Bioc2014 Macromolecules/Chemical Bonding PDF

BIOC2014 MACROMOLECULES/ CHEMICAL BONDING DR. BRYAN  What are Macromolecules? Large, carbon-based organic molecules. Created by polymerization of smaller subunits. Four major types: 1. Carbohydrates – monosaccharides 2. Proteins – amino acids 3. Nucleic acids – nucleotid...

BIOC2014 MACROMOLECULES/ CHEMICAL BONDING DR. BRYAN  What are Macromolecules? Large, carbon-based organic molecules. Created by polymerization of smaller subunits. Four major types: 1. Carbohydrates – monosaccharides 2. Proteins – amino acids 3. Nucleic acids – nucleotides 4. Lipids- no true basic units = fatty acids + glycerol Body can obtain energy from carbohydrates, lipids and proteins but carbohydrates are used first, if available. 2  CARBOHYDRATES Primary source of energy. Oxidation of carbohydrates during respiration yields energy which is stored in ATP and utilized whenever needed. Structural components (cell membrane) Part of backbone of nucleic acids (DNA and RNA) Role in cell identification, signaling 3  CARBOHYDRATES Carbohydrates are carbon-based molecules rich in hydroxyl groups and thus are known as polyhydroxy aldehydes and ketones. Most abundant carbohydrate is glucose, C6H12O6 and is the most important simple carbohydrate in human metabolism. 4  CLASS QUESTION General empirical formula is Cn(H2O)n. Question: If a carbohydrate has 5 carbons, what would be its molecular formula? 5 CLASSIFICATION OF MONOSACCHARIDES Monosaccharides are classified based on either number of carbon atoms or characteristic carbonyl group. According to the number of carbon atoms: Trioses, tetroses, pentoses, hexoses, heptoses, octoses. According to the characteristic carbonyl group: Aldehyde group or ketone group. 6  MONOSACCHARIDES The most common monosaccharides have 3-8 carbon atoms. The suffix –ose indicates that a molecule is a ‘sugar’- carbohydrate. The prefixes tri-, tetr-, pent- etc indicate the number of carbon atoms in the monosaccharide. 7  Classification of Carbohydrates Simple Carbohydrates Monosaccharides (single sugar unit) Disaccharides (2 sugar units) Complex Carbohydrates Oligosaccharides (3 to 10 sugar units) Polysaccharides (10 or more sugar units) 8  CLASSIFICATION OF CARBOHYDRATES Homopolysaccharides- consist of the same monosaccharides (eg. starch, cellulose) Heteropolysaccharides- different monosaccharides (eg. hyaluronic acid) 9  MONOSACCHARIDES Aldo sugars: Aldoses Monosaccharides containing aldehyde group eg. glucose, ribose. Keto sugars: Ketoses Monosaccharides containing ketone group eg. fructose, ribulose. 10  Classification of Carbohydrates An aldose has the carbonyl on C1 (aldehyde). A ketose has the carbonyl on C2 (ketone). Since a 4-Carbon sugar is a tetrose, then an aldotetrose is a 4-Carbon sugar that contains an aldehyde functional group. 11 Identify the aldose or ketose below: Straight chain structures 10 12  Monosaccharide Structures Straight chain structures glyceraldehyde ribose glucose fructose 13  MONOSACCHARIDES Simpliest monosaccharides are two 3- Carbon trioses: Glyceraldehyde (an aldotriose) Dihydroxyacetone (a ketotriose) Except for glyceraldehyde and fructose, most of the carbohydrates of interest in human biochemistry are aldohexoses or aldopentoses. 14 NOTE: When naming four and five carbon ketoses they are designated by inserting “ul” into the name of the corresponding aldose. Eg. ribose becomes ribulose (ketose form). 15 MONOSACCHARIDES: STRUCTURE 16  MONOSACCHARIDES: STRUCTURE Monosaccharides possess stereogenic centres: mostly carbon atoms that bind four different groups are often called ‘asymmetric (chiral)’ carbon atoms. All carbohydrates contain at least one asymmetrical (chiral) carbon. Exception: Dihydroxyacetone which has no chiral carbon. 17 MONOSACCHARIDES: STRUCTURE 18  MONOSACCHARIDES: STRUCTURE Glyceraldehyde (a chiral molecule) is used as the standard reference molecule. The presence of asymmetric carbon atoms confers optical activity. Rotates polarized light to the: right (D)- Dextrorotatory or to the left (L)- Levorotatory. D-glyceraldehyde and L-glyceraldehyde are stereoisomers. 19  MONOSACCHARIDES: STRUCTURE They differ in the configuration about the chiral carbon that is the furthest from the carbonyl carbon. 20 α- and β- anomers (Anomerism) 21  Some important monosaccharides Glucose (C6H12O6) – Most important simple carbohydrate in human metabolism. – Regulation of blood glucose is important in human health. Hormones: insulin and glucagon – Diabetes mellitus  Some important monosaccharides Fructose (C6H12O6): fruit sugar - Structural isomer of glucose -Sweeter than glucose - Fructose intolerance leads to fructose accumulation and hypoglycaemia. 23  Some important monosaccharides Galactose (C6H12O6) – Major source: diary products -milk – Component of lactose (disaccharide) & glycoproteins found in brain and nerve tissue. – Galactosemia: excess galactose results in Cataract due to enzyme deficiency.  Biological Significance Most of the monosaccharides in humans are D-sugars. There are some important sugars however, that occur in the L- form. For example, L-arabinose and L-fucose found in glycoproteins of plants and mammalian cells respectively. *NOTE: Only L-amino acids are used in protein synthesis. 25  Disaccharides- Chemical Bond Formed via condensation/dehydration reactions: - A H20 molecule is removed (condensation) from a pair of monosaccharide molecules when joined together. - The bond formed between 2 monosaccharides is called a glycosidic bond (O-glycosidic bond). Disaccharides may be hydrolyzed to form monosaccharide subunits (reverse reaction). 26 27 Examples of Disaccharides: Sucrose Commonly called “table sugar”. Composed of glucose and fructose through an α(12)β glycosidic bond. Highly sweet and soluble. 28 Example of a Disaccharide - Sucrose (non-reducing sugar) 29  Maltose Disaccharide with a α(14) glycosidic linkage between one glucose and a second glucose. It is called “malt sugar”. Intermediate product of the hydrolysis of starch. 30 31  Lactose Found exclusively in the milk of mammals, so it is called “milk sugar”. Consists of galactose and glucose in a β (14) glycosidic bond. It is less sweet and less soluble. 32 33  Oligosaccharides Oligo means “few” Contains 3-10 monosaccharide molecules which are liberated on hydrolysis. Functions include cell recognition and cell adhesion in the cell membrane. Not commonly found free in cells but rather covalently attached to proteins and thus are said to be glycosylated. When attached to proteins are by N- or O-glycosidic bonds. 34  Examples of Oligosaccharides Trisaccharides: Contains 3 monosaccharide units eg. Raffinose  Fructose+Galactose+Glucose Tetrasaccharides: Contains 4 monosaccharide units eg. Stachyose  2 (Galactose)+Glucose+Fructose Pentasaccharides: Contains 5 monosaccharide units eg. Verbascose  3 (Galactose)+Glucose+Fructose 35  Blood groups ABO substances are oligosaccharides present in most cells of the body and in certain secretions. On the surface of red blood cells, three different types of oligosaccharides may be found. These help provide the ABO blood group determinants. 37  All have a chain of four sugars, they are written: gal - nag - gal - fuc which represents galactose, n-acetylglucosamine, and fucose. Fucose is a 6-carbon L-sugar. 38  Polysaccharides Large molecules > 10 monosaccharide units. Joined by O-glycosidic linkages in one continuous chain or the chain may be branched. 1. Storage polysaccharides: Contain only α- glucose units. e.g. starch and glycogen 2. Structural polysaccharides: Contain only β- glucose units. eg. cellulose and chitin. 39  POLYSACCHARIDE -STARCH Main food storage molecule of plants. Mixture of 2 polymers: amylose (20%) amylopectin (80%) Amylose: glucose units linked by α-1,4 glycosidic bonds. Long and unbranched Amylopectin: glucose units linked in short chains by α-1,4 glycosidic bonds. Branched every 24 - 30 glucose units Branches formed by 1,6 glycosidic bonds 40  Structure of Starch: Amylose & Amylopectin 1-4 bond 1-6 bond 1-4 bond 41  HOMOPOLYSACCHARIDES - GLYCOGEN Glycogen is a readily mobilized storage form of glucose. Large, branched polymer of glucose residues that can be broken down to yield glucose molecules when energy is needed by the body. Structure is identical to amylopectin, except that the α-(1,6) branching occurs about every 12 glucose units. 42 https://www.slideshare.net/adityavamsipalepu/carbohydrate-ppt HOMOPOLYSACCHARIDES - GLYCOGEN 43 GLYCOGEN 44  HETEROPOLYSACCHARIDES Commonly called glycosaminoglycans (GAGs) or mucopolysaccharides. Long, unbranched chains generally composed of a repeating disaccharide unit (amino sugar-acidic sugar)n Amino sugar: D-acetyl glucosamine or D-galactosamine Acidic sugar: D-glucuronic acid or L-iduronic acid Examples: chitin, hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate and heparin. 45  Examples: CHITIN Second most abundant polysaccharide in nature. Exoskeleton of crustaceans and insects: lobsters, beetles and spiders Made of N-acetylglucosamine containing: β (1--4) glycosidic bonds. Chitin is used as surgical thread that biodegrades as a wound heals. 47  Hyaluronic acid (Hyaluronate) Long chains of modified glucose units are found in synovial fluid in joints, eye and in connective tissues (ligaments, cartilage, skin). Viscous molecule that provides lubrication and shock absorption.  Chondroitin 6-sulphate Repeating disaccharide units composed of glucuronic acid and N-acetylgalactosamine. Chains are found in connective tissues, tendons and cartilage (also used in artificial skin).  Recommended for the prevention and management of osteoarthritis.  Heparin Polysaccharide polymer consisting of 2 types of monosaccharides: uronic acid and glucosamine It is an anticoagulant used in preventing blood clotting after surgery and in blood sample tubes. 51 52 53 54  PROTEINS Large complex molecules composed of amino acids. 20 different amino acids used to make proteins. essential (9) - must be supplied by food non-essential (11) – can be made in the body FUNCTIONS: Structural components- building blocks of muscle, bone, skin and hair. Proteins used in the body to build, maintain and repair the tissues in the body. As enzymes, hormones, antibodies, transport and signal molecules. 55 AMINO ACID STRUCTURE 56  PROTEINS Amino acids are linked together in a specific sequence by peptide bonds. The sequence of amino acids is determined by DNA. 2 amino acids = dipeptide (1 peptide bond) Short chains of amino acids, generally containing fewer than 10 amino acids are referred to as peptides. Longer chains of amino acids up to 50 amino acids are referred to as polypeptides. 57  PEPTIDE BOND FORMATION Peptide bonds are formed by a condensation reaction- removal of a molecule of water. 58 59 PROTEIN STRUCTURE 60  LIPIDS Lipids are usually non-polar, hydrophobic, water insoluble substances of diverse structure with a wide variety of important functions related to structure. Has less oxygen, more C-H bonds than carbohydrates. Significant source of energy: Lipids contain twice the energy content as carbohydrates. Lipids are the constituents of cell membranes and regulate membrane permeability. Shock absorbers for internal organs. Thermal insulation. 61 EXAMPLES OF LIPIDS 62  NUCLEIC ACIDS Biopolymers that are essential to all forms of life. Direct cellular activities such as cell division and protein synthesis. Two main classes of nucleic acids: DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) Basic units of nucleic acids are nucleotides. BIOLOGICAL ROLE OF NUCLEOTIDES: 1. Genetic information 2. Energy carrier (eg. ATP and GTP) 3. Components of co-enzymes (eg. NAD and FAD) 4. Signal transduction 63  RIBOSE DEOXYRIBOSE The sugar molecule in DNA and RNA is ribose. However, in DNA the ribose sugar lacks oxygen at C-2 and hence it is called deoxyribose. 64  NUCLEIC ACIDS Nucleotides consists of a phosphate group – sugar molecule – nitrogenous base 65 WHAT ATOM IS THIS? 66  CHEMICAL BONDING All life forms are based on the bonding properties of the element Carbon, and is therefore a very important atom in the biological sciences. Why? Because it forms very stable bonds with itself and with other atoms such as: hydrogen (H), nitrogen (N) and oxygen (O) Biological macromolecules are organic- contain carbon. They may also contain hydrogen, oxygen, nitrogen, phosphorous, sulfur and other elements. 67  What is Chemical Bonding? A lasting attraction between atoms, ions or molecules that enables the formation of chemical compounds. May result from the electrostatic force of attraction between oppositely charged ions as in ionic bonds or through the sharing of electrons as in covalent bonds. Types of chemical bonds that are important in living systems are covalent bonds and non-covalent interactions. Biological structures and processes depend on the interplay of these two interactions. 68 MAIN TYPES OF CHEMICAL BONDING IN MACROMOLECULES Covalent Bonds: Peptide (amide bonds) Disulfide bonds Non-covalent bonds: Ionic Bonds Hydrogen Bonds Hydrophobic interactions van der Waals forces 69  MACROMOLECULES/CHEMICAL BONDING Macromolecules are held together by strong intramolecular forces such as covalent bonds. Amino acids in proteins, nucleotides in DNA/RNA, sugars in carbohydrates and fatty acids in lipids. Atoms with relatively similar electronegativities share electrons between them and are connected by covalent bonds. 70  EXAMPLES IN MACROMOLECULES- COVALENT BONDING PEPTIDE BOND: This bond links amino acids of proteins together to form dipeptides, tripeptides,--- and polypeptides. 71  EXAMPLES IN MACROMOLECULES- COVALENT BONDING DISULFIDE BOND: Formed between two cysteine residues, this bond can hold two separate polypeptide chains together (inter-chain bonding) or can occur within a single chain (intra-chain bonding). 72  MACROMOLECULES/CHEMICAL BONDING Non-covalent interactions are critically important determinants of biomolecular structure, stability and function. Non-covalent forces play essential roles in the folding of proteins into three-dimensional forms, specific recognition of substrates by enzymes, the detection of molecular signals and replication of DNA. Three fundamental non-covalent bonds: electrostatic interactions, hydrogen bonds, and van der Waals interactions. 73 Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002. Section 1.3, Chemical Bonds in Biochemistry. Available from: https://www.ncbi.nlm.nih.gov/books/NBK22567/  IONIC BONDING Atoms with large differences in electronegativity transfer electrons to form ions. The ions then are attracted to each other. This attraction is known as an ionic bond. Proteins are also stabilized by ionic bonds. This is not hard to visualize as the side chains of some amino acids are positively charged and the side chains of others are negatively charged. 74 EXAMPLES IN MACROMOLECULES- IONIC BONDING Bonding between two amino acids: R1-CH(NH)COO– & + H3NCH(COOH)-R2 75  HYDROGEN BONDING A chemical bond in which a hydrogen atom of one molecule is attracted to an electronegative atom, generally a nitrogen, oxygen or fluorine atom. Crucial for biological macromolecules such as DNA and proteins. Also responsible for the many properties of water that makes it such a universal solvent. Water is the single most abundant component of cells and organisms. 70-85% of a cell by weight is water.  POLAR NATURE OF WATER Hydrogen bonds between water molecules = electrostatic attraction between the oxygen atom of one water and the hydrogen of another. The polar nature and geometry of the water molecule allows water molecules to form hydrogen bonds with each other and with functional groups of hydrophilic (polar or ionic) biomolecules and organic compounds. Nearly all biological molecules assume their shapes and functions in response to the physical and chemical properties of the surrounding water. 77 78 79 80  Hydrogen bonding in Important Biological molecules Proteins: Hydrogen bonding takes place within a protein molecule and between protein molecules. This stabilizes the protein molecule. DNA: The stabilization of the double helix is due to the hydrogen bonding between: guanine & cytosine (G - C) base pairs having 3 hydrogen bonds adenine & thymine (A - T) base pairs having 2 hydrogen bonds 81 HYDROGEN BONDING- PROTEINS 82 HYDROGEN BONDING- DNA 83  HYDROPHOBIC INTERACTIONS: Describes the relations between water and hydrophobes (low water-soluble molecules). Hydrophobes are non-polar molecules which usually have a long chain of carbons that do not interact with water molecules. Hydrophobic effect is the observed tendency of non-polar substances to aggregate in an aqueous solution and exclude water molecules. Example of hydrophobic interactions include the folding of the tertiary structure in proteins and the specific double helical structure of DNA. Proteins fold in such a way that hydrophobic amino acids are located in the interior of the molecular, away from water. 84 HYDROPHOBIC INTERACTIONS: 85  van der Waals Forces (London dispersion forces) Weak force of attraction between electrically neutral molecules in close proximity to each other. Caused by temporary attractions between electron- rich regions of one molecule and electron-poor regions of another. These bonds along with ionic, covalent and hydrogen bonds contribute to the three-dimensional (3-D) structure of proteins that is necessary for their proper function. CHEMICAL BONDING IN PROTEINS Chemical bonds present: Peptide bonds (primary) Hydrogen bonds (secondary & tertiary) Ionic attraction/bonds (tertiary) Hydrophobic & hydrophilic interactions (tertiary) Disulfide Bridges (tertiary) Quaternary is dependent on the tertiary structure of the individual polypeptides and so is influenced by these bonds. 87 Question: What class of Protein? 88 CLASS ACTIVITY/ASSIGNMENT 89