Medical Biology - Biomolecules PDF

Medical Biology SR. INST. SUAL TATLISULU GIRNE AMERICAN UNIVERSITY – FACULTY OF MEDICINE ❖ e-mail: [email protected] BIOMOLECULES  Outline Carbon: The Framework of Biological Molecules ◦ Hydrocarbon ◦ F...

Medical Biology SR. INST. SUAL TATLISULU GIRNE AMERICAN UNIVERSITY – FACULTY OF MEDICINE ❖ e-mail: [email protected] BIOMOLECULES  Outline Carbon: The Framework of Biological Molecules ◦ Hydrocarbon ◦ Functional groups Proteins: Molecules with Diverse ◦ Isomers ◦ Macromolecules Structures and Functions ◦ Amino acid structure Carbohydrates: Energy Storage and Structural ◦ Peptide bonds Molecules ◦ Primary / Secondary / Tertiary / Quaternary ◦ Monosaccharides ◦ Motifs / Domains ◦ Disaccharides ◦ Polysaccharides Lipids: Hydrophobic Molecules ◦ Phospholipids Nucleic Acids: Information Molecules ◦ Nucleic acid / Nucleotides ◦ DNA / RNA  1. Carbon: The Framework of Biological Molecules Carbon is a chemical element with the symbol C and atomic number 6. It is non-metallic and tetravalent It is atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table.  1. Carbon: The Framework of Biological Molecules The framework of biological molecules consists predominantly of carbon atoms bonded to other carbon atoms (carbon-carbon), or; ◦ Oxygen (O) ◦ Nitrogen (N) ◦ Sulphur (S) ◦ Phosphorus (P) ◦ Hydrogen (H) Carbon atoms can form up to four covalent bonds Molecules containing carbon can form straight chains, branches, or even rings, balls, tubes, and coils.  1. Carbon: The Framework of Biological Molecules Hydrocarbons ◦ Organic molecules consisting only of carbon and hydrogen. ◦ They are by far the dominant components of crude oil, processed petroleum hydrocarbons (gasoline, diesel, kerosene, fuel oil, and lubricating oil), coal tar, creosote, dyestuff, and pyrolysis waste products. ◦ carbon–hydrogen covalent bonds store considerable energy, hydrocarbons make good fuels ◦ Many hydrocarbons occur in nature. In addition to making up fossil fuels, they are present in trees and plants, Types of hydrocarbons; ◦ Alkanes - have only single bonds ◦ Alkenes - contain a carbon-carbon double bond ◦ Alkynes - contain a carbon-carbon triple bond ◦ Aromatic Compounds  1. Carbon: The Framework of Biological Molecules Carbon and hydrogen atoms both have very similar electro-negativities. Electrons in C—C and C—H bonds are therefore evenly distributed, with no significant differences in charge over the molecular surface. So; hydrocarbons are nonpolar. However, functional groups can be polar, for ex/ hydroxyl and carbonyl (C==O) groups are polar ◦ Because of the electronegativity of the oxygen atoms. Functional Groups ◦ An atom/group of atoms joined in a specific manner which is responsible for the characteristics chemical properties of the organic compounds. ◦ Common functional groups; ◦ Hydroxyl (OH) ◦ Acidic Carboxyl (COOH) ◦ Phosphate (PO4) ◦ Basic amino (NH2) Fig. The primary functional chemical groups. These groups tend to act as units during chemical reactions and give specific chemical properties to the molecules that possess them. Amino groups, for example, make a molecule more basic, and carboxyl groups make a molecule more acidic.  1. Carbon: The Framework of Biological Molecules Isomers Isomers have the same molecular formulas but different structure If there are differences in the actual structure of their carbon skeleton, we call them structural isomers. Another form of isomers, called stereoisomers, have the same carbon skeleton but differ in how the groups attached to this skeleton are arranged in space Enzymes in biological systems usually recognize only a single, specific stereoisomer. A subcategory of stereoisomers, called enantiomers.  1. Carbon: The Framework of Biological Molecules Enantiomers ◦ Are actually mirror images of each other. A molecule that has mirror-image versions is called a chiral molecule. ◦ Chiral compounds are characterized by their effect on polarized light. Polarized light has a single plane, and chiral molecules rotate this plane either to the right (dextro) or left (levo) ◦ We therefore call the two chiral forms D for dextrorotatory and L for laevorotatory.  1. Carbon: The Framework of Biological Molecules Macromolecules A macromolecule is a very large molecule important to biophysical processes, simply, a very large molecule that contains thousands of atoms or more. Biological macromolecules (Biomolecules) are grouped into; ◦ Carbohydrates ◦ Nucleic acids ◦ Proteins ◦ Lipids  1. Carbon: The Framework of Biological Molecules In many cases, these macromolecules are polymers. ◦ Polymer is a long molecule built by linking together a large number of small composed of many repeating units called monomers. ◦ Monomer is a molecule that can react together with other monomer molecules to form a larger polymer chain The nature of a polymer is determined by the monomers used to build the polymer. Example of polymers; ◦ Complex carbohydrates such as starch are polymers composed of simple ring-shaped sugars. ◦ Nucleic acids (DNA and RNA) are polymers of nucleotides ◦ Proteins are polymers of amino acids, and lipids are polymers of fatty acids Carbohydrates, nucleic acids, and proteins all form polymers and are shown with the monomers used to make them.  1. Carbon: The Framework of Biological Molecules These long chains are built via chemical reactions termed dehydration reactions and are broken down by hydrolysis reactions. Dehydration Reactions ◦ Despite the differences between monomers of these major polymers, the basic chemistry of their synthesis is similar. To form a covalent bond between two monomers, an —OH group is removed from one monomer, and a hydrogen atom (H) is removed from the other. (Loose of water molecule) ◦ For every subunit added to a macromolecule, one water molecule is removed. Example; For example, this simple chemistry is the same for linking amino acids together to make a protein or assembling glucose units together to make starch. This reaction is also used to link fatty acids to glycerol in lipids.  1. Carbon: The Framework of Biological Molecules Hydrolysis Reactions ◦ A hydrolysis reaction is a reaction in which one molecule breaks apart to form multiple smaller molecules. ◦ In this process, a hydrogen atom is attached to one subunit and a hydroxyl group to the other, breaking a specific covalent bond in the macromolecule ◦ Cells disassemble macromolecules into their a. Biological macromolecules are polymers formed by linking monomers constituent subunits through reactions that are the together through dehydration reactions. This process releases a water reverse of dehydration—a molecule of water is added molecule for every bond formed. b. Breaking the bond between subunits involves hydrolysis, which reverses the loss of a water molecule by instead of removed dehydration. Carbonhydrates  2. Carbohydrates: Energy Storage and Structural Molecules oThey are the most abundant biomolecules on earth. oCarbohydrates constitute the third largest group of organic molecules found in living things, after nucleic acids and proteins. oThe breakdown of CHs is the main metabolic pathway that produces energy in most non-photosynthetic cells o Because they contain many carbon– hydrogen (C—H) bonds, which release energy when oxidation occurs, carbohydrates are well suited for energy storage. o.Carbohydrates consist of carbon (C), hydrogen (H) and oxygen (O) atoms; most of them have the closed formula (CH2O)n. Some of them contain nitrogen, sulfur, phosphorus.  2. Carbohydrates: Energy Storage and Structural Molecules o There are three separate classifications regarding carbohydrates. o The number of carbon atoms in their structure o The number of simple sugars in their structure o The aldehyde and ketone groups found in their structure  2. Carbohydrates: Energy Storage and Structural Molecules CHs are among the most important energy-storage molecules, and they exist in several different forms. The number of simple sugars in their structure: ◦ Monosaccharides - also called simple sugars, are the simplest forms of sugar and the most basic units from which all carbohydrates are built. The most abundant monosaccharide in nature: D-glucose (dextrose) ◦ Oligosaccharides - short chain structure consisting of two or more monosaccharides are called oligosaccharides. Monosaccharides are linked by glycosidic bonds. Structures formed by 2 monosaccharides are called disaccharides. ◦ In general, all monosaccharides and disaccharides are names ending with the suffix -ose. Ex: Sucrose is a disaccharide formed by the combination of a glucose and a fructose molecule. ◦ Polysaccharides - Sugar polymers containing 20 or more monosaccharide units. Ex: cellulose (linear chain), glycogen (branched chain). Are the most abundant carbohydrates found in food.  2. Carbohydrates: Energy Storage and Structural Molecules Monosaccharides ◦ The simplest carbohydrates ◦ They are colorless and water soluble ◦ They are commonly in a circular structure ◦ Contains 1 or more hydroxyl groups ◦ According to reagent groups; They are aldehydes or ketones. (according to the location of the carbonyl group) ◦ According to the length of the carbon chain; Diose Triose Tetrose There is only one possible diose, glycolaldehyde (2-hydroxyethanal), Pentose Hexose Heptose which is an aldodiose (a ketodiose is not possible since there are only two carbons).  2. Carbohydrates: Energy Storage and Structural Molecules Monosaccharides ◦ Simple sugars that play the central role in energy storage have six carbon atoms ◦ Six-carbon sugars can exist in a straight-chain form, but dissolved in water (an aqueous environment) they almost always form rings. ◦ Monosaccharides, or simple sugars are often used as building blocks to form larger molecules. The five-carbon sugars ribose and deoxyribose are components of nucleic acids. 2. Carbohydrates: Energy Storage and Structural Molecules ◦ Monosaccharides bind with purine (adenine, guanine), pyrimidine (thymine, cytosine and uracil) and phosphates to form nucleic acids (DNA, RNA). ◦ binds to proteins and forms glycoproteins ◦ glycolipids by binding to lipids ◦ And by binding to other compounds, they form carbohydrate derivatives such as glycosides, sugar acids and phosphate esters. ◦ Monosaccharides that are important as a nutritional source are hexoses. The most important of these are glucose (blood and grape sugar), fructose (fruit sugar, levulose) and galactose (milk sugar). *Blood glucose levels are measured in the diagnosis of diabetes. 2. Carbohydrates: Energy Storage and Structural Molecules The most important of the six-carbon monosaccharides for energy storage is glucose. ◦ Ex/ Glucose has seven energy-storing C—H bonds, depending on the orientation of the carbonyl group (C= O) when the ring is closed, glucose can exist in two different forms: alpha (α) or beta (β).  2. Carbohydrates: Energy Storage and Structural Molecules Disaccharides ◦ serve as transport molecules in plants and provide nutrition in animals ◦ Transport forms of sugars are commonly made by linking two monosaccharides together to form a disaccharide. ◦ Monosaccharides are linked to each other by glycosidic bonds to form glycosides. ◦ Maltose consists of two glucoses: It is rarely found in nature. It is obtained from starch by acid hydrolysis or -amylase enzyme hydrolysis. ◦ Lactose consists of glucose and galactose: It is hydrolyzed by acid or the lactase enzyme. ◦ Sucrose consists of glucose and fructose: They are formed as a result of photosynthesis of plants. They are stored in some plants (sugar beets, sugar cane). How disaccharides form Some disaccharides are used to transport glucose from one part of an organism’s body to another; one example is sucrose (a), which is found in sugarcane. Other disaccharides, such as maltose (b), are used in grain for storage. Lactose (glucose+galactose) Maltose (glucose+glucose) Sucrose (glucose+fructose)  2. Carbohydrates: Energy Storage and Structural Molecules Polysaccharides ◦ Provide energy storage and structural components ◦ Longer polymers (more than 20 monosaccharides) made up of monosaccharides that have been joined through dehydration reactions ◦ Example; ◦ Starch - a storage polysaccharide, consists entirely of α-glucose molecules linked in long chains. ◦ Glycogen - is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. ◦ Cellulose - a structural polysaccharide, also consists of glucose molecules linked in chains, but these molecules are β-glucose.  2. Carbohydrates: Energy Storage and Structural Molecules Polysaccharides o Polysaccharides consisting entirely of the same monosaccharide are called homopolysaccharides (Starch, cellulose). o Starch and glycogen consist of monosaccharides used closely together and serve as storage. o Those consisting of different monosaccharides are called heteropolysaccharides (pectin). ◦ Peptidoglycan; tough layer of bacterial cell wall n(Monosaccharides) ===} Polisaccharides + (n-1)water 2. Carbohydrates: Energy Storage and Structural Molecules Polysaccharides Most show branched structure. Some of them show helix structures. They are insoluble and they are also resistant to enzymatic degradation. As the regularity in the structures of polysaccharide molecules decreases, their solubility increases. In aqueous systems, polysaccharides can absorb water, swell, and partially or completely dissolve. It is used as a thickener, gelling agent, flow, deformation properties and texture regulator in foods. When heated, water-soluble unbranched polysaccharides precipitate or gel. A gel is a continuous, three-dimensional network structure consisting of interconnected molecules or particles and holds a large volume of liquid phase. Gels have the properties of both solids and liquids  2. Carbohydrates: Energy Storage and Structural Molecules Energy storage Plants use starch - There are two types of glucose monomers in its structure. Amylose Amylopectin Animals use glycogen - is the main storage polysaccharide of animal cells. (It is abundant in liver) Dextran, bacterial and yeast polysaccharides  2. Carbohydrates: Energy Storage and Structural Molecules Structural support Homopolysaccharides: Plants use cellulose Arthropods and fungi use chitin (the structural material found in arthropods and many fungi, is a polymer of N-acetylglucosamine, a substituted version of glucose. When cross-linked by proteins, it forms a tough, resistant surface material that serves as the hard exoskeleton of insects and crustaceans) Heteropolysaccharides: Peptidoglycan: Structure of the bacterial cell wall: N-acetylglucosamine and N-acetylmuramic acid Agar: Consists of D-galactose and L-galactose derivatives. (agar is also a bacterial medium) Hyaluronan (hyaluronic acid): is a glycosaminoglycan: D-glucuronic acid + N- acetylglucosamine. In vertebrates, it provides flexibility in the extracellular matrix of the skin and connective tissue, and viscosity in the joints. 2. Carbohydrates: Energy Storage and Structural Molecules Cellulose ◦ Although some chains of sugars store energy, others serve as structural material for cells. ◦ The properties of a chain of glucose molecules consisting of all β-glucose are very different from those of starch. These long, unbranched β-linked chains make tough fibers. Cellulose is the chief component of plant cell walls Chitin ◦ the structural material found in arthropods and many fungi, is a polymer of N-acetylglucosamine, a substituted version of glucose. When cross-linked by proteins, it forms a tough, resistant surface material that serves as the hard exoskeleton of insects and crustaceans Polysaccharides and oligosaccharides, in addition to important roles such as energy storage (starch, glycogen, dextran) and structural materials (cellulose, chitin, peptidoglycan), also serve as information carriers. - communication between the cell and extracellular environments - transport and protein labelling Ex: glycocalyx Oligosaccharides in the glycocalyx structure surrounding the cell play a role in many important cellular activities such as cell-cell recognition, cell adhesion and migration, blood clotting, immune response, and wound healing. In most of these cases, the information-carrying carbohydrate is covalently linked to a protein or lipid molecule to form the glycoconjugate, the biologically active molecule. In this sense, three types of biologically active glycoconjugates can be mentioned: proteoglycans, glycoproteins and glycolipids.  2. Carbohydrates: Energy Storage and Structural Molecules Glycocalyx The glycocalyx, also known as the pericellular matrix and sometime cell coat It is the second covering that covers the plasma membrane from the outside. The cell membrane, located on the outer surface of the cell, consists of carbohydrates. Glycocalyx extends from the membrane of endothelial cells to the vascular lumen, prevents leukocytes and platelets from contacting with endothelial cells, and plays a key role in maintaining the stability of the internal environment It consists of glycolipid and glycoprotein units formed as a result of the binding of oligosaccharides to lipids or proteins. (glycoconjugate) The glycocalyx has four important functions in the cell: 1) It allows cells to recognize each other. 2) Contact causes inhibition. 3) It provides antigenic properties to the cell. 4) It acts as a receptor. 2. Carbohydrates: Energy Storage and Structural Molecules Glycoprotein: a protein that has one or more complex oligosaccharides covalently linked. They are found in blood, in the extracellular matrix, as part of the glycocalyx. They are found in Golgi complexes and inside organelles such as lysosomes. It is rich in information due to its high binding affinity through carbohydrate-binding proteins called lectins and the formation of highly specific recognition sites. Glycolipid: membrane sphingolipids with hydrophilic head groups of oligosaccharides. As with glycoproteins, they act as specific recognition sites for lectins.  2. Carbohydrates: Energy Storage and Structural Molecules Proteoglycans On the cell surface and extracellular matrix, glycosaminoglycans form very large aggregates by covalently bonding with proteins. These structures are called proteoglycans (mucoproteins). Proteoglycans are mostly composed of polysaccharides (95% or more). Proteoglycans are the basic component of all extracellular matrices. Most proteoglycans are secreted into the extracellular matrix, although some function as integral membrane proteins.  3. Nucleic Acids: Information Molecules Nucleic acids carry information inside cells ◦ Ex/ Just as disks contain the information in a computer Two main varieties of nucleic acids ◦ Deoxyribonucleic acid (DNA) ◦ Ribonucleic acid (RNA). https://www.khanacademy.org/science/ap-biology/gene-expression-and-regulation/dna-and-rna-structure/v/introduction-to-nucleic-acids-and-nucleotides  Base pairing; Adenine (A) with Thymine (T) 3. Nucleic Acids: Information Molecules Cytosine (C) with Guanine (G) Deoxyribonucleic acid (DNA) ◦ is the molecule that carries genetic information for the development and functioning of an organism ◦ DNA encodes the genetic information needed for protein synthesis ◦ DNA, found primarily in the nuclear region of cells. (eukaryotic) ◦ DNA is made of two linked strands that wind around each a shape known as a double helix  3. Nucleic Acids: Information Molecules Ribonucleic Acid (RNA) ◦ is a nucleic acid present in all living cells that has structural similarities to DNA ◦ Unlike DNA, however, RNA is most often single-stranded ◦ Contains ribose instead of deoxyribose ◦ RNA uses information in DNA to specify sequence of amino acids in proteins ◦ Different types of RNA exist in cells: messenger RNA (mRNA), ribosomal RNA (rRNA) and transfer RNA (tRNA). Base pairing; Adenine (A) with Uracil (U) Cytosine (C) with Guanine (G)  3. Nucleic Acids: Information Molecules Types of RNA; ◦ Messenger RNA (mRNA) copies portions of genetic code, a process called transcription, and transports these copies to ribosomes, which are the cellular factories that facilitate the production of proteins from this code. ◦ Transfer RNA (tRNA) is responsible for bringing amino acids, basic protein building blocks, to these protein factories, in response to the coded instructions introduced by the mRNA. This protein-building process is called translation. ◦ Ribosomal RNA (rRNA) is a component of the ribosome factory itself without which protein production would not occur. DNA versus RNA. DNA forms a double helix, uses deoxyribose as the sugar in its sugar–phosphate backbone, and uses thymine among its nitrogenous bases. RNA is usually single- stranded, uses ribose as the sugar in its sugar– phosphate backbone, and uses uracil in place of thymine.  DNA RNA Function DNA replicates and stores genetic information. It is a blueprint for all genetic RNA converts the genetic information contained within DNA to a format used to build information contained within an organism. proteins, and then moves it to ribosomal protein factories. DNA consists of two strands, arranged in a double helix. These strands are made RNA only has one strand, but like DNA, is made up of nucleotides. RNA strands are Structure up of subunits called nucleotides. Each nucleotide contains a phosphate, a 5- shorter than DNA strands. RNA sometimes forms a secondary double helix structure, but carbon sugar molecule and a nitrogenous base. only intermittently. DNA is a much longer polymer than RNA. A chromosome, for example, is a single, Length RNA molecules are variable in length, but much shorter than long DNA polymers. A large long DNA molecule, which would be several centimetres in length when unravelled. RNA molecule might only be a few thousand base pairs long. The sugar in DNA is deoxyribose, which contains one less hydroxyl group than RNA contains ribose sugar molecules, without the hydroxyl modifications of deoxyribose. Sugar RNA’s ribose. The bases in DNA are Adenine (‘A’), Thymine (‘T’), Guanine (‘G’) and Cytosine RNA shares Adenine (‘A’), Guanine (‘G’) and Cytosine (‘C’) with DNA, but contains Uracil Bases (‘C’). (‘U’) rather than Thymine. Base Pairs Adenine and Thymine pair (A-T) Adenine and Uracil pair (A-U) Cytosine and Guanine pair (C-G) Cytosine and Guanine pair (C-G) RNA forms in the nucleolus, and then moves to specialised regions of the cytoplasm DNA is found in the nucleus, with a small amount of DNA also present in Location depending on the type of RNA formed. mitochondria. Due to its deoxyribose sugar, which contains one less oxygen-containing hydroxyl RNA, containing a ribose sugar, is more reactive than DNA and is not stable in alkaline Reactivity group, DNA is a more stable molecule than RNA, which is useful for a molecule conditions. RNA’s larger helical grooves mean it is more easily subject to attack by which has the task of keeping genetic information safe. enzymes. Ultraviolet (UV) DNA is vulnerable to damage by ultraviolet light. RNA is more resistant to damage from UV light than DNA. Sensitivity  3. Nucleic Acids: Information Molecules Nucleic acids are nucleotide polymers ◦ Nucleic acids are long polymers of repeating subunits called nucleotides. ◦ Polymer- Nucleic acids ◦ Monomer – Nucleotides ◦ Each nucleotide consists of three components; ◦ a pentose, or five-carbon sugar (ribose in RNA and deoxyribose in DNA) ◦ a phosphate (—PO4) group ◦ organic nitrogenous (nitrogen-containing) base  3. Nucleic Acids: Information Molecules Nucleic Acid ◦ simply a chain of five- carbon sugars linked together by phosphodiester bonds with a nitrogenous base protruding from each sugar Two types of nitrogenous bases occur in nucleotides. ◦ Purines, are large, double-ring molecules found in both DNA and RNA; the two types of purines are adenine (A) and guanine (G). ◦ Pyrimidines, are smaller, single-ring molecules; they include cytosine (C, in both DNA and RNA), thymine (T, in DNA only), and uracil (U, in RNA only).  Adenine pairs with thymine with 2 hydrogen bonds. Guanine pairs with cytosine with 3 hydrogen bonds.  Nucleotide is any member of the class of organic compounds in which the molecular structure comprises a nitrogen-containing unit (base) linked to a sugar and a phosphate group. They are monomeric units of nucleic acids and also serve as sources of chemical energy (ATP, GTP), participate in cellular signalling (cAMP, cGMP) and function as important cofactors of enzymatic reactions (coA, FAD, FMN, NAD+). The molecule without the phosphate group of nucleotides is called as nucleoside. Nucleosides are glycosylamines consisting simply of a nitrogenous base and a five-carbon sugar (either ribose or deoxyribose).  3. Nucleic Acids: Information Molecules Other nucleotides are vital components of energy reactions ◦ Adenine is a key component of the molecule Adenosine Triphosphate (ATP), the energy currency of the cell. ◦ ATP is used to drive energetically unfavourable chemical reactions, to power transport across membranes, and to power the movement of cells. ◦ Nicotinamide Adenine Dinucleotide (NAD+) and Flavin Adenine Dinucleotide (FAD) ◦ These molecules function as electron carriers in a variety of cellular processes  4. Proteins: Molecules with Diverse Structures and Functions A protein molecule is very large compared with molecules of sugar or salt and consists of many amino acids joined together to form long chains. Summary of the functions; I. Enzyme catalysis II. Defence III. Transport IV. Support V. Motion VI. Regulation VII. Storage  4. Proteins: Molecules with Diverse Structures and Functions o Enzyme catalysis - Enzyme catalysis is the increase in the rate of a process by a biological molecule, an "enzyme”. ◦ Enzymes are defined as biocatalyst substances that allow biochemical reactions to occur rapidly under normal conditions and constitute the basic characteristics of living tissue. ex: Amylase, pepsin, lipase are examples of important catalytic proteins or enzymes. o Defence – Other globular proteins use their shapes to “recognize” foreign microbes and cancer cells. They are proteins that defend organisms against invasion by other species, protecting the organism from damage. Immunoglobulins are specialized proteins made by vertebrate lymphocytes. Immunoglobulins can recognize and precipitate or neutralize ◦ Bacteria, ◦ Viruses or ◦ Foreign proteins (antigens) of another species that invade the organism.  4. Proteins: Molecules with Diverse Structures and Functions oTransport - They are proteins that bind specific molecules or ions and transport them from one organ to another or from one side of the cell membrane to the other. Serum albumin is the best-known carrier protein; Bilirubin, calcium, fatty acids and many drugs are transported by binding to serum albumin. Hemoglobin carries oxygen, Lipoproteins, lipid-carrying, Transferrin is an example of an important carrier protein that transports iron. Carrier proteins found in the plasma membranes and intracellular membranes of all organisms bind glucose, amino acids and other substances; They transport them from one side of the membrane to the other. o Support - Protein fibers play structural roles. These fibers include keratin in hair, fibrin in blood clots, and collagen. ◦ The main structure of tendons and cartilage consists of collagen, which has very high tensile strength. ◦ Ligaments contain elastin, a structural protein capable of stretching in two dimensions. ◦ Hair, nails and feathers contain keratin. ◦ The main component of silk fibers and spider webs is fibroin. The wing axes of some insects are made of resilinin.  4. Proteins: Molecules with Diverse Structures and Functions o Motion - They are proteins that can contract or move spontaneously. Skeletal muscles contract through the sliding motion of two kinds of protein filaments: actin and myosin. Tubulin is the protein that forms microtubules. Microtubules in the cells move together with the dynein protein in the flagella and cilia to move the cells. o Regulation - They are proteins that assist in cellular regulation or physiological activity. Proteins also play regulatory roles withing the cell such as turning on and shutting off the genes during development. Some hormones, such as insulin and growth hormone, are regulatory proteins. Insulin is effective in regulating sugar metabolism. Growth hormone is effective in regulating growth. Some regulatory proteins wrap DNA; They regulate the biosynthesis of enzymes and RNA molecules.  4. Proteins: Molecules with Diverse Structures and Functions oStorage - They are proteins that serve as biological reserves for metal ions and amino acids used by the organism. The main protein of egg white, ovalbumin, and the main protein of milk, casein, are nutritional proteins; They are amino acid stores. Many plant seeds also store the nutritional proteins necessary for the growth of the germinating seed. The best-known storage protein in wheat is gluten. Ferritin is an iron-storing protein.  4. Proteins: Molecules with Diverse Structures and Functions Proteins are polymers of amino acids ◦ Proteins are linear polymers made with 20 different amino acids ◦ Composed of 1 or more long, unbranched chains ◦ Each chain is a polypeptide ◦ Amino acids, contain an amino group (—NH2) and an acidic carboxyl group (—COOH) ◦ The specific order of amino acids determines the protein’s structure and function ◦ Amino acids are briefly represented by a single letter or three letters. For example, Glycine; Gly or G  4. Proteins: Molecules with Diverse Structures and Functions Amino acid structure Compounds with an amino (-NH2) and carboxyl group ◦ Amino acids are monomers (-COOH) attached to the same carbon atom (α) are called ◦ Amino acid structure; amino acids ◦ Central carbon atom ◦ Amino group ◦ Carboxyl group ◦ Single hydrogen ◦ Variable R group R groups allow them to differ from each other; Structure, dimension, electric charges and affects its solubility in water Classification of Amino Acids Based on the properties of R groups, amino acids can be grouped into 5 main classes. Polarity: non-polar (hydrophobic), polar (hydrophilic) Nonpolar, Aliphatic R Groups Aromatic R Groups Polar, Uncharged R Groups Positively Charged (basic) R Groups Negative Charge (Acidic) R Groups Other Amino Acids In addition to the commonly produced 20 aa, proteins may contain residues produced by modifications of amino acids already incorporated into a polypeptide. ◦ 4-hydroxyproline – proline derivative (found in plant cell wall proteins and in the collagen structure, the fibrous protein of connective tissue. ◦ 5-hydroxylysine – lysine derivative (found in collagen structure) ◦ ɣ-carboxyglutamate – glutamate derivative (formed as a result of the modification of glutamate by a reaction stimulated by vitamin K. This modification enables the protein to bind calcium. This event is one of the most basic events in blood clotting. ◦ Desmosin – consists of 4 Lysine residues – participates in the elastin structure ◦ Selenocysteine – contains selenium instead of sulfur in cysteine Note: There is no triple code for these. Note: Nearly 300 AAs were found in cells, but not all of them participate in the protein structure. Essential Amino Acids Amino acids that cannot be synthesized by the organism and must be taken from outside with food are called essential amino acids or exogenous amino acids. Beans contain more protein than meat, but they are not as valuable as meat. WHY? Because; It does not contain as many essential amino acids as necessary. ◦ If there is an essential amino acid deficiency, the remaining 19 amino acids cannot be used for protein synthesis. However, they are catabolized and negative nitrogen balance occurs. ◦ Essential amino acids vary among animals. Amino acids that are essential for some species may not be essential for others. ◦ It also varies depending on age. Branched-chain amino acids (BCAAs) are essential nutrients including leucine, isoleucine, and valine. ◦ Each carries an aliphatic side chain containing a methyl group (as a substituent). ◦ They should be taken from the diet in high-bodied animals. In other words, they are essential.  4. Proteins: Molecules with Diverse Structures and Functions Peptide bonds ◦ The amino and carboxyl groups on a pair of amino acids can undergo a dehydration reaction to form a covalent bond. ◦ The covalent bond that links two amino acids is called a peptide bond ◦ So, amino acids are joined by peptide bonds. When several amino acids are combined in this way, it is called an oligopeptide, and when many amino acids are combined in this way, it is called a polypeptide. Because the -SH group of cysteine allows it to dimerize via the disulfide (-S-S-) bond, this amino acid is often found in its oxidized form in proteins. This oxidized form is cysteine. 2 cysteine molecules are joined by a disulfide bond. Disulfide bonded molecules are strongly hydrophobic and increase the stability of the protein structure. Cystine covalently binds different regions of polypeptide chains. Thus, it stabilizes proteins and makes them more resistant to denaturation.  4. Proteins: Molecules with Diverse Structures and Functions Four levels of protein structure ◦ The shape of a protein determines its function ◦ Primary structure: Amino acid sequence ◦ Secondary structure: Interaction of groups in the peptide backbone ◦ Tertiary structure – Final folded shape of a globular protein ◦ Quaternary structure: Subunit arrangements https://www.youtube.com/watch?v=hok2hyED9go  4. Proteins: Molecules with Diverse Structures and Functions 1. Primary Structure ◦ Defined as the linear amino acid sequence of a protein's polypeptide chain ◦ The primary structure of a protein is its amino acid sequence  4. Proteins: Molecules with Diverse Structures and Functions 2. Secondary Structure ◦ interaction of groups in the peptide backbone ◦ Secondary structure results from hydrogen bonds forming between nearby amino acids. ◦ Two types; ◦ 𝞪 helix - peptide groups that interact with one another coiled into a spiral form ◦ 𝞫 sheet - peptide aligned next to each other to form a planar structure  4. Proteins: Molecules with Diverse Structures and Functions 3. Tertiary Structure ◦ The final folded shape of a globular protein is called its tertiary structure ◦ Refers to the three‐dimensional arrangement of all the atoms that constitute a protein molecule ◦ A protein is initially driven into its tertiary structure by hydrophobic exclusion from water  4. Proteins: Molecules with Diverse Structures and Functions 4. Quaternary Structure ◦ two or more polypeptide chains associate to form a functional protein ◦ The arrangement of these subunits is termed its quaternary structure Levels of protein structure. The primary structure of a protein is its amino acid sequence. Secondary structure results from hydrogen bonds forming between nearby amino acids. This produces two different kinds of structures: beta (β)-pleated sheets, and coils called alpha (α)-helices. The tertiary structure is the final 3-D shape of the protein. Quaternary structure is only found in proteins with multiple polypeptides.  4. Proteins: Molecules with Diverse Structures and Functions Additional structural characteristics ◦ Motifs and Domains Motifs ◦ Common elements of secondary structure seen in many polypeptides ◦ Useful in determining the function of unknown proteins Domains ◦ Functional units within a larger structure ◦ Most proteins made of multiple domains that perform different parts of the protein’s function ◦ functional domains of proteins may also help the protein to fold into its proper shape Motifs and domains. The elements of secondary structure can combine, fold, or crease to form motifs. These motifs are found in different proteins and can be used to predict function. Proteins also are made of larger domains, which are functionally distinct parts of a protein. The arrangement of these domains in space is the tertiary structure of a protein.  4. Proteins: Molecules with Diverse Structures and Functions Chaperones ◦ Chaperone proteins help protein fold correctly ◦ They protect proteins when they are in the process of folding, shielding them from other proteins that might bind and hinder the process ◦ Many are heat shock proteins, produced in greatly increased amounts when cells are exposed to elevated temperature ◦ High temperatures cause proteins to unfold, and heat shock chaperone proteins help the cell’s proteins to refold properly.  4. Proteins: Molecules with Diverse Structures and Functions ◦ Deficiencies in chaperone proteins (protein misfolding) implicated in certain diseases ◦ Cystic fibrosis - hereditary disorder in which a mutation disables a vital protein that moves ions across cell membranes. ◦ In some individuals, protein appears to have correct amino acid sequence but fails to fold  4. Proteins: Molecules with Diverse Structures and Functions Protein Denaturation ◦ Protein loses structure and function ◦ So they are inactivated ◦ Due to environmental conditions ◦ pH ◦ Temperature ◦ Ionic concentration of solution ◦ UV  5. Lipids: Hydrophobic Molecules Lipids ◦ Loosely defined group of molecules with one main chemical characteristic ◦ They are insoluble in water ◦ They form a group of organic compounds. ◦ They are composed of C, H and O, but there is no fixed relationship between the amounts of these elements. ◦ High proportion of nonpolar C—H bonds causes the molecule to be hydrophobic ◦ Fats and fat-like substances are referred to as lipids. ◦ Example of lipids; ◦ Fats ◦ Oils ◦ Waxes ◦ even some Vitamins ◦ The functions of lipids differ, as do their chemical structures. ◦ Fats and oils are the primary storage form of energy in many organisms.  5. Lipids: Hydrophobic Molecules Fats ◦ Fats consist of complex polymers of fatty acids attached to glycerol ◦ A fat molecule commonly called “Triglycerides” which is composed of ◦ 1 glycerol and 3 fatty acids ◦ Fats are excellent energy storage molecules Fatty acids ◦ Chain length varies ◦ Saturated – no double bonds between carbon atoms ◦ Higher melting point, animal origin ◦ Unsaturated – 1 or more double bonds ◦ Low melting point, plant origin ◦ Trans fats produced industrially Functions of Lipids 1. Storage Lipids Fats and oils, which are universally used as a form of energy storage in almost all living organisms, are derivatives of fatty acids. Fatty acids are hydrocarbon derivatives. In their structure, there is a carboxyl group at the end of the 4-36 carbon hydrocarbon chain. Fatty Acids o Fatty acids release H+ ions to the environment. That's why they show acid character. o Therefore, the carboxyl group determines the acidic character of the fatty acid molecule. Saturated Fatty Acids o Saturated (alkane) fatty acids are fatty acids consisting of a single covalent bond with carbon- carbon (-C-C-) bonds. o In other words, they are characterized by not containing any double bonds. o Natural oils and fatty acids generally contain an even number of carbon atoms (C4-C26). o General closed formulas are Cn H2n O2 or CH3(CH2) nCOOH oFreezing, Melting and Boiling points increase as the number of carbon increases.  Unsaturated Fatty Acids o Unsaturated fatty acids are characterized by one or more double bonds (-C=C-) in their chain structure. o They are divided into groups as follows according to the number of double bonds; o Monoene unsaturated acids: A double bond fatty acid molecule (oleic acid C18:1) o Diene unsaturated acids: Fatty acid molecules with two double bonds(linoleic acid C18:2) o Triene unsaturated acids: Three double-bonded fatty acid molecules(linolenic acid C18:3) o Polyene unsaturated acids: More than three double bond fatty acid molecules (arachidonic C20:4) Common saturated and unsaturated fatty acids Nomenclature of Fatty Acid- IUPAC delta Or 18:1(9) Nomenclature of Fatty Acid- ω (omega) o Polyunsaturated fatty acids (PUFAs) contain polyunsaturated fatty acids, which contain a double bond between the third and fourth carbons after the methyl group at the end of the chain; o They are very important for our composition. o The physiological role of PUFAs is closely related to the location of the first double bond closest to the methyl end of the chain. oThe carbon of the methyl group, that is, the methyl carbon that is furthest from the carboxyl group, is called the -omega carbon and is given the number 1. Essential fatty acids; Humans cannot synthesize omega-3 PUFA alpha-linolenic acid (ALA) enzymatically and need to obtain it from outside through diet. It can synthesize important 2 omega-3 PUFAs from ALA through intracellular enzymatic activities; EPA and DHA. Deficiency of omega-3 and omega-6 PUFAs in the diet increases the risk of cardiovascular disease. Fatty Acids - Unsaturated Fatty Acids Since essential fatty acids cannot be synthesized in the human organism, they must be taken daily with food. Deficiencies cause functional disorders. For example, skin disorders, weakening of memory-mental functions, decrease in visual function, eczema, poor blood circulation, growth retardation in children, etc. can be seen. Triacylglycerol (=triglyceride, fats, neutral fats) They are the simplest lipids composed of fatty acids. It consists of 3 fatty acids, each of which forms an ester bond with the glycerol molecule. Triacylglycerols provide stored energy and insulation It is found in the cytosol of most eukaryotic cells in the form of microscopic oil droplets and serves as metabolic fuel depots. In vertebrates, special cells called adipocytes or fat cells store large amounts of triacylglycerol, filling almost the entire cell. Triacylglycerols, used as stored energy, have two important advantages over glycogen and starch. 1. the carbon atoms of fatty acids are reduced more than the carbon atoms of sugars. Therefore, the energy yield from the oxidation of triacylglycerols is twice as high as the energy yield from the oxidation of CHs. 2. they are hydrophobic so they are not hydrated. The organism that carries only fat as fuel does not have to carry the additional weight of water molecules retained in the structure as a result of the hydration of the stored polysaccharides. Humans have fatty tissue in the subcutaneous, abdominal cavity and mammary glands. Obese people store up to 15-20 kg of triacylglycerol in their adipocytes. It is known that dietary trans fatty acids cause cardiovascular diseases. ◦ Increased triacylglycerols and LDL cholesterol levels in the blood ◦ Causes HDL levels to decrease 2- Structural Lipids in the Membrane It has a double-layer lipid structure. Membrane lipids are amphipathic: one end of the molecule is hydrophilic and the other end is hydrophobic. (polar head and non-polar tails) If the polar head group + hydrophobic part is added via phosphodiester bond: phospholipid Glycolipid if it does not contain phosphate but has a simple sugar or complex oligosaccharide polar end Phospholipids ◦ Complex lipid molecules called phospholipids ◦ Most important molecules of the cell because they form the core of all biological membranes The basic structure of a phospholipid includes three kinds of subunits: ◦ Glycerol – three carbon alcohol, forms the backbone of the phospholipid molecular ◦ Fatty acids - long chains of (hydrocarbon chains) ending in a carboxyl (—COOH) group. Two fatty acid attached to the glycerol. ◦ A phosphate group – Attached to one end of the glycerol. 5. Lipids: Hydrophobic Molecules Lipids spontaneously form micelles or lipid bilayers in water. In an aqueous environment, lipid molecules orient so that their polar (hydrophilic) heads are in the polar medium, water, and their nonpolar (hydrophobic) tails are held away from the water. (a) Droplets called micelles can form, or (b) phospholipid molecules can arrange themselves into two layers; in both structures, the hydrophilic heads extend outward and the hydrophobic tails inward. This second example is called a phospholipid bilayer. Common derivatives of lipids Sphingolipids One polar head, 2 non-polar tails Unlike glycerophospholipids and galactolipids, they do not contain glycerol. ◦ 1 molecule of sphingosine or its derivative ◦ 1 molecule of fatty acid ◦ 1 polar head In some cases, a glycosidic bond may be added to the structure, and in other cases, a phosphodiester bond may be added to the structure. Ex: Glycosphingolipids as determinants of blood groups: Human blood groups (O, A, B) are determined by the oligosaccharide head groups of glycosphingolipids. Sterols They have 4 fused rings and 1 hydroxyl group. The most important ceterol in animals: cholesterol, is both the structural component of membranes and the precursor compound of many steroids. Cholesterol is the principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell membranes. Other biologically active lipids Phosphophatidylinositols and sphingosine derivatives act as intracellular signals ◦ Extracellular signals activate the specific phospholipase C in the membrane, which hydrolyzes phosphadidinositol 4.5-bisphosphate and releases the intracellular messengers water-soluble inositol 1,4,5-triphostate (IP3) and diacylglycerol. IIP3 triggers Ca2+ release from the ER. The combination of Ca2+ and diacylglycerol activates the protein kinase C enzyme. Other biologically active lipids Eicosanoids carry messages to nearby cells. ◦ They are paracrine hormones and act only in cells close to hormone synthesis points. ◦ They are derivatives of fatty acids. ◦ They take part in the inflammatory process that occurs after infection or injury. ◦ They play a role in regulating smooth muscle contraction ◦ They are not stored; They are synthesized when needed ◦ It is the name given to hormones (Prostaglandin, thromboxane and leukotriene) made from the 20- carbon polyunsaturated fatty acid arachidonate. Prostoglandin (PG) Prostaglandins are lipid components derived enzymatically from fatty acids that have important functions in the body of animals. Prostaglandins contain 20 carbon atoms and a 5-carbon ring. There are 2 specific groups: PGE (ether soluble) and PGF (phosphate buffer soluble). Prostaglandins are potent, locally acting vasodilators and prevent the aggregation of platelets that enable blood clotting. Prostaglandins also participate in inflammation. They can increase body temperature and cause pain. It has a role in the sleep-wake cycle. Prostaglandins support the regulation of the reproductive system in women. They can induce labor and control ovulation. They stimulate the contraction of smooth muscles in the uterus during menstruation and birth. Thromboxanes They are produced by platelets Unlike prostaglandins, thromboxanes are vasoconstrictors and facilitate the aggregation of platelets necessary for clotting. It functions to reduce blood flow in the clot area. Non-steroidal anti-inflammatory drugs such as aspirin and ibuprofen prevent the formation of PG and thromboxane from arachidonate (the precursor of PG and thromboxane). Leukotrienes Leukotrienes are chemical mediators that powerfully activate the immune response. Leukotriene D4, derived from Leukotriene A4, causes contraction of the smooth muscles lining the airways in the lung. Its excessive production causes asthma attacks. ◦ Leukotriene synthesis is the target of drugs developed against asthma. (ex: prednisone) Other biologically active lipids Steroid hormones carry messages between tissues. ◦ They are carried through the bloodstream. ◦ Hormones bind to their receptors with high specificity. (effective even in nanomolar amounts) ◦ Steroids derived from cholesterol ◦ Testosterone, Estradiol, produced by the adrenal cortex; Cortisol (glucose metabolism), Aldosterone (salt secretion) ◦ Prednisolone and prednisone are synthetic steroids used as anti-inflammatory agents.