Medical Biochemistry Lecture One 2024-2025 PDF

University of Zakho College of Medicine Introduction to Biochemistry & Cell Medical Biochemistry Dr Lina Yousif Mohammed Email: [email protected] First Seme...

University of Zakho College of Medicine Introduction to Biochemistry & Cell Medical Biochemistry Dr Lina Yousif Mohammed Email: [email protected] First Semester_ Academic Year: 2024_2025  Session One: Introduction to Biochemistry Aims The course aims to provide a basic understanding of the core principles and topics of Biochemistry and their experimental basis. To enable students to acquire a specialized knowledge and understanding of selected aspects by means of branch lecture series. Learning Outcomes By the end of the session, the students should be able to demonstrate advanced knowledge and understanding in the following core areas. 1. Students will understand the structures and purposes of basic components of prokaryotic and eukaryotic cells, especially macromolecules, membranes, and organelles. 2. Students will understand how these cellular components are used to generate and utilize energy in cells. 3. Students will understand the cellular components underlying mitotic cell division. What is biochemistry? Biochemistry: sometimes called biological chemistry, is the study of chemical processes within and relating to living organisms. Biochemical processes give rise to the complexity of life. Biochemistry can be divided in three fields; Molecular genetics. Protein science and, Metabolism. Biochemistry focuses : understanding how biological molecules give rise to the processes that occur within living cells and between cells, which in turn relates greatly to the study and understanding of tissues, organs, and organism structure and function. What Types of Molecules Do Biochemists Study? Biochemists deal with the structures, functions and interactions of biological macromolecules, such as proteins, nucleic acids, carbohydrates and lipids, which provide the structure of cells and perform many of the functions associated with life. Introduction to the cells The word cell comes from the Latin cellula, meaning "a small room". The study of cells is called cytology. Robert Hooke was the first scientist to use the word cell. Robert Brown discovered the nucleus in 1833. Theodor Schwann discovered that animals were made of cells in 1838. Cell Theory All living things are made up of cells. Cells are the smallest working units of all living things. All cells come from preexisting cells through cell division.  Examples of Cells Amoeba Proteus Plant Stem Bacteria Red Blood Cell Nerve Cell A cell is the smallest unit that is capable of performing life functions. Types of cells: The biological universe consists of two types of cells: Prokaryotic cells: consist of a single closed compartment that is surrounded by the plasma membrane, lacks a defined nucleus, and has a relatively simple internal organization. Examples: Bacteria and Blue-green algae. Eukaryotic cells: unlike prokaryotic cells, contain a defined membrane-bound nucleus and extensive internal membranes that enclose other compartments. The region of the cell lying between the plasma membrane and the nucleus is the cytoplasm, comprising the cytosol (aqueous phase) and the organelles. Eukaryotes comprise all members of the plant and animal kingdoms, including the fungi, which exist in both multicellular forms (molds) and unicellular forms (yeasts). Typical” Plant Cell Typical” Animal Cell Biological Membranes Membranes are the outer boundary of individual cells and of certain organelles. Plasma membranes are the selectively permeable outermost structures of cells that separate the interior of the cell from the environment. Certain molecules are permitted to enter and exit the cell through transport across the plasma membrane.  Components of biological membranes: All cell membranes are composed of the same materials: 1. Lipids Lipids are the most abundant type of macromolecule present. Plasma and organelle membranes contain between 40% and 80% lipid. There are three types of lipids are found: A. Phospholipids: The most abundant of the membrane lipids are the phospholipids. They are polar, ionic compounds that are amphipathic (have both hydrophilic and hydrophobic components). The hydrophilic or polar portion is in the “head group”. Within the head group is the phosphate and an alcohol that is attached to it. The hydrophobic portion of the phospholipid is a long, hydrocarbon (structure of carbons and hydrogens) fatty acid tail. B. Cholesterol: is an amphipathic molecule, which contains a polar hydroxyl group as well as a hydrophobic steroid ring and attached hydrocarbon. Cholesterol is dispersed throughout cell membranes, intercalating (insert) between phospholipids. Its polar hydroxyl group is near the polar head group of the phospholipids while the steroid ring and hydrocarbon tails of cholesterol are oriented parallel to those of the phospholipids. Cholesterol fits into the spaces created by the kinks of the unsaturated fatty acid tails, decreasing the ability of the fatty acids to undergo motion and therefore causing stiffening and strengthening of the membrane. C. Glycolipids: Lipids with attached carbohydrate (sugars), glycolipids are found in cell membranes in lower concentration than phospholipids and cholesterol. The carbohydrate portion is always oriented toward the outside of the cell, projecting into the environment. Glycolipids help to form the carbohydrate coat observed on cells and are involved in cell- to-cell interactions. 2. Proteins: While lipids form the main structure of the membrane, proteins are largely responsible for many biological functions of the membrane. The types of proteins within a plasma membrane vary depending on the cell type. However, all membrane proteins are associated with membrane in one of three main ways: 2.1 Transmembrane proteins: They are embedded within the lipid bilayer of the membrane with structures that extend from the environment into the cytosol. All transmembrane proteins contain both hydrophilic and hydrophobic components. These proteins are oriented with their hydrophilic portions in contact with the aqueous exterior environment and with the cytosol and their hydrophobic portions in contact with the fatty acid tails of the phospholipids. 2.2 Lipid-anchored proteins: They are attached covalently to a portion of a lipid without entering the core portion of the bilayer of the membrane. Both transmembrane and lipid- anchored proteins are integral membrane proteins since they can only be removed from a membrane by disrupting the entire membrane structure. 2.3 Peripheral membrane proteins: These proteins are located on the cytosolic side of the membrane and are only indirectly attached to the lipid of the membrane; they bind to other proteins that are attached to the lipids. Cell wall In bacteria and plant cells the outermost cell cover, present outside the plasma membrane is the cell wall. Structure Outermost non-living, layer present in all plant cells. Secreted by the cell itself. In plant, made of cellulose but may also contain other chemical substance such as pectin and lignin. Functions  The cell wall protects the delicate inner parts of the cell.  Being rigid, it gives shape to the cell.  It freely allows the passage of water and other chemicals into and out of the cells. Transport across membranes Transport of small molecules (such as glucose, amino acids, water, mineral ions etc) can be transported across the plasma membrane by any one of the following three methods: Diffusion: molecules of substances move from their region of higher concentration to their region of lower concentration. This does not require energy. Example: absorption of glucose in a cell. Osmosis: movement of water molecules from the region of their higher concentration to the region of their lower concentration through a semipermeable membrane. There is no expenditure (spending) of energy in osmosis. This kind of movement is along concentration gradient. Active Transport: When the direction of movement of a certain molecule is opposite that of diffusion i.e. from region of their lower concentration towards the region of their higher concentration, it would require an “active effort” by the cell for which energy is needed. This energy is provided by ATP (adenosine triphosphate). The active transport may also be through a carrier molecule. Transport of large molecules (bulk transport) During bulk transport the membrane changes its form and shape. It occurs in two ways: Endocytosis (taking the substance in). Exocytosis (passing the substance out). Endocytosis is of two types: 1. phagocytosis 2. pinocytosis  Phagocytosis 1. Intake of solid particles. 2. Membrane folds out going round the particles, forming a cavity and thus engulfing (eat) the particle. Pinocytosis 1. Intake of fluid droplets. 2. Membrane folds in and forms a cup like structure sucks in droplets.  Organelles Organelles are complex intracellular locations where processes necessary for eukaryotic cellular life occur. Most organelles are membrane-enclosed structures. Their membranes are composed of the same components as plasma membranes that form the outer boundaries of cells. Together with the cytosol (liquid portion of the cytoskeleton), the organelles help to form the cytoplasm, composed of all materials contained within the boundaries of the plasma membrane. Organelles do not float freely within the cytosol but are interconnected and joined by the framework established by proteins of the cytoskeleton. Each organelle carries out a specific function. Cells Organelles 1. Nucleus All eukaryotic cells except mature erythrocytes (red blood cells) contain a nucleus where the cell’s genomic DNA resides. The outermost structure of the nucleus is the nuclear envelope. This is a double- layered phospholipid membrane with nuclear pores to permit transfer of materials between the nucleus and the cytosol. The interior of the nucleus contains the nucleoplasm (the fluid in which the DNAs are found). Within the nucleus there is a sub-organelle called the nucleolus. The nucleolus is the site of ribosome production. 2. Ribosomes: are the cellular machinery for protein synthesis. They are composed of proteins and ribosomal RNA (rRNA) with approximately 40% being protein and 60% rRNA. Ribosomes are found within the cytosol either free or bound to the endoplasmic reticulum. 3. Endoplasmic reticulum (ER): ER is often observed to surround the nucleus. The outer layer of the nuclear envelope is actually contiguous (sharing) with the ER. The ER forms a maze (network) of membrane- enclosed, interconnected spaces that constitute the ER lumen regions of ER where ribosomes are bound to the outer membrane are called rough endoplasmic reticulum (rER). Bound ribosomes and the associated ER are involved in the production and modification of proteins.  Smooth endoplasmic reticulum (sER) Refers to the regions of ER without attached ribosomes. Both rER and sER function in the glycosylation (addition of carbohydrate) of proteins and in the synthesis of lipids. 4. Golgi complex: It appears as flat, stacked, membranous sacs. Three regions are described within the Golgi complex: the cis, which is closest to the ER; the medial; and the trans Golgi, which is near the plasma membrane. Each region is responsible for performing distinct modifications to the newly synthesized proteins, such as: Glycosylation: addition of carbohydrate. Phosphorylation: addition of phosphate. Proteolysis: enzyme-mediated breakdown of protein. 5. Mitochondrion and Chloroplast: Energy transformer 5.1 Mitochondria:Complex organelles, mitochondria have several important functions in eukaryotic cells. Their unique membranes are used to generate ATP (greatly increasing the energy yield from the breakdown of carbohydrates and lipids). The very survival of individual cells depends on the integrity of their mitochondria. One characteristic feature of mitochondria is the double phospholipid bilayer membranes that form the outer boundary of the organelle. The inner mitochondrial membrane forms folded structures called cristae that protrude into the mitochondrial lumen known as the mitochondrial matrix.  5.2 Plastids are found only in a plant cell. They may be colourless or with colour. Based on this fact, there are three types of plastids. Leucoplast: white or colourless Chromoplast : blue, red, yellow etc. Chloroplast : green Chloroplasts are the energy trappers (found only in green plant cells) while Mitochondria (found in plant and animal cells) are the energy releasers. Found in all green plant cells in the cytoplasm. Number 1 to 1008 Shape Usually disc-shaped or spherical as in most plants around you. Structure: Wall made of double membrane i.e. outer membrane and inner membrane numerous stack-like (piles) groups or grana are interconnected by lamellae. Sac like structures called thylakoids Placed one above the other constitute granum. Inside of the chloroplast is filled with a fluid medium called stoma. Function: chloroplasts are the seat of photosynthesis (production of sugar, from carbon dioxide and water in the presence of sunlight). 6. The microbodies (tiny but important) These are small sac-like structures bounded by their membranes. These are of different kinds like lysosomes, peroxisomes and glyoxysomes. 6.1 Lysosomes: Are membrane-enclosed organelles of various sizes that have an acidic internal pH (pH 5). Lysosomes contain potent enzymes known collectively as acid hydrolases. They function within the acidic environment of lysosomes to hydrolyze or break down macromolecules (proteins, nucleic acids, carbohydrates and lipids). Nonfunctional macromolecules build up to toxic levels if they are not degraded within lysosomes and properly recycled for reuse within the cell. In addition, lysosomal enzymes also degrade materials that have been taken up by the cell through endocytosis or phagocytosis. 6.2. Peroxisomes: Resemble lysosomes in size and in structure. They have single membranes enclosing them and contain hydrolytic enzymes.  It helps in: Break down of fatty acids and purines (AMP and GMP). Detoxification of hydrogen peroxide (a toxic by-product of many metabolic reactions). Synthesis of myelin (the substance that forms a protective sheath around many neurons). In liver cells, peroxisomes participate in cholesterol and bile acid synthesis. 6.3 Glyoxysomes The microbodies present in plant cells and morphologically similar to peroxisomes. Found in the cell of yeast and certain fungi and oil rich seeds in plants. Functionally they contain enzyme of fatty acid metabolism involved in the conversion of lipids to carbohydrates during germination. 7. Cilia and flagella (the organelles for mobility) Some unicellular organisms like Paramecium and Euglena swim in water with the help of cilia and flagella respectively. In multicellular organism some living tissues (epithelial tissues) have cilia. They beat and create a current in the fluid in order to move in a given direction e.g. in the wind pipe (trachea) to push out the mucus and dust particles. Cilia beat like tiny oars or pedals (as in a boat) and flagella bring about whip – like lashing movement. Both are made up of contractile protein tubulin in the form of microtubules. The arrangement of the microtubules in termed 9 + 2, that is, two central microtubules and nine set surrounding them. 8. Centriole It is present in all animal cells (but not in Amoeba), located just outside the nucleus. It is cylindrical, 0.5 µm in length and without a membrane. It has 9 sets of peripheral tubules but none in the centre. Each set has three tubules arranged at definite angles.It has its own DNA and RNA and therefore it is self-duplicating. Function: Centrioles are involved in cell division. They give orientation to the ‘mitotic spindle’ which forms during cell division. 9. Basal bodies These are structures similar to centrioles. They have the same nine sets of triplet organization, as in the centrioles. The cilia and flagella appear to arise from the basal bodies. Centriole 10. Vacuoles Membrane-bound sacs for storage, digestion, and waste removal. Help plants maintain shape. Absence or small in animal cells while common and large in plant cells. Contain the internal cell sap which is a concentrated solution consists of water, sugar, salts, fat, oils, proteins and pigment.  11.Cytoskeleton The cytoskeleton is a complex network of protein filaments that establish a supportive scaffolding system within the cell. Cytoskeletal proteins are located throughout the interior of the cell, anchored to the plasma membrane and traversing the cytoplasm. Organelles reside within the framework established by the cytoskeleton. The cytoskeleton is not simply a passive internal skeleton but is a dynamic regulatory feature of the cell. These components of the cytoskeleton work together as an integrated network of support within the cytoplasm. Actin Actin helps to establish a cytoplasmic protein framework known as microfilaments visualized radiating out from the nucleus to the lipid bilayer of the plasma membrane. Some forms of actin are found only in muscle cells, while other forms of actin are found within the cytoplasm of most cell types. Within the nucleus, actin is involved in the regulation of gene transcription.  Functions of actin in the cytoplasm of non muscle cells include: Regulation of the physical state of the cytosol Cell movement Formation of contractile rings in cell division Regulators of the gel/sol of the cytosol One characteristic of a cell is the physical nature of its cytosol. It can be described either as gel, a more firm state, or sol, a more soluble state. The more structured the actin, the firmer (gel) the cytosol. The less structured (more fragmented) the actin, the more soluble (sol) the cytosol. Actin is continuously tread-milling in both the gel and sol states, contributing to the character of the cytoplasm.  Intermediate filaments They are larger than actin microfilaments and smaller than microtubules. Most intermediate filaments are located in the cytosol between the nuclear envelope and the plasma membrane. They provide structural stability to the cytoplasm, somewhat reminiscent of the way that steel rods can reinforce concrete. There are six categories of intermediate filaments, grouped by their location. Microtubules: Microtubules are the last type of predominant structure observed in the cytoskeleton. The structure of a microtubule resembles a hollow cylindrical tube. They are involved in: 1. Chromosomal movements during nuclear divisions. 2. Formation of cilia and flagella in certain cell types 3. Intracellular transport Molecules of the Cell The cell and its organelles are made of organic chemicals such as proteins, carbohydrates, nucleic acid and fats. These are termed biomolecules. Inorganic molecules such as water and minerals are also present in the cell. A. Water Water with unique physical and chemical properties has made life possible on earth. It is a major constituent of protoplasm. It is a medium in which many metabolic reactions occur. It is universal solvent in which most substances remain dissolved. It is responsible for turgidity of cells. B. Elements necessary for life Elements such as Hydrogen, Carbon, Oxygen, Nitrogen, Calcium, Potassium, Sodium, Magnesium, Phosphorous, Sulphur, Chlorine, Iron, Boron, Silicon, Manganese, Copper, Zinc, Cobalt, Molybdenum and Silicon. Their functions are required for organic compounds of the cell and present as major constitutes. Ca in plant cell wall, C,H,O,N as organic compounds. Act as major cations (Na, K) and anions (Cl) in most physiological process. As cofactor of enzymes participate in most of the biochemical reaction of a cell( Fe, Cu, Mo, Zn, B). Involved in energy transfer reaction (P in ATP). Green pigments chlorophyll in plants have magnesium in the centre.  Carbohydrates Structure Functions Composed of C, H, O Most abundant organic substance present in nature in the form of cellulose in plant cell wall Simple six carbon sugar (glucose) is In both plants and animals, it is used called a monosaccharide as a source of energy Two molecules or units join together An important storage form in plants is to form disaccharide (sucrose) starch and in animals it is glycogen More than ten units of Present in nucleic acids as five carbon monosaccharides join in a chain to sugar ( ribose). form a polysaccharide e,g. starch and cellulose.  Proteins Structure Functions Composed of C, H, O and N Structurally, proteins form integral part of the membranes. Amino acids join together by Functionally in the form of enzymes they peptide bond to form protein play a vital role in metabolic reactions Twenty different amino acids make Synthesis od DNA is regulated by protein numerous simple and complex proteins Based on the complexity of Proteins are so important that nucleic acids structure they can have primary, directly regulate protein synthesis secondary, tertiary and quaternary structures When proteins exist with other molecules they are known as conjugated proteins e.g. glycoprotein, lipoprotein etc Nucleic acids Structure Functions They are two types: Deoxyribose nucleic acid DNA is the main genetic material foe almost (DNA) and Ribose nucleic acid (RNA) organisms except certain viruses They are long chain polymers composed RNA molecules are involved in of units called nucleotides information transfer and protein synthesis Each nucleotide has pentose sugar, nitrogen base and phosphate group DNA has one oxygen less in its sugar molecule Lipids Structure Functions Composed of C, H, O. Amounts of oxygen Due to their low oxygen content, they store is very less and release more energy during oxidation They are synthesized from fatty acids A molecule of fat can yield twice as and glycerol. Simple lipids are called much energy as from carbohydrate glycerides Fats can be saturated or unsaturated Phospholipids are important component of cell membranes Fats are solid at room temperature those that remain liquid at room temperature are called oils Thanks For Your Listening