Chem 43: Carbohydrates and Lipids-2 (PDF)

CHEM 43: Biochemistry I CARBOHYDRATES I. Introduction to Carbohydrates II. Monosaccharides Carbohydrates Aldoses Ketoses C (carbo-) +...

CHEM 43: Biochemistry I CARBOHYDRATES I. Introduction to Carbohydrates II. Monosaccharides Carbohydrates Aldoses Ketoses C (carbo-) + -OH (-hydrate) aldehyde or ketone compounds with multiple hydroxyl groups make up most of the organic matter on Earth Functions: Provide energy (as storage) and metabolic intermediates. Form the structural framework of RNA, DNA, and cell walls (in bacteria and plants) Link with proteins and lipids for cellular functions. have an aldehyde have a keto group, Classification: group at one end usually at C2 Simple Complex Stereoisomerism: D vs L Monosaccharide Oligosaccharide D & L are based on the configuration about glucose, fructose, the single asymmetric C in glyceraldehyde. galactose For sugars with more than one chiral center, D Disaccharide Polysaccharide or L refers to the asymmetric C farthest from lactose, sucrose, starch, glycogen, the aldehyde or keto group. maltose cellulose Simplest carbohydrates: monosaccharides (simple sugars), with the general formula Cn(H₂O)n. Nomenclature of Monosaccharides: Epimerism: differ only in one asymmetric C. Prepared by: Dhenz CHEM 43: Biochemistry I CARBOHYDRATES Prepared by: Dhenz  CHEM 43: Biochemistry I CARBOHYDRATES III. Cyclization of Sugars Fructose forms either: Hemiacetal & Hemiketal Formation a 6-member pyranose ring, by reaction of the C2 keto group with the OH on C6, or a 5-member furanose ring, by reaction of the C2 keto group with the OH on C5. Pentoses and hexoses can cyclize as the ketone or aldehyde reacts with a distal OH. Anomers: Cyclization of glucose creates a new asymmetric center at C1, forming two anomers: α: OH group below the ring. β: OH group above the ring. Haworth projections depict the cyclic structure as a nearly planar ring. Glucose forms an intramolecular hemiacetal, as the C1 aldehyde & C5 OH react, to form a 6-member pyranose ring, named after pyran. Mechanism (Pyranose Formation): Because of the tetrahedral nature of carbon bonds, pyranose sugars actually assume a "chair" or "boat" configuration, depending on the sugar. Prepared by: Dhenz  CHEM 43: Biochemistry I CARBOHYDRATES IV. Sugar Derivatives Sugar alcohol Sugar acid Deoxy Sugars the aldehyde at C1, or OH at C6, An H replaces an OH lacks an aldehyde is oxidized to a N-acetylneuraminate (N-acetylneuraminic acid, or ketone carboxylic acid also called sialic acid) is often found as a terminal residue of oligosaccharide chains of glycoproteins. Amino sugar an amino group substitutes for a Sialic acid imparts negative charge to hydroxyl, which may be acetylated, glycoproteins, because its carboxyl group tends as in N-acetylglucosamine. to dissociate a proton at physiological pH, as shown here. Sugar Phosphates Prepared by: Dhenz  CHEM 43: Biochemistry I CARBOHYDRATES V. Reactions of Monosaccharides Oxidation of Sugars with Bromine Water: 1. Mutarotation: Interconversion of α and β anomer in aqueous solution Oxidation with HNO3: ( Mucic Acid Test) 2. Oxidation to Sugar Acids: provides energy for organisms. For hexoses: with Tollen’s Reagent: Lactones form when aldoses are oxidized with Br2 C1 CHO to COOH Aldonic acid Tollen’s reagent (silver-ammonia complex), e.g., Cr2O7 C6 OH to COOH Uronic acid α-D-glucose is oxidized to a lactone. HNO3 C1 CHO to COOH Aldaric acid C6 OH to COOH Tollen's test: A positive result produces a silver mirror = presence of an aldehyde group. Benedict’s Test: Sugars that react are called 3. Reduction to Sugar Alcohols: aldoses reducing sugars; non reducing for not. (and ketoses) can be reduced with sodium borohydride to compounds called alditols. (+) glucose, (-) sucrose, (+) hydrolyzed sucrose Prepared by: Dhenz  CHEM 43: Biochemistry I CARBOHYDRATES 4. Osazone Formation: aldehyde group of 6. Exhaustive Methylation: R-OH reactions an aldose react with carbonyl reagents such only affect anomeric C’s; other R groups can as hydroxylamine and phenylhydrazine. be methylated using dimethylsulfate. determine glycosidic linkages presence. results in a loss of the stereocenter at C2 but does not affect other stereocenters. Ether Formation: Osazones of Glucose and Mannose: Ester Formation: 7. Esterification (Formation of Sugar Phosphates): OH groups may react with 5. Glycoside Formation (Acetal Formation): acids, acid derivatives, phosphates, etc. When a small amount of HCl (g) is passed into a solution of D-(+)-glucose in methanol: e.g., phosphates esterified to ribose or deoxyribose 8. Esterification (Formation of Sugar Sulfates): Sulfates esterified at c-2, C-4 or C-6 of aldoses; found: proteoglycan of ECM. Presence of sulfate groups mean that sugar is negatively charged at phys. pH. acetal of glucose: → glucoside acetals of mannose: → mannosides ketals of fructose: → fructosides Prepared by: Dhenz  CHEM 43: Biochemistry I CARBOHYDRATES VI. Disaccharides c. Sucrose (table sugar) α(1→2) linkage of anomeric hydroxyl ❖ Composed of 2 monosaccharides linked by group of fructose and glucose glycosidic bond. Full name α-D-glucopyranosyl- (1→2)- β-D-fructopyranose. d. Lactose (milk sugar) β(1→4) linkage of anomeric hydroxyl group of galactose and glucose. Full name: β-D-galactopyranosyl- (1→4)-α-D-glucopyranose. VII. Polysaccharides play vital roles in energy storage, and in maintaining structural integrity of an organism. Examples: Homopoly Heteropoly a. Maltose: from starch (e.g., amylose), all of the monosacc- >1 type of monosacc-, α(1→4) glycosidic bond, C1 of one are the same, e.g., usually 2 alternating glucose to C4 OH of the other. starch, glycogen monosacc- units Glycosidic bonds determine polysacc- structure. α-anomer: C1 oxygen pointing downward. b. Cellobiose: from cellulose breakdown β(1→4) glycosidic bond, where one glucose unit is flipped relative to the other, depicted as a zig-zag. ➔ β-1,4 linkages favor straight chains, which are optimal for structural purposes ➔ α-1,4 linkages favor bent structures, which are more suitable for storage. β-anomer: C1 oxygen pointing upward. Prepared by: Dhenz  CHEM 43: Biochemistry I CARBOHYDRATES (1) Starch (nutritional reservoir in plants): (4) Chitin: main component of the Makes up >50% of carbohydrates ingested exoskeletons of arthropods. by humans. long-chain polymer: N-acetylglucosamine. Forms: (both rapidly hydrolyzed by α-amylase) a. Amylose (unbranched): consists of glucose residues in α-1,4 linkage. (5) Dextran: similar to amylopectin. b. Amylopectin (branched): has α-1,6 Its main chains are formed by α(1→6) linkage per 30 α-1,4 linkages. (less dense glycosidic linkages, with side branches compared to glycogen). attached via α(1→3) or α(1→4) linkages. found in dental plaque and is used as a food additive and as a plasma volume expander. (2) Glycogen: 2 chains of glucose molecules joined by α-1,4-glycosidic bonds linked by α-1,6-glycosidic bond to branch, which forms per 10 glucose (3) Cellulose: the other major polysaccharide of glucose in plants. It is an unbranched polymer of glucose residues linked by β-1,4-glycosidic bonds. Cellulose serves a structural role rather than a nutritional one. Mammals lack cellulases and, therefore, cannot digest wood or vegetable fibers. Prepared by: Dhenz  CHEM 43: Biochemistry I CARBOHYDRATES VIII. Others (8) Glycosaminoglycans: have disaccharide repeating units containing a derivative of (6) Peptidoglycan: make up bacterial cell an amino sugar (either glucosamine or walls; prevents bacteria from bursting in galactosamine). response to their high internal osmotic pressure (mechanical support). At least one of the sugars in the repeating unit has a negatively charged carboxylate or sulfate group. Usually attached to proteins to form proteoglycans. Major Examples: Linear polysaccharide chains cross-linked by short peptides. Penicillin inhibits cross-linking transpeptidase. (9) Proteoglycans: almost all GAGs (7) Glycoproteins: proteins that contain covalently attached to protein in the form oligosaccharide chains covalently attached of proteoglycans (found in animal cells) to their polypeptide side-chains. distinguished from other glycoproteins by Sugars may be attached to: (proteins) the nature, quantity, and arrangement of ○ N in asparagine side chain (N-linkage) their sugar side chains. ○ O in side chain of serine or threonine The linkage between a GAG chain and its core protein in a proteoglycan molecule. Glycoproteins Proteoglycans contain 1–60% can contain as much Example: carbohydrate by wt. as 95% carbs by wt. elastase, a secreted numerous relatively most carbs = long, glycoprotein, showing short, branched unbranched GAG linked carbohydrates on oligosaccharide chains, each typically its surface. chains ~ 80 sugars long Prepared by: Dhenz  CHEM 43: Biochemistry I CARBOHYDRATES Proteoglycan Functions: Blood Group Antigens Proteoglycans and glycosaminoglycans (GAGs) can assemble into large polymeric complexes within extracellular matrix (ECM). GAG chains form gels with: varying pore sizes and different charge densities These gels act as selective sieves, regulating the movement of molecules and cells based on: size, charge, or both. Proteoglycans associate with fibrous matrix proteins (e.g., collagen) to maintain ECM Carbohydrates attached to glycoproteins structural integrity. and glycolipids on the surfaces of red blood cells (RBCs) serve as antigenic determinants. These determinants define blood group antigens (e.g., ABO system). If an antigen not naturally present in a (10) Aggrecan: major component of cartilage. person is introduced (e.g., through transfusion), the immune system MW~ 3×10^6 daltons w/ >100 GAG chain recognizes it as foreign and mounts an immune response. (11) Decorin: secreted by fibroblasts. has a single GAG chain Prepared by: Dhenz