proteoglycans). - They are also involved in binding [cations](https://en.wikipedia.org/wiki/Cations) (such as [sodium](https://en.wikipedia.org/wiki/Sodium), [potassium](https://en.wikipedia.org/wiki/Potassium) and [calcium](https://en.wikipedia.org/wiki/Calcium)) and [water](https://en.wikipedia.org/wiki/Water), and also regulating the movement of molecules through the matrix. Individual functions of proteoglycans can be attributed to either the protein core or the attached GAG chain. They can also serve as lubricants, by creating a hydrating gel that helps withstand high pressure. **[Clinical significance]** - An inability to break down the proteoglycans is characteristic of a group of [genetic disorders](https://en.wikipedia.org/wiki/Genetic_disorder), called [**mucopolysaccharidoses**](https://en.wikipedia.org/wiki/Mucopolysaccharidoses). - The inactivity of specific [lysosomal](https://en.wikipedia.org/wiki/Lysosome) enzymes that normally degrade glycosaminoglycans leads to the accumulation of proteoglycans within cells. This leads to a variety of disease symptoms, depending upon the type of proteoglycan that is not degraded. - Mutations in the gene encoding the galactosyltransferase [B4GALT7](https://en.wikipedia.org/wiki/B4GALT7) result in a reduced substitution of the [proteoglycans](https://en.wikipedia.org/wiki/Proteoglycans) [decorin](https://en.wikipedia.org/wiki/Decorin) and [biglycan](https://en.wikipedia.org/wiki/Biglycan) with [glycosaminoglycan](https://en.wikipedia.org/wiki/Glycosaminoglycan) chains, and cause a spondylodysplastic form of [Ehlers-Danlos syndrome](https://en.wikipedia.org/wiki/Ehlers-Danlos_syndrome). **[Distinction between proteoglycans and [glycoproteins](https://en.wikipedia.org/wiki/Glycoprotein)]** - **A [glycoprotein](https://en.wikipedia.org/wiki/Glycoprotein)** is a compound containing carbohydrate (or glycan) covalently linked to protein. The carbohydrate may be in the form of a monosaccharide, disaccharide(s). oligosaccharide(s), polysaccharide(s), or their derivatives (e.g., sulfo- or phospho-substituted). One, a few, or many carbohydrate units may be present. - **Proteoglycans are a subclass of glycoproteins** in which the carbohydrate units are polysaccharides that contain amino sugars. Such polysaccharides are also known as glycosaminoglycans. **[EXTRACELLULAR AND INTRACELLULAR COMMUNICATION.]** There are two kinds of communication in the world of living cells. Communication between cells is called **intercellular signaling**, and communication within a cell is called **intracellular signaling**. An easy way to remember the distinction is by understanding that the prefix inter- means "between" (an interstate highway crosses between states) and intra- means "inside" **[Forms of Signaling]** There are four categories of chemical signaling found in multicellular organisms: **autocrine** **signaling,** **paracrine** **signaling**, **endocrine** **signaling,** and **direct** **signaling** across **gap junctions**. The main difference between the different categories of signaling is the distance that the signal travels to reach the target cell. 9.2: Signaling Molecules and Cellular Receptors - Forms of Signaling - Biology LibreTexts 1. **Autocrine Signaling** When a cell responds to its own signaling molecule, it is called **autocrine** signaling (auto = "self"). Autocrine signaling often occurs with other types of signaling. For example, when a paracrine signal is released, the signaling cell may respond to the signal along with its neighbours (**Figure 9.2**). Autocrine signaling often occurs during early development of an organism to ensure that cells develop into the correct tissues. Autocrine signaling also regulates pain sensation and inflammatory responses. Further, if a cell is infected with a virus, the cell can signal itself to undergo programmed cell death, killing the virus in the process. 2. **Endocrine Signaling** Signals from distant cells are called **endocrine signals**, and they originate from **endocrine cells**. (In the body, many endocrine cells are located in endocrine glands, such as the thyroid gland, the hypothalamus, and the pituitary gland.) These types of signals usually produce a slower response but have a longer-lasting effect. The ligands released in endocrine signaling are called **hormones**, signaling molecules that are produced in one part of the body but affect other body regions some distance away (**Figure above**). Hormones travel the large distances between endocrine cells and their target cells via the bloodstream, which is a relatively slow way to move throughout the body. Because of their form of transport, hormones get diluted and are present in low concentrations when they act on their target cells. This is different from paracrine signaling, in which local concentrations of signaling molecules can be very high. 3. **Direct Signaling** Gap junctions in animals and plasmodesmata in plants are connections between the plasma membranes of neighbouring cells. These water-filled channels allow small signaling molecules to diffuse between the two cells. Small molecules, such as calcium ions (Ca^2+^), are able to move between cells, but large molecules like proteins and DNA cannot fit through the channels. The specificity of the channels ensures that the cells remain independent but can quickly and easily transmit signals. Direct signaling allows a group of cells to coordinate their response to a signal that only one of them may have received. In plants, plasmodesmata are ubiquitous, making the entire plant into a giant communication network. 4. **Paracrine Signaling** Signals that act locally between cells that are close together are called paracrine signals. Paracrine signals move by diffusion through the extracellular matrix (Figure 9.2). These types of signals usually elicit quick responses that last only a short amount of time. In order to keep the response localized, paracrine ligands are usually quickly degraded by enzymes or removed by neighboring cells. Removing the signals reestablishes the concentration gradient for the signal molecule, allowing them to quickly diffuse through the intracellular space if released again. ![](media/image3.png) **[Types of Receptors]** Receptors are protein molecules in the target cell or on its surface that bind to ligands. There are two types of receptors, internal receptors and cell-surface receptors. A. **[Internal receptors]** - Internal receptors, also known as intracellular receptors or nuclear receptors, are a class of proteins found within cells that play a crucial role in mediating cellular responses to various signaling molecules. - These receptors are typically located within the cytoplasm or nucleus of the cell and are involved in regulating gene expression. They are a key component of the cell\'s ability to respond to hormones, steroids, and other small signaling molecules. - Here are some key characteristics and functions of internal receptors: - **Ligand Binding:** Internal receptors are activated when specific signaling molecules, often referred to as ligands, bind to them. These ligands can include hormones such as steroid hormones (e.g., estrogen, testosterone, cortisol), thyroid hormones, and retinoic acid, among others. - **Intracellular Localization:** Internal receptors are typically found within the cytoplasm or nucleus of the cell, depending on the specific receptor type. For example, steroid hormone receptors are usually in the cytoplasm until they bind their ligands, after which they translocate into the nucleus to affect gene transcription. - **Gene Regulation**: Once activated by ligand binding, internal receptors can directly regulate gene expression. They function as transcription factors, which means they can either enhance or suppress the transcription of specific genes. This regulation is essential for controlling various cellular processes, including growth, differentiation, metabolism, and immune response. - **DNA Binding:** Internal receptors often have a DNA-binding domain that allows them to bind to specific DNA sequences called hormone response elements (HREs) or hormone-responsive elements (HREs) in the promoter regions of target genes. This binding to DNA is essential for initiating or inhibiting gene transcription. - **Diverse Functions:** Internal receptors have diverse functions and are involved in many physiological processes. For example, the estrogen receptor is crucial for female sexual development and reproductive function, while the glucocorticoid receptor plays a role in regulating stress responses and immune function. - **Ligand Diversity:** Different internal receptors have specific ligand-binding preferences. For instance, the androgen receptor binds to androgens like testosterone, while the thyroid hormone receptor binds to thyroid hormones like thyroxine. - **Pharmaceutical Targets:** Internal receptors are targets for many pharmaceutical drugs. Modulating their activity with drugs can have therapeutic effects, such as in hormone replacement therapy, cancer treatment, and autoimmune disease management. image *Figure 9.4 Hydrophobic signaling molecules typically diffuse across the plasma membrane and interact with intracellular receptors in the cytoplasm. Many intracellular receptors are transcription factors that interact with DNA in the nucleus and regulate gene expression*. B. **[Cell-Surface Receptors]** - Cell surface receptors, also known as membrane receptors or cell membrane receptors, are proteins located on the surface of a cell\'s plasma membrane. These receptors play a crucial role in transmitting signals (signal transduction) from the extracellular environment to the inside of the cell. - They are essential for a wide range of cellular processes, including cell communication, response to environmental stimuli, and the regulation of various physiological functions. - Errors in the protein structures of certain receptor molecules have been shown to play a role in hypertension (high blood pressure), asthma, heart disease, and cancer. - Here are some key characteristics and functions of cell surface receptors: - **Extracellular Ligand Binding**: Cell surface receptors primarily function by binding to specific signaling molecules, known as ligands, that are present in the extracellular fluid. These ligands can be hormones, neurotransmitters, growth factors, cytokines, or other molecules involved in cell signaling. - **Transmembrane Proteins:** Cell surface receptors are integral membrane proteins, meaning they span the cell\'s lipid bilayer, with portions of the receptor exposed on both the extracellular and intracellular sides of the membrane. - **Signal Transduction:** Upon ligand binding, cell surface receptors transmit signals across the plasma membrane and initiate intracellular responses. This process, known as signal transduction, involves a series of molecular events that relay the extracellular signal to the cell\'s interior. - **Diversity of Receptor Types:** There are several types of cell surface receptors, each with its specific structure and mechanism of action. Common types include G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), ligand-gated ion channels, and cytokine receptors. - **G Protein-Coupled Receptors (GPCRs):** GPCRs are a large and diverse family of cell surface receptors that activate intracellular signaling pathways through the activation of G proteins. They are involved in numerous physiological processes and are the target of many pharmaceutical drugs. - **Receptor Tyrosine Kinases (RTKs):** RTKs are cell surface receptors that have intrinsic kinase activity. Ligand binding activates the kinase domain, leading to the phosphorylation of tyrosine residues on the receptor itself and downstream signaling molecules. They play a critical role in cell growth, differentiation, and proliferation. - **Ligand-Gated Ion Channels**: These receptors, often found in nerve and muscle cells, directly control the flow of ions across the plasma membrane in response to ligand binding. This can lead to changes in membrane potential and cellular excitability. - **Cytokine Receptors:** Cytokine receptors are involved in immune responses and inflammation. They activate intracellular signaling pathways in response to cytokine binding, regulating immune cell function and other processes. - **Drug Targets**: Many drugs, including various medications and therapeutic agents, target cell surface receptors to modulate cellular responses. This is a common approach in medicine for managing diseases and disorders. - **Cell Communication:** Cell surface receptors are crucial for intercellular communication, allowing cells to respond to signals from neighboring cells or distant tissues. This communication is vital for maintaining tissue homeostasis and coordinating physiological processes. ![image](media/image5.jpeg) ***Figure 9.5** Hydrophilic signaling molecules typically work by binding to the extracellular portion of a receptor protein. The signal is then transduced across the membrane*. C. **[Enzyme-linked receptors ]** - These are cell-surface receptors with intracellular domains that are associated with an enzyme. In some cases, the intracellular domain of the receptor itself is an enzyme. Other enzyme-linked receptors have a small intracellular domain that interacts directly with an enzyme. - Enzyme-linked receptors normally have large extracellular and intracellular domains, but the membrane-spanning region consists of a single alpha-helix in the peptide strand. - When a ligand binds to the extracellular domain of an enzyme-linked receptor, a signal is transferred through the membrane, activating the enzyme. Activation of the enzyme sets off a chain of events within the cell that eventually leads to a response. - Example of an enzyme-linked receptor is the **tyrosine kinase receptor.** A **kinase** is an enzyme that transfers phosphate groups from ATP to another protein. The tyrosine kinase receptor transfers phosphate groups to tyrosine molecules. First, signaling molecules bind to the extracellular domain of two nearby tyrosine kinase receptors. The two neighboring receptors then bond together, or dimerize. Phosphates are then added to tyrosine residues on the intracellular domain of the receptors (phosphorylation). The phosphorylated residues can then transmit the signal to the next messenger within the cytoplasm. - Epidermal growth factor receptors are an example of receptor tyrosine kinases that follows this mode of signaling. Defects in ErbB signaling in this family can lead to neuromuscular diseases such as multiple sclerosis and Alzheimer's disease. D. **[Ion channel-linked receptors]** - They bind to a ligand and open a channel through the membrane that allows specific ions to pass through. This type of cell-surface receptor has an extensive membrane-spanning region with hydrophobic amino acids. - Conversely, the amino acids that line the inside of the channel are hydrophilic to allow for the passage of ions. - When a ligand binds to the extracellular region of the channel, there is a conformational change in the protein's structure that allows ions such as sodium, calcium, magnesium, or hydrogen to pass through (**Figure below**). image ***Figure 9.7** Ion channel-linked receptors open and allow ions to enter a cell. An example of an ion channel-linked receptor is found on neurons. When neurotransmitters bind to these receptors, a conformational change allows sodium ions to flow across the cell membrane, causing a change in the membrane potential.* E. **[G-protein-linked receptors]** - They bind to a ligand and activate an associated G-protein. The activated G- protein then interacts with a nearby membrane protein, which may be an ion channel or an enzyme. - All G-protein-linked receptors have seven transmembrane domains, but each receptor has a specific extracellular domain and G-protein-binding site. **[Signaling Molecules]** - Produced by signaling cells, ligands are chemical signals that travel to target cells and cause a response. The types of molecules that serve as ligands are incredibly varied and range from small proteins to small ions. - Ligands are categorized as either small hydrophobic ligands, which can cross plasma membranes, or water-soluble ligands, which cannot. i. **[Small Hydrophobic Ligands]** - Small hydrophobic ligands, also called lipid-soluble ligands, can directly diffuse through the plasma membrane and interact with internal receptors. Important members of this class of ligands are the steroid hormones. - Steroids are lipids that have a hydrocarbon skeleton with four fused rings; different steroids have different functional groups attached to the carbon skeleton. Steroid hormones include the female sex hormone estradiol, which is a type of estrogen; the male sex hormone testosterone; and cholesterol, which is an important structural component of biological membranes and a precursor of steroid hormones. - Other hydrophobic hormones include thyroid hormones and vitamin D. In order to be soluble in blood, hydrophobic ligands must bind to carrier proteins while they are being transported through the bloodstream. ii. **[Water-Soluble Ligands]** - Since water-soluble ligands are polar, they cannot pass through the plasma membrane unaided. - Sometimes they are too large to pass through the membrane at all. Instead, most water-soluble ligands bind to the extracellular domain of cell-surface receptors. - This group of ligands is quite diverse and includes small molecules, peptides, and proteins **[Propagation of the Signal]** - Once a water-soluble ligand binds to its receptor, the signal is transmitted through the membrane and into the cytoplasm. Continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors since internal receptors are able to enter the cell. - When a ligand binds to its receptor, conformational changes occur that affect the receptor's intracellular domain. These conformational changes lead to activation of the intracellular domain or its associated proteins. In some cases, binding of the ligand causes **dimerization** of the receptor, which means that two receptors bind to each other to form a stable complex called a dimer. A **dimer** is a chemical compound formed when two molecules (often identical) join together. - The binding of the receptors in this manner enables their intracellular domains to come into close contact and activate each other. **[Signaling Pathways and Signal Amplification]** - Although signaling molecules are often found at very low concentrations, they may produce profound effects. After the ligand binds to the cell-surface receptor, the activation of the receptor's intracellular components sets off a chain of events that is called a **signaling pathway** or a signaling cascade. - In a signaling pathway, second messengers, enzymes, and/or activated proteins activate other proteins or messengers. Each member of the pathway can activate thousands of the next member of the pathway in a process called **signal amplification**. Since the signal is amplified at each step, a very large response can be generated from a single receptor binding a ligand. - An example of a signaling pathway is Epidermal growth factor (EGF) is a signaling molecule that is involved in the regulation of cell growth, wound healing, and tissue repair. - The receptor for EGF (EGFR) is a tyrosine kinase. An activated kinase phosphorylates and activates many downstream molecules. When EGF binds to EGFR, a cascade of downstream phosphorylation events signals the cell to grow and divide. If EGFR is activated at inappropriate times, uncontrolled cell growth (cancer) may occur **[Methods of Intracellular Signaling]** - The induction of a signaling pathway depends on the modification of a cellular component by an enzyme. There are numerous enzymatic modifications that can occur to activate the next component of the pathway. The following are some of the more common events in intracellular signaling. **[Phosphorylation]** - One of the most common chemical modifications that occurs in signaling pathways is the addition of a phosphate group to a molecule in a process called **phosphorylation**. The phosphate can be added to a nucleotide such as GMP to form GDP or GTP. Phosphates are also often added to serine, threonine, and tyrosine residues of proteins, where they replace the hydroxyl group of the amino acid. The transfer of the phosphate is catalyzed by an enzyme called a kinase. Phosphorylation may activate or inactivate enzymes, and the reversal of phosphorylation, dephosphorylation, will reverse the effect. **[Second Messengers]** - Second messengers are small molecules that propagate a signal after it has been initiated by the binding of the signaling molecule to the receptor. These molecules help to spread a signal through the cytoplasm by altering the behavior of certain cellular proteins. - A second messenger utilized by many different cell types is cyclic AMP (cAMP). Cyclic AMP is synthesized by the enzyme adenylyl cyclase from ATP. The main role of cAMP in cells is to bind to and activate an enzyme called cAMP-dependent kinase (A-kinase). A-kinase regulates many vital metabolic pathways: It phosphorylates serine and threonine residues of its target proteins, activating them in the process. - A-kinase is found in many different types of cells, and the target proteins in each kind of cell are different. Another secondary messenger is Ca2+which can be released to flood the cell. **[Responses to the Signaling Pathway]** **Gene Expression** - Some signal transduction pathways regulate the transcription of RNA. Others regulate the translation of proteins. **Increase in Cellular Metabolism** - The activation of β-adrenergic receptors in muscle cells by adrenaline leads to an increase in cyclic AMP inside the cell. - Adrenaline is a hormone produced by the adrenal gland that readies the body for short-term emergencies. **Cell Growth** - Cell signaling pathways also play a major role in cell division. Cells do not normally divide unless they are stimulated by signals from other cells. - The ligands that promote cell growth are called growth factors. Most growth factors bind to cell-surface receptors that are linked to tyrosine kinases. **Cell Death** - When a cell is damaged, superfluous, or potentially dangerous to an organism, a cell can initiate a mechanism to trigger programmed cell death, or apoptosis. Apoptosis allows a cell to die in a controlled manner that prevents the release of potentially damaging molecules from inside the cell. - However, in some cases, such as a viral infection or uncontrolled cell division due to cancer, the cell's normal checks and balances fail. External signaling can also initiate apoptosis. For example, most normal animal cells have receptors that interact with the extracellular matrix, a network of glycoproteins that provides structural support for animal cells. - The binding of cellular receptors to the extracellular matrix initiates a signaling cascade within the cell. However, if the cell moves away from the extracellular matrix, the signaling ceases, and the cell undergoes apoptosis **[DEOXYRIBONUCLEIC ACID(DNA)]** - [DNA](https://www.thoughtco.com/dna-373454) is the genetic material that defines every cell. Before a [cell](https://www.thoughtco.com/facts-about-cells-373372) duplicates and is divided into new [daughter cells](https://www.thoughtco.com/daughter-cells-defined-4024745) through either [mitosis](https://www.thoughtco.com/stages-of-mitosis-373534) or [meiosis](https://www.thoughtco.com/stages-of-meiosis-373512), biomolecules and [organelles](https://www.thoughtco.com/organelles-meaning-373368) must be copied to be distributed among the cells. - DNA, found within the [nucleus](https://www.thoughtco.com/the-cell-nucleus-373362), must be replicated in order to ensure that each new cell receives the correct number of [chromosomes](https://www.thoughtco.com/chromosome-373462). The process of DNA duplication is called **DNA replication**. - Replication follows several steps that involve multiple [proteins](https://www.thoughtco.com/proteins-373564) called replication enzymes and [RNA](https://www.thoughtco.com/rna-373565). - In eukaryotic cells, such as [animal cells](https://www.thoughtco.com/all-about-animal-cells-373379) and [plant cells](https://www.thoughtco.com/what-is-a-plant-cell-373384), DNA replication occurs in the [S phase of interphase](https://www.thoughtco.com/stages-of-mitosis-373534) during the [cell cycle](https://www.thoughtco.com/understanding-the-cell-cycle-373391). The process of DNA replication is vital for cell growth, repair, and reproduction in organisms. **[DNA Structure]** - Deoxyribonucleic acid (DNA) is composed of four deoxy ribonucleotides, i.e., deoxyadenylate (A), deoxyguanylate (G), deoxycytidylate (C), and thymidylate (T). - These units are combined through 3\' to 5\' phosphodiester bonds to polymerise into a longchain. The nucleotide is formed by a combination of base + sugar + phosphoric acid. The 3\'-hydroxyl of one sugar is combined to the 5\'-hydroxyl of another sugar through a phosphate group. ![](media/image7.png) - In the DNA, the base sequence is of paramount importance. The genetic information is coded in the specific sequence of bases; if the base is altered, the information is also altered. The deoxyribose and phosphodiester linkages are the same in all the repeating nucleotides. - Therefore, the message will be conveyed, even if the base sequences alone are mentioned as shown: 5\'P\--Thymine\--Cytosine-Adenine-3\'OH Or, 5\'\-\-\-\-\--T\--C\--A\-\--3\' **[Polarity of DNA molecule]** - DNA (deoxyribonucleic acid) is a double-stranded molecule with a specific polarity. Each DNA strand consists of a linear chain of nucleotides, and these nucleotides have both a 5\' end and a 3\' end, which creates the polarity in the DNA molecule. The key features of the polarity of DNA are as follows: - **5\' End:** The 5\' end of a DNA strand is the end where the fifth carbon atom in the deoxyribose sugar of the nucleotide is located. The carbon atoms in the deoxyribose sugar are numbered from 1\' to 5\'. At the 5\' end, the phosphate group (PO~4~) of one nucleotide is attached to the 5\' carbon of the deoxyribose sugar of the adjacent nucleotide in the same strand. This forms a phosphodiester bond. - **3\' End:** The 3\' end of a DNA strand is the end where the third carbon atom in the deoxyribose sugar of the nucleotide is located. The 3\' carbon has a hydroxyl group (OH) attached to it. The hydroxyl group at the 3\' end is available for forming phosphodiester bonds with the phosphate group at the 5\' end of the next nucleotide in the same strand. - Because of this arrangement, the DNA molecule has directionality. The two strands of DNA run in opposite directions, creating an antiparallel structure. The 5\' end of one strand is paired with the 3\' end of the complementary strand. - This polarity and antiparallel structure are crucial for the process of DNA replication and the transcription of DNA into RNA. DNA polymerases, the enzymes responsible for replicating DNA, can only add new nucleotides to the 3\' end of a growing DNA strand. - Therefore, **replication proceeds in the 5\' to 3\' direction on one strand (the leading strand) and in the opposite direction on the other strand (the lagging strand), resulting in the formation of two new DNA strands that are complementary to the original strands.** Understanding the polarity of DNA is fundamental to understanding these biological processes and how genetic information is maintained and transmitted. [ ] **[Replication process]** **[Step 1: Replication Fork Formation]** - Before DNA can be replicated, the double stranded molecule must be "unzipped" into two single strands. - DNA has four bases called **adenine (A)**, **thymine (T)**, **cytosine (C)** and **guanine (G)** that form pairs between the two strands. Adenine only pairs with thymine and cytosine only binds with guanine. - In order to unwind DNA, these interactions between base pairs must be broken. This is performed by an enzyme known as **DNA helicase**. - DNA **helicase** disrupts the [**hydrogen bonding**](https://www.thoughtco.com/definition-of-hydrogen-bond-605872) between base pairs to separate the strands into a Y shape known as the **replication fork**. This area will be the template for replication to begin. - **[DNA](https://www.thoughtco.com/dna-373454) **is directional in both strands, signified by a 5\' and 3\' end. This notation signifies which side group is attached the DNA backbone. The **5\' end **has a phosphate (P) group attached, while the **3\' end** has a hydroxyl (OH) group attached. - This directionality is important for replication as it only progresses in the 5\' to 3\' direction. - However, the replication fork is bi-directional; one strand is oriented in the 3\' to 5\' direction **(leading strand)** while the other is oriented 5\' to 3\' **(lagging strand)**. - The two sides are therefore replicated with two different processes to accommodate the directional difference. **[Step 2: Primer Binding]** - The leading strand is the simplest to replicate. Once the DNA strands have been separated, a short piece of [**RNA**](https://www.thoughtco.com/rna-373565) called a **primer** binds to the 3\' end of the strand. - The primer always binds as the starting point for replication. Primers are generated by the enzyme **DNA primase**. **[Step 3: Elongation]** - Enzymes known as **DNA polymerases** are responsible creating the new strand by a process called **elongation**. There are five different known types of DNA polymerases in** [bacteria](https://www.thoughtco.com/bacteria-friend-or-foe-372431)** and **[human cells](https://www.thoughtco.com/types-of-cells-in-the-body-373388).** - In bacteria such as E. coli, **polymerase III** is the main replication enzyme, while polymerase I, II, IV and V are responsible for error checking and repair. DNA polymerase III binds to the strand at the site of the primer and begins adding new base pairs complementary to the strand during replication. - In eukaryotic cells, polymerases alpha, delta, and epsilon are the primary polymerases involved in DNA replication. Because replication proceeds in the 5\' to 3\' direction on the leading strand, the newly formed strand is continuous. - The **lagging strand** begins replication by binding with multiple primers. Each primer is only several bases apart. DNA polymerase then adds pieces of DNA, called **Okazaki fragments**, to the strand between primers. - This process of replication is discontinuous as the newly created fragments are disjointed. **[Step 4: Termination]** - Once both the continuous and discontinuous strands are formed, an enzyme called **exonuclease** removes all RNA primers from the original strands. These primers are then replaced with appropriate bases. - Another exonuclease "proofreads" the newly formed DNA to check, remove and replace any errors. Another enzyme called **DNA ligase** joins Okazaki fragments together forming a single unified strand. - The ends of the linear DNA present a problem as DNA polymerase can only add nucleotides in the 5′ to 3′ direction. The ends of the parent strands consist of repeated DNA sequences called telomeres. - Telomeres act as protective caps at the end of chromosomes to prevent nearby chromosomes from fusing. A special type of DNA polymerase enzyme called **telomerase** catalyses the synthesis of telomere sequences at the ends of the DNA. - Once completed, the parent strand and its complementary DNA strand coils into the familiar [double helix](https://www.thoughtco.com/double-helix-373302) shape. In the end, replication produces two [DNA molecules](https://www.thoughtco.com/dna-373454), each with one strand from the parent molecule and one new strand. **[RNA (Protein Synthesis) ]** - This amazing artwork shows a process that takes place in the cells of all living things: the production of proteins. This process is called **protein synthesis**, and it** **actually consists of two processes **transcription** and **translation**. In eukaryotic cells, transcription takes place in the nucleus. During transcription, DNA is used as a template to make a molecule of **messenger RNA (mRNA).** - The molecule of **mRNA** then leaves the nucleus and goes to a ribosome in the cytoplasm, where translation occurs. - During translation, the genetic code in mRNA is read and used to make a protein. These two processes are summed up by the central dogma of molecular biology: **DNA → RNA → Protein**. **[Medical significance of DNA Replication]** **Cell Growth and Repair:** DNA replication is essential for cell growth, tissue repair, and the development of new cells. It is particularly crucial during periods of rapid cell division, such as in embryonic development and the regeneration of damaged or injured tissues. **Prevention of Genetic Mutations:** Accurate DNA replication is critical for preventing mutations. Errors during replication can result in mutations, which can lead to various genetic disorders and diseases, including cancer. Many DNA repair mechanisms are in place to correct errors that occur during replication. **Cancer:** Dysregulation of DNA replication can lead to uncontrolled cell growth and is a hallmark of cancer. Understanding the mechanisms involved in DNA replication and how they can go awry is essential for developing cancer treatments and therapies. **Fertility and Reproduction:** DNA replication is fundamental in processes related to fertility and reproduction. Errors in replication can lead to infertility and developmental abnormalities. **Diagnosis and Genetic Testing**: The ability to replicate DNA has allowed the development of various diagnostic tests, such as polymerase chain reaction (PCR), which amplifies specific DNA sequences for analysis. This technology is used in genetic testing, forensic analysis, and the diagnosis of infectious diseases. **Pharmacology and Drug Development:** Many drugs and therapies target the DNA replication process, particularly in the context of chemotherapy. Medications that inhibit DNA replication are used to target rapidly dividing cancer cells. **Viral Replication:** Understanding DNA replication is crucial for the development of antiviral drugs. Certain antiviral medications target the replication processes of viruses that use DNA as their genetic material, such as herpesviruses and retroviruses (e.g., HIV). **Genomic Medicine:** Advances in genomics and personalized medicine rely on a deep understanding of DNA replication. This knowledge is used in the diagnosis and treatment of genetic diseases and in tailoring medical interventions to an individual\'s genetic makeup. **Prenatal Testing:** DNA replication and analysis play a crucial role in prenatal testing for genetic abnormalities, such as amniocentesis and chorionic villus sampling. These tests assess the DNA of a developing fetus to detect genetic disorders. **Gene Therapy:** Gene therapy, aimed at correcting genetic diseases by introducing healthy genes, often involves modifying DNA. Understanding DNA replication and the mechanisms of gene insertion is crucial for the success of gene therapy **[TRANSCRIPTION]** - **Transcription** is the first part of the central dogma of molecular biology: **DNA → RNA**. - It is the transfer of genetic instructions in DNA to mRNA. During transcription, a strand of mRNA is made to complement a strand of DNA. You can see how this happens in the diagram [below](https://flexbooks.ck12.org/cbook/ck-12-college-human-biology-flexbook-2.0/section/5.6/primary/lesson/protein-synthesis-chumbio/#x-ck12-MjAxNDEyMjkxNDE5ODY1MzQwNzU3NDYyXzY4NWI2ZWI0OTNkNWIxMWFiYTlmN2Y5Y2U0NzA5YzdlLTIwMTQxMjI5MTQxOTg2Njg0MjUwMTA3NA..). https://dr282zn36sxxg.cloudfront.net/datastreams/f-d%3Acd98251f19b9764ccc780736107d817a73a7e7ed02322baa3e9a4ece%2BIMAGE\_THUMB\_POSTCARD\_TINY%2BIMAGE\_THUMB\_POSTCARD\_TINY.1 - scription uses the sequence of bases in a strand of DNA to make a complementary strand of mRNA. Triplets are groups of three successive nucleotide bases in DNA. Codons are complementary groups of bases in mRNA. **[Steps of Transcription]** 1. **Initiation:** - Transcription begins with the recognition of a specific DNA sequence called the promoter by RNA polymerase; an enzyme responsible for RNA synthesis. - In prokaryotes, RNA polymerase directly binds to the promoter region of the DNA, initiating transcription. - In eukaryotes, transcription initiation is more complex. RNA polymerase II, which transcribes protein-coding genes, requires additional proteins called transcription factors to recognize and bind to the promoter. 2. **Formation of the Transcription Bubble:** - Once the RNA polymerase-promoter complex forms, it causes a local unwinding of the DNA double helix, creating a region known as the transcription bubble. - Within the transcription bubble, one DNA strand, known as the template strand, serves as the template for RNA synthesis, while the complementary DNA strand (the non-template strand) is not used. 3. **Elongation:** - During the elongation phase of transcription, RNA polymerase moves along the template strand, synthesizing an RNA molecule complementary to the template. - Nucleoside triphosphates (NTPs) containing adenine (A), cytosine (C), guanine (G), and uracil (U) are added to the growing RNA chain. - The RNA molecule grows in the 5\' to 3\' direction, complementary to the template strand. 4. **Termination:** - Transcription terminates when RNA polymerase encounters a termination signal on the DNA. - In prokaryotes, there are two main types of termination: Rho-independent and Rho-dependent. Rho-independent termination occurs when a specific DNA sequence in the RNA transcript forms a hairpin structure, leading to transcription termination. Rho-dependent termination involves the action of the Rho protein. - In eukaryotes, termination is more complex and often involves the cleavage and polyadenylation of the RNA transcript. 5. **[Processing (Eukaryotes Only):]** - In eukaryotes, the initial RNA transcript, called pre-mRNA, undergoes several modifications before becoming mature mRNA. These include capping, splicing, and polyadenylation. - The 5\' end of the pre-mRNA receives a 5\' cap, consisting of a modified guanosine nucleotide, which is important for mRNA stability and translation initiation. - Introns (non-coding regions) are removed from the pre-mRNA through a process called splicing, leaving only the exons (coding regions). - A poly-A tail is added to the 3\' end of the pre-mRNA, which is crucial for mRNA stability and transport from the nucleus to the cytoplasm. - The end result of transcription is a mature mRNA molecule that carries the genetic information from the DNA to the ribosomes, where it serves as a template for protein synthesis during translation. Different types of RNA, such as transfer RNA (tRNA) and ribosomal RNA (rRNA), are also transcribed and play essential roles in protein synthesis and various cellular processes ![https://dr282zn36sxxg.cloudfront.net/datastreams/f-d%3Afdf443db9c5aa657ab8bdd54ac0348efb755e7a176ea313dbd700ec4%2BIMAGE\_THUMB\_POSTCARD\_TINY%2BIMAGE\_THUMB\_POSTCARD\_TINY.1](media/image9.png) **[Processing mRNA]** - In eukaryotes, the new mRNA is not yet ready for translation. At this stage, it is called pre-mRNA, and it must go through more processing before it leaves the nucleus as mature mRNA. - The processing may include splicing, editing, and polyadenylation. These processes modify the mRNA in various ways. Such modifications allow a single gene to be used to make more than one protein. - **Splicing** removes introns from mRNA. **Introns** are regions that do not code for the protein. The remaining mRNA consists only of regions called **exons** that do code for the protein. The ribonucleoproteins in the diagram are small proteins in the nucleus that contain RNA and are needed for the splicing process. - **Editing** changes some of the nucleotides in mRNA. For example, a human protein called APOB, which helps transport lipids in the blood, has two different forms because of editing. One form is smaller than the other because editing adds an earlier stop signal in mRNA. - **Polyadenylation** adds a "tail" to the mRNA. The tail consists of a string of As (adenine bases). It signals the end of mRNA. It is also involved in exporting mRNA from the nucleus, and it protects mRNA from enzymes that might break it down. https://dr282zn36sxxg.cloudfront.net/datastreams/f-d%3Ad2920bf9f495c4bd2da0641a94d60136f7d883dfc7692f455741abbe%2BIMAGE\_THUMB\_POSTCARD\_TINY%2BIMAGE\_THUMB\_POSTCARD\_TINY.1 - Splicing. Splicing removes introns from **mRNA.** **[Translation]** - **Translation** is the second part of the central dogma of molecular biology: **RNA → Protein**. It is the process in which the genetic code in **mRNA** is read to make a protein. - After **mRNA** leaves the nucleus, it moves to a ribosome, which consists of **rRNA** and proteins. The ribosome reads the sequence of codons in **mRNA**, and molecules of **tRNA **bring amino acids to the **ribosome** in the correct sequence. - To understand the role of **tRNA**, you need to know more about its structure. Each **tRNA** molecule has an anticodon for the **amino [acid](https://www.ck12.org/c/chemistry/acid?referrer=crossref)** it carries. - An **anticodon** is complementary to the codon for an amino acid. For example, the amino acid **lysine** has the codon **AAG,** so the anticodon is **UUC.** Therefore, **lysine** would be carried by a **tRNA** molecule with the anticodon **UUC.** - Wherever the codon **AAG** appears in mRNA, a **UUC** anticodon of **tRNA temporarily** binds. While bound to **mRNA,** **tRNA** gives up its amino acid. With the help of **rRNA**, bonds form between the amino acids as they are brought one by one to the ribosome, creating a polypeptide chain. The chain of amino acids keeps growing until a stop codon is reached. **[STRUCTURE, PROPERTIES AND FUNCTIONS OF;]** A. **[Proteins]** - Proteins are complex macromolecules that play critical roles in almost all biological processes. They are the most abundant biological macromolecules, occurring in all cells are composed of amino acids, which are their building blocks (polymers of amino acids covalently linked by the peptide bonds). The building blocks of proteins are the twenty naturally occurring **amino acids**. - The structure, properties, and functions of proteins are closely interconnected and determine their role in the cell and overall **biological functions**. **[Structure of Proteins:]** - Proteins have four levels of structural organization, each contributing to their overall shape and function. i. **[Primary Structure]** - The primary structure of a protein consists of the amino acid sequence along the polypeptide chain. - Amino acids are joined by peptide bonds. - Because there are no dissociable protons in peptide bonds, the charges on a polypeptide chain are due only to the N-terminal amino group, the C-terminal carboxyl group, and the side chains on amino acid residues. - The primary structure determines the further levels of organization of protein molecules. ![](media/image11.png) ii. **[Secondary Structure]** - The secondary structure includes various types of local conformations in which the atoms of the side chains are not involved. - Secondary structures are formed by a regular repeating pattern of hydrogen bond formation between backbone atoms. - The secondary structure involves α-helices, β-sheets, and other types of folding patterns that occur due to a regular repeating pattern of hydrogen bond formation. - The secondary structure of protein could be: a. **Alpha-helix & Beta-helix** - The α-helix is a right-handed coiled strand. - The side-chain substituents of the amino acid groups in an α-helix extend to the outside. - Hydrogen bonds form between the oxygen of the C=O of each peptide bond in the strand and the hydrogen of the N-H group of the peptide bond four amino acids below it in the helix. - The side-chain substituents of the amino acids fit in beside the N-H groups. - The hydrogen bonding in a **ß-sheet** is between strands (inter-strand) rather than within strands (intra-strand). - The sheet conformation consists of pairs of strands lying side-by-side. - The carbonyl oxygens in one strand hydrogen bond with the amino hydrogens of the adjacent strand. - The two strands can be either parallel or anti-parallel depending on whether the strand directions (N-terminus to C-terminus) are the same or opposite. - The anti-parallel ß-sheet is more stable due to the more well-aligned hydrogen bonds. iii. **[Tertiary Structure]** - Tertiary structure of a protein refers to its overall three-dimensional conformation. - The types of interactions between amino acid residues that produce the three-dimensional shape of a protein include hydrophobic interactions, electrostatic interactions, and hydrogen bonds, all of which are noncovalent. - Covalent disulfide bonds also occur. - It is produced by interactions between amino acid residues that may be located at a considerable distance from each other in the primary sequence of the polypeptide chain. - Hydrophobic amino acid residues tend to collect in the interior of globular proteins, where they exclude water, whereas hydrophilic residues are usually found on the surface, where they interact with water. iv. **[Quaternary Structure]** - Quaternary structure refers to the interaction of one or more subunits to form a functional protein, using the same forces that stabilize the tertiary structure. - It is the spatial arrangement of subunits in a protein that consists of more than one polypeptide chain ![](media/image13.png) [**Properties of Proteins:** ] - Proteins exhibit several important properties that arise from their structure: - **Specificity:** Proteins have unique shapes and chemical properties that enable them to interact selectively with other molecules, such as enzymes binding to substrates. - **Flexibility:** While proteins have stable three-dimensional structures, they also possess a degree of flexibility that allows them to adapt to different functional states and interactions. - **Solubility:** Proteins can vary in their solubility, being either water-soluble (hydrophilic) or insoluble (hydrophobic), based on the distribution of polar and nonpolar amino acids. - **Denaturation:** External factors like heat, pH changes, or certain chemicals can disrupt a protein\'s structure, causing it to lose its function. This is known as denaturation. **3. Functions of Proteins:** Proteins have diverse functions in living organisms: - **Enzymes:** Proteins act as biological catalysts, speeding up chemical reactions in cells. Enzymes play a crucial role in metabolism, DNA replication, and many other cellular processes. - **Structural Support:** Proteins like collagen and keratin provide structural support to cells and tissues. Collagen, for instance, is a major component of connective tissues and gives strength to skin, tendons, and bones. - **Transport:** Proteins like hemoglobin transport oxygen in the blood, while other transport proteins move molecules across cell membranes. - **Cell Signaling:** Receptor proteins on cell surfaces recognize and bind to specific signaling molecules, transmitting information into the cell. - **Immune Response:** Antibodies are proteins produced by the immune system that recognize and neutralize foreign substances (antigens) like bacteria and viruses. - **Movement:** Proteins such as actin and myosin are involved in muscle contraction and cell movement. - **Regulation:** Regulatory proteins control various processes in the cell, including gene expression and cell cycle progression **[Water- Definition, Structure, Characteristics, Properties, Functions]** Water- Definition, Structure, Characteristics, Properties, Functions **Water Definition:** - Water is an inorganic liquid chemical that is colourless, odourless, tasteless that makes up most of the Earth's hydrosphere and the fluids in the body of all living beings. - Water is an extremely important component for the existence of life as it is vital for all biological processes. It doesn't, however, have any calorific value or nutritional value. - Water is in a liquid state at standard atmospheric temperature and pressure. - It occupies 71% of the total land on Earth and about 70% of total body weight in humans. - The amount of water on Earth is maintained by a continuous movement of water from the ground to the atmosphere and back, called the water cycle. - Water is also important for various chemical processes as it is a universal solvent. **[Structure of Water]** - The chemical formula for water is H~2~O which indicates that a single molecule of water is made up of two hydrogen atoms and one oxygen atom. - The atoms in a water molecule are connected to each other by polar covalent bonds. The molecule in itself is electrically neutral but polar with negative and positive charges localized in different areas. **In the gaseous phase** - In a water molecule, the s and p orbitals of the valence shell are sp^3^ hybridized to form four sp^3^ hybrid orbitals oriented tetrahedrally around the oxygen atom. - The two of the hybrid orbitals are singly occupied, while the lone pairs of the electrons occupy the other two. - Each single occupied sp^3 ^orbital overlaps with the half-filled orbital of the H atom. - As a result, an oxygen atom is bonded to the two hydrogen atoms by two O-H covalent bonds, and there are two lone pairs of electrons on the oxygen atom. - The most stable arrangement of the atoms is the one where they are the farthest. The angle between the O-H bonds is around 104° rather than a perfect tetrahedron (109°) due to the repulsion between the lone pairs. - Thus, the structure of the water molecule is an angular of bent structure. - The molecule of water is polar because oxygen is more electronegative than hydrogen. The oxygen atom thus attracts the shared electrons towards itself. - As a result, a partial negative charge is developed on the oxygen atom while the hydrogen atom develops a partial positive charge. **In the liquid phase** - In the liquid phase, water molecules are held together by intermolecular hydrogen bonds. - A single water molecule is capable of forming four hydrogen bonds as it can form two bonds with the lone pair on oxygen and donate two electrons on hydrogen. - In water, the formation of four hydrogen bonds results in an intermolecular tetrahedral structure forming an open structure and three-dimensional bonding network. **In solid phase** - The solid form of water is ice, which can exist in different crystalline forms depending on the conditions for the freezing of water. - In the regular hexagonal ice, each oxygen atom is tetrahedrally surrounded by four other oxygen atoms, whereas one hydrogen atom lies in between each pair of oxygen. - Thus, each hydrogen atom is covalently bonded to one oxygen atom and linked to another oxygen atom by a hydrogen bond. - This arrangement causes the packing of atoms with large open spaces which results in the decrease in density of ice as compared to liquid water. - When ice melts, some of the hydrogen bonds are broken, and the water molecules become more tightly packed. **[Hydrogen bonding in water]** - Due to polarity in water molecules, they are capable of attracting each other. These interactions are weak attractions called hydrogen bonds. - Hydrogen bond in water is a weak interaction between the partially positive hydrogen atom and a partially negative oxygen atom. - Hydrogen bonding in water is intermolecular and occurs between two atoms of two different molecules. - A single water molecule is capable of forming four hydrogen bonds as it can form two bonds with the lone pair on oxygen and donate two electrons on hydrogen. - In water, the formation of four hydrogen bonds results in an intermolecular tetrahedral structure forming an open structure and three-dimensional bonding network. - The structure formed after hydrogen bonding results in the collective ground state of liquid water to have energy lower than the ground state in single gaseous molecules. - This creates a stable structure of water molecules in liquid water. - Hydrogen bond formed in water is a weak bond, and its strength is one-twentieth of that of the O-H covalent bond. - The lifetime of these bonds is also very short, and they are continuously broken and formed within short periods of time. Thus, a dynamic equilibrium is maintained in liquid water. - Similarly, all water molecules in liquid water have at least one hydrogen bond with a neighbouring water molecule with effectively no free water molecules. - Hydrogen bonding in water holds water molecules about 15% closer than if only Van der Waals interactions existed. - However, hydrogen bonding in water is directional, which restricts the number of neigh boring water molecules to just about four than the larger numbers in other liquids. **[Characteristics/ Properties of water]** **[Physical properties of water]** - Pure water is a transparent, colourless, odourless liquid that readily picks up the flavour of any substance dissolved in it. - The freezing point, boiling point, enthalpy of fusion, and enthalpy of vaporization of water is higher compared to the hydrides of other members of the same group due to the intermolecular hydrogen bonds between the molecules. - Water has a high dipole moment which makes it an ideal medium for the dissolution of a wide variety of compounds. - The high specific heat capacity of water enables it to absorb the heat of various biochemical and physiological reactions, going on inside the body, with the minimum rise of temperature. - Water is a poor conductor of heat and electricity, but the addition of a small quantity of an acid or an alkali makes it electrically conducting. **[The solvent action of water]** - Water is also called a universal solvent because of its ability to dissolve a larger variety of substances. - This ability is due to the intensive hydrogen bonding and polarity of water molecules. - The polarity of water causes water to behave differently with polar and non-polar compounds. - Polar molecules of water can form weak electrostatic interactions with other polar molecules and ions. - Thus, the polar molecules and ions interact with the partially positive and partially negative ends of water, with positive charges attracting negative charges. - - - **[High specific heat capacity]** - By virtue of intensive hydrogen bonding, water has a very high specific heat capacity and high heat of vaporization. - These properties allow water to moderate the climate and temperature of Earth by buffering large fluctuations in temperatures. - A similar process occurs within the body where water prevents the rapid rise in body temperature as a result of various biochemical reactions. - The latent heat of fusion and vaporization of water is also high, which prevents the melting of ice glaciers and drift ice. **[Anomalous expansion of water]** - Anomalous expansion of water is an abnormal property of water where water expands instead of contracting when the temperature goes from 4°C to 0°C. - Thus, the density of water is maximum at 4°C and decreases as the temperature goes down. - This property of water results because the water molecules in freezing state are held together by H-O attraction rather than O-O attraction. - But because the H-O interaction is not as tight as the O-O interaction, a little expansion of water is