Biochemistry IV Carbohydrates (PDF)

IV. CARBOHYDRATES  A. COMPOSITION AND CLASSIFICATION Carbohydrates are organic molecules / biomolecules that are composed of repeating units of C, H, and O Carbohydrates are classified as monosaccharides, oligosaccharides, and polysaccharides  MONOSACCHARIDES - Compose...

IV. CARBOHYDRATES  A. COMPOSITION AND CLASSIFICATION Carbohydrates are organic molecules / biomolecules that are composed of repeating units of C, H, and O Carbohydrates are classified as monosaccharides, oligosaccharides, and polysaccharides  MONOSACCHARIDES - Composed of C, H, and O that are mostly characterized by the general formula (CH2O)n where n is any integer from 3 to 7 - They are named on the basis of the functional group that they contain: a monosaccharide with a ketone group (-CO) is called as ketose while one with an aldehyde group (-CHO) is called as aldose - Because monosaccharides also contain many hydroxyl groups, they are also sometimes called as polyhydroxyaldehydes or polyhydroxyketones - Another method by which monosaccharides are named is based on the number of carbon atoms in the main skeleton: a 3-C monosaccharide is called a triose, a 4-C is called a tetrose, a 5-C is called a pentose, a 6-C is called a hexose, and a 7-C is called a heptose. - When the functional groups and the no. of C in the carbohydrate backbone shall be both considered, the following names shall be derived: - For the ALDOSES: - with 3 C: aldotriose / glyceraldehyde - with 4 C: aldotetrose - with 5 C: aldopentose, and so on. - For the KETOSES: - with 3 C: ketotriose / dihydroxyacetone - with 4 C: ketotetrose - with 5 C: ketopentose, and so on. - There are certain monosaccharides that do not necessarily follow the general formula (CH2O)n and are chemically modified - Monosaccharides of blood group antigens, bacterial cell wall (with amino groups), intermediates in carbohydrate metabolism (with phosphate groups) - According to stereochemistry, which is the study of the different spatial arrangement of molecules, monosaccharides may also exist as stereoisomers. - Stereoisomers are the two forms of a compound. These two forms therefore have the same molecular formula and same bonding, and differ only on the way they rotate plane-polarized light. One form, called the D-form, (D for dextrorotary) rotates light in a clockwise direction while the other one called L-form (L for levorotary), rotates light in a counterclockwise direction. - Stereoisomers are also called as enantiomers if they are non-superimposable mirror images of each other. Enantiomers are also called as chiral molecules - those that exist as two non- superimposable mirror images - Emil Fischer differentiated D forms from L forms based on the location of the hydroxyl group of the chiral carbon- the carbon located next to the last one at the end opposite to the location of the functional group. D forms have their hydroxyl group located on the right side of the chiral carbon while the L ones are on the left side. - Almost all carbohydrates in living systems are in their D forms.  Significance of stereochemical purity in the medical industry: In 1960, thalidomide, a drug commonly prescribed in Europe as a sedative, resulted into pregnant women who took the drug bearing children with severe birth defects. It turned out that thalidomide has two enantiomers- a sedative and a mutagen called teratogen - Antihistamines are effective decongestants and anti-allergies but also cause drowsiness because its enantiomers are that- one is a decongestant, the other is sleep-inducing - The ibuprofen currently sold in the market is a mixture of isomers, but one is a more effective analgesic than the other  Biologically-important Monosaccharides The most common monosaccharides in biological systems are the five- and six- carbon sugars: glucose, fructose, galactose (6-C); and ribose, and deoxyribose (5-C).  Glucose - The most important sugar in the human body - Found in numerous food - Has several common names: dextrose, grape sugar, and blood sugar - Broken down during glycolysis and other pathways to release energy for body functions - Its concentration is critical to normal body function and is controlled by the hormones insulin and glucagon; normal blood glucose levels are 100 to 120 mg / mL with the highest concentration appearing after a meal - Glucose is an aldohexose and with molecular formula C6H12O6. It may either be in open (Fischer projection) or cyclic form (Haworth projection) - It exists in physiological conditions in its cyclic form because the aldehyde group of C-1 reacts with the hydroxyl at C-5 to give a six-member ring. - The cyclic form of glucose is called a cyclic intramolecular hemiacetal, since a hemiacetal is formed when an aldehyde reacts with an alcohol or hydroxyl. - Cyclic D-glucose forms two isomers – the α- and β-D- glucose. These isomers differ from each other in terms of the location of –OH attached to the hemiacetal carbon. Such isomers, differing in the arrangement of bonds around the hemiacetal carbon, are called anomers. In the α-anomers, the C-1 hydroxyl group is below the ring, and on the β-anomers, the C-1 hydroxyl group is above the ring.  Fructose - Also called as levulose or fruit sugar - Considered as the sweetest sugar - Found in large amounts in honey, corn syrup, and sweet fruits - Similar in structure to that of glucose except that there is CH2OH instead of CHO at C-1 and a ketone group instead of CHOH at C-2. - Thus, fructose is a ketose; its C-2 ketone group reacts with the C-5 hydroxyl group to produce an cyclic intramolecular hemiketal.  Galactose - Found in biological systems as a component of the disaccharide lactose or milk sugar - Component of blood group antigens along with its modified form: β-D-N- acetylgalactosamine  Ribose and Deoxyribose - Ribose is a 5-C sugar that serves as component of RNA and various coenzymes - Deoxyribose has its –OH group in one of its C replaced by a hydrogen. Eg., 2- deoxyribose, the sugar found in DNA, has its –OH group in C-2 replaced by hydrogen  OLIGOSACCHARIDES - Oligosaccharides are carbohydrates that are composed of 2 to 10 chemically bonded monosaccharide units - The most metabolically active oligosaccharides are the disaccharides - consist of two monosaccharides joined together by a glycosidic bond; a glycosidic bond is a carbon-oxygen bond between either a hemiacetal or hemiketal of the first monosaccharide and any of the hydroxyl groups on the second monosaccharide - Biologically important disaccharides include maltose, lactose, and sucrose  Maltose - Also called as malt sugar - One of the intermediates in the hydrolysis of starch - A disaccharide formed through the bond between an α-D-glucose and a β- D-glucose - The bond formed is an α (1→4) glycosidic bond  Lactose - Also known as milk sugar; the principal sugar in the milk of most mammals - Made up of one molecule of β-D-galactose and one of either α- or β-D-glucose (galactose differs from glucose only in the configuration of the hydroxyl group at C-4 such that in the cyclic form of glucose, the C- 4 hydroxyl group is “down” and the C in the galactose, it is “up.”) - The bond is a β(1-4) glycosidic bond - May be used by the body as energy source when it would be hydrolyzed to glucose and galactose - The liberated glucose may be used as direct energy source while galactose must be further converted into glucose before it becomes an energy source - Galactosemia- a genetic disease caused by the lack of enzyme to metabolize galactose; results into severe mental retardation, cataracts, and early death; galactosemic infants must be provided with a galactose-free diet - Lactose intolerance- inability to hydrolyze lactose due to non-synthesis of enzyme lactase; causes cramping, diarrhea, and dehydration; accumulated lactose tends to be degraded by bacteria, upon which CO2 is released, and causes further discomfort; lactose-intolerant individuals must have a lactose-free diet  Sucrose - Also called as table sugar, cane sugar, or beet sugar - Water-soluble and could therefore be easily transported during circulation - May be used as a preservative when present in high concentration because it produces a high osmotic pressure that inhibits bacterial growth - Widely used as a sweetener - A disaccharide of α-D-glucose and β-D fructose - The bond is called as (α1→β2) glycosidic bond  POLYSACCHARIDES - Sugars composed of monosaccharide units (monomers) that have been joined in one or more chains - Three of the most biologically important polysaccharides are starch, glycogen, and cellulose  Starch - Principal storage form of carbohydrate in plants - Found in all plant cells, and in some parts, such as the seed, it may consist of up to 80% of the total dry weight - A heterogeneous material composed of polymers amylose and amylopectin - Amylose accounts for about 80% of the starch of a plant cell - A linear polymer of α-D-glucose molecules connected by glycosidic bonds between C-1 of the 1st glucose and C-4 of the 2nd. Thus, the bonds are specifically called as α (1→4) glycosidic bonds - A single chain may contain up to four thousand glucose units - It coils up into a helix that repeats after every six glucose units Structure of Amylose - Amylose is degraded by two types of enzymes- the α- and β-amylase and are produced in two areas: the pancreas and the salivary gland - The α-amylase cleaves the glycosidic bonds of amylose chains at random along the chain, producing shorter polysaccharide chains - The β-amylase sequentially cleaves the disaccharide maltose from the functional group end of the amylose chain - Maltose is hydrolyzed into glucose by the enzyme maltase and glucose is quickly absorbed by intestinal cells and is later on used by all the other cells of the body as energy source - Amylopectin is a highly branched amylose in which the branches are attached to the C-6 hydroxyl groups by α(1→6) glycosidic bonds - The main chains consist of α(1→4) glycosidic bond - Each branch contains 20-25 glucose units and there are so many branches such that the main chain can scarcely be distinguished Structure of Amylopectin Structure of Starch  Glycogen - The major glucose storage molecule in animals - It is stored in the liver and in skeletal muscles - Its regulated synthesis and degradation are involved in keeping blood glucose level constant - Its structure is similar to that of amylopectin, only that its branches are shorter and more numerous - The main chain is linked by α(1→4) glycosidic bonds, and contains many α(1→6) glycosidic bonds that provide many branch points along the chain Structure of Glycogen  Cellulose - Considered as the most abundant polysaccharide in the world - A structural component of the plant cell wall - A polymer of β-D-glucose units linked by β(1→4) glycosidic bonds - A molecule typically contains about 3000 glucose units, but the largest known consists of 26,000 units and is produced by the alga Valonia - Composed of fibrils- long, straight and parallel glucose molecules that make cellulose rigid and an effective protective structure - Cannot be digested by humans since we do not synthesize the enzyme cellulase which can hydrolyze the β(1→4) glycosidic linkages of the polymer. - Can be digested by animals such as termites, cows, and goats because of their microflora that secretes cellulase. Structure of Cellulose Cellulose in Plants  B. FUNCTIONS / SIGNIFICANCE - Produced in plants by photosynthesis and found in grains, cereals, breads, sugar cane, fruits, milk, and honey - Important source of energy for animals - Glucose, in particular, is the primary energy source for the brain and nervous system and can be used by many other tissues - When burned by cells for energy, each gram of carbohydrate releases four kilocalories of energy - Calories are a measure of the energy and heat content that can be derived from food - 1 food calorie ( C ) = 1000 calories = 1 kilocalorie - 3500 Calories are equivalent to approximately 1 pound of body weight- one has to take in 3500 Calories more than what is taken in to gain a pound, and one has to expend 3500 Calories more than what is used to lose a pound A frequently recommended procedure for increasing the rate of weight loss involves a combination of dieting and exercise. The number of Calories used in several activities are as follows: Activity Energy Output (C/min) Running 19.4 Swimming 11.0 Jogging 10.0 Bicycling 8.0 Tennis 7.1 Walking 5.2 Golfing 5.0 Driving a car 2.8 Standing or Sitting 1.9 Sleeping 1.0 A healthy diet should contain both complex carbohydrates (starch and cellulose) and simple sugars in the right amount. Taking in of simple sugars such as sucrose must be minimized because large quantities of this sugar promote tooth decay, obesity, and diabetes. It is recommended that about 58% of the calories in one’s diet should come from complex carbohydrates and that no more than 10% of the daily caloric intake should be sucrose.  C. Metabolism Metabolism is any chemical activity that occurs within a living system. It consists of two phases- anabolism and catabolism. Anabolism is biosynthesis while catabolism is the degradation of fuel molecules, such as carbohydrates. The cell, through a series of enzymes, carries out biochemical pathways that involves a step-by-step oxidation of glucose (686 Calories / mole of glucose is released in a complete oxidation process). Several points in the pathway releases small amounts of energy, these amounts are harvested and saved in the bonds of a molecule called as the universal energy currency – adenosine triphosphate (ATP). ATP: The Cellular Energy Currency - Serves as a “go-between” molecule that couples the exergonic and endergonic reactions - A nucleotide – composed of a nitrogenous base; a 5-carbon sugar; and one, two, or three phosphoryl groups - Has a phosphoester bond that joins the first phosphoryl group to ribose and two phosphoanhydride bonds that link the next two phosphoryl groups to the first one. - A phosphoanhydride bond is a high energy bond that when broken or hydrolyzed, releases a large amount of energy; in ATP’s case, the energy that is released can be used for cellular work Molecular Structure of ATP  ATP Synthesis involves phosphorylation – the addition of phosphate into a molecule Types of Phosphorylation – Photophosphorylation – light energy stimulates electron flow, creating an ion gradient which the enzyme ATP synthase uses to generate ATP – Substrate-level Phosphorylation – an enzyme transfers a phosphate group from ADP to ATP and may happen with or without oxygen – Oxidative Phosphorylation – similar to photophosphorylation except that its energy source is not light but the oxidation / loss of electrons of NADH Hydrolysis of ATP 1. Major Metabolic Pathways- Catabolism Catabolism begins with the supply of nutrients and is composed of the following: Stage 1. Hydrolysis of Dietary Macromolecules into Small Sub-units - Polysaccharides are hydrolyzed into monosaccharides via the use of the following enzymes: amylase, maltase, sucrase, lactase, and galactase - The monosaccharides are then taken up by the epithelial cells of the small intestines via active transport Stage 2. Conversion of Monomers into a Form that can be Completely Oxidized - assimilation of monosaccharides into the pathways of energy metabolism such as cellular respiration where glucose or fructose becomes converted into acetyl CoA  Stage 3. The Complete Oxidation of Nutrients and the Production of ATP - Entering of acetyl CoA to the citric acid cycle where its electrons and hydrogen atoms are harvested during the complete oxidation of the acetyl group to CO2 and are used in oxidative phosphorylation to produce ATP  Cellular Respiration Biochemical pathway that leads on to the complete oxidation of glucose into carbon dioxide and water and the release of ATP May either be aerobic or anaerobic Aerobic respiration occurs in the presence of oxygen and consists of glycolysis, citric acid cycle, and the electron transport chain Anaerobic respiration happens without oxygen and is composed of glycolysis and fermentation Aerobic Cellular Respiration Aerobic Cellular Respiration  Glycolysis - Also known as Embden-Meyerhof Pathway - The first successful energy-harvesting pathway that evolved on the Earth - May occur with or without oxygen and are carried out in the cell’s cytoplasm that contains the needed enzymes - Involves substrate-level phosphorylation  Reactions of Glycolysis Reaction 1: glucose + ATP → glucose-6-phosphate + ADP + H+ enzyme: hexokinase Reaction 2: glucose-6-phosphate → fructose-6-phosphate enzyme: phosphoglucose isomerase Reaction 3: fructose-6-phosphate + ATP → fructose-1,6-biphosphate + ADP + H+ enzyme: phosphofructokinase Reaction 4: fructose-1,6-biphosphate → dihydroxyacetone phosphate + glyceraldehyde-3-phosphate enzyme: aldolase Reaction 5: dihydroxyacetone phosphate → glyceraldehyde-3- phosphate enzyme: triose phosphate isomerase  Reaction 6: glyceraldehyde-3-phosphate + NAD+ + Pi → 1,3-biphosphoglycerate + NADH + H+ enzyme: glyceraldehyde-3-phosphate dehydrogenase Reaction 7: 1,3-biphosphoglycerate + ADP + H+ → 3-phosphoglycerate + ATP enzyme: phosphoglycerate kinase Reaction 8: 3-phosphoglycerate → 2-phosphoglycerate enzyme: phosphoglycerate mutase Reaction 9: 2-phosphoglycerate → phosphoenol pyruvate + H2O enzyme: enolase Reaction 10: phosphoenol pyruvate + ADP + H+ → pyruvate + ATP enzyme: pyruvate kinase  Glycolysis, as a process, yields three important products: – Chemical energy as ATP. 4 ATP molecules are formed by substrate-level phosphorylation which means that a high-energy phosphoryl group from one of the substrates in glycolysis is transferred to ADP to form ATP – Chemical energy in the form of reduced NAD+, NADH. Nicotinamide adenine dinucleotide (NAD+) is a co-enzyme derived from niacin. NADH carries hydride anions which, during aerobic respiration, becomes transported to the mitochondria where they are used to generate ATP through oxidative phosphorylation – 2 pyruvate molecules. These are converted to acetyl CoA destined for citric acid cycle and complete oxidation under aerobic condition and is used as an electron acceptor in fermentation during anaerobic condition Conversion of Pyruvate to Acetyl CoA In the presence of oxygen, pyruvate enters the mitochondria and is converted into a two-carbon acetyl group that becomes activated when the acetyl group is bonded to the thiol group of coenzyme A Coenzyme A is a large thiol derived from ATP and the vitamin panthothenic acid. It is an acceptor of acetyl groups which become bonded to it through a high- energy thioester bond Pyruvate (CH3COCOO-) + Coenzyme A (H – S – CoA) → acetyl Coenzyme A (CH3COSCoA) + CO2 Structure of Acetyl CoA  Citric Acid Cycle - Also called as Kreb’s Cycle - Occurs in the mitochondrial matrix - Releases the following products per mole of acetyl CoA undergoing the process: - 3 moles of NADH - 2 moles of CO2 - 1 mole of FADH2 - 1 mole of GDP  Electron Transport System / Chain - A series of electron carriers, including coenzymes and cytochromes, that carries out a complex process known as oxidative phosphorylation - Oxidative phosphorylation consists of oxidation and reduction reactions that creates a hydrogen ion concentration gradient which drives ATP synthesis - Occurs in the inner mitochondrial membrane - Oxygen is used as an electron acceptor, leading on to the release of water - The last component of the process is a multiprotein complex called ATP synthase  Summary of ATP Yield from Aerobic Respiration Glycolysis substrate level phosphorylation 2 ATP 2 NADH x 2 ATP / cytoplasmic NADH 4 ATP Conversion of 2 pyruvate to 2 acetyl CoA 2 NADH x 3 ATP / NADH 6 ATP Electron Transport Chain from products of Krebs Cycle (for the 2 acetyl CoA) 2 GTP x 1 ATP / GTP 2 ATP 6 NADH x 3 ATP / NADH 18 ATP 2 FADH2 x 2 ATP / FADH2 4 ATP Net Yield 36 ATP  Anaerobic Respiration - Also known as fermentation and is a catabolic reaction that occurs with no net oxidation - Occurs either as lactate or alcohol fermentation - Lactate Fermentation: - Pyruvate is reduced to form lactate as NADH becomes oxidized to NAD+ - Enzyme involved: lactase dehydrogenase - Alcohol Fermentation - Pyruvate is cleaved to acetaldehyde and CO2 - Enzyme involved: pyruvate decarboxylase - Acetaldehyde is reduced to ethanol as NADH becomes oxidized to NAD+ - Enzyme involved: alcohol dehydrogenase  2. Anabolism Gluconeogenesis the production of glucose from non- carbohydrate material occurs primarily in the liver; may also be observed in muscle tissues essentially the reverse of glycolysis pyruvate is converted to phosphoenol pyruvate via the enzymes pyruvate carboxylase which adds CO2 to pyruvate leading into the formation of oxaloacetate phosphoenol pyruvate carboxykinase removes CO2 and adds a phosphoryl group involves dephosphorylation of glucose-6-phosphate which is carried out by the enzyme glucose-6- phosphatase that is produced in the liver but not in the muscle