Carbohydrate Metabolism - PDF

Carbohydrate metabolism Any biochemistry textbook may work, e.g. Lippincott’s Illustrated Reviews, Biochemistry, 3rd ed, Chapters 7-8,10-14 Roskoski, Biochemistry, 1st ed, Chapters 7, 10, 25 Berg, Tymoczko, Stryer, 6th ed, Chapters 11, 16, 20, 21 CARBOHYDRATES Learning objectives: Classify carb...

Carbohydrate metabolism Any biochemistry textbook may work, e.g. Lippincott’s Illustrated Reviews, Biochemistry, 3rd ed, Chapters 7-8,10-14 Roskoski, Biochemistry, 1st ed, Chapters 7, 10, 25 Berg, Tymoczko, Stryer, 6th ed, Chapters 11, 16, 20, 21 CARBOHYDRATES Learning objectives: Classify carbohydrates according to their definitions Discuss isomeric properties of carbohydrates Draw structures of the most common carbohydrates Discuss digestion of dietary carbohydrates  CARBOHYDRATES The most abundant organic molecules in nature Provide a significant fraction of the energy in the diet of most organisms Important source of energy for cells Can act as a storage form of energy Can be structural components of many organisms Can be cell-membrane components mediating intercellular communication Can be cell-surface antigens (ABO, MHC) Can be part of the body’s extracellular ground substance Can be associated with proteins and lipids Part of RNA, DNA, and several coenzymes (NAD+, NADP+, FAD, CoA)  CARBOHYDRATES optically active polyhydroxy aldehydes or ketones, or substances that yield these compounds on hydrolysis Aldehyde group O H C CH2OH Keto H- C - OH C O group CH2OH CH2OH Glyceraldehyde Dihydroxyacetone Carbohydrate with an aldehyde group: Aldose Carbohydrate with a ketone group: Ketose  CARBOHYDRATES Polyhydroxy aldehydes or ketones, or substances that yield these compounds on hydrolysis O H C CH2OH Both can be H- C - OH C O written C3H6O3 or CH2OH CH2OH (CH2O)3 Glyceraldehyde Dihydroxyacetone Empirical formula of many simpler carbohydrates: (CH2O)n (hence the name hydrate of carbon)  Monosaccharides Polyhydroxy aldehydes or ketones that can’t easily be further hydrolyzed “Simple sugars” Number of carbons Name Example 3 Trioses Glyceraldehyde 4 Tetroses Erythrose 5 Pentoses Ribose 6 Hexoses Glucose, Fructose 7 Heptoses Sedoheptulose 9 Nonoses Neuraminic acid  Oligosaccharides Hydrolyzable polymers of 2-10 monosaccharides Disaccharides composed of 2 monosaccharides Examples: Sucrose, Lactose Sucrose= glucose + _______________ Maltose= glucose + ______________ Lactose= glucose + ______________ Trisaccharides composed of 3 monosaccharides Tetrasaccharides composed of 4 monosaccharides  Polysaccharides Hydrolyzable polymers of > 10 monosaccharides Homopolysaccharides: polymer of a single type of monosaccharide Examples: Glycogen, Cellulose Heteropolysaccharides: polymer of at least 2 types of monosaccharide Example: Glucosaminoglycans  ISOMERISM Structural isomers Compounds with the same molecular formula but with different structures Functional group isomers with different functional groups E.g. glyceraldehyde and dihydroxyacetone Positional isomers with substituent groups on different C-atoms E.g. COO--CHOPO3--CH2OH and COO--CHOH-CH2OPO3- 2-Phosphoglycerate 3-Phosphoglycerate  ISOMERISM Stereoisomers Compounds with the same molecular formula, functional groups, and position of functional groups but with different conformations cis-trans isomers with different conformation around double bonds H COOH H COOH C C C C HOOC H H COOH Fumaric acid (trans) Maleic acid (cis)  ISOMERISM Stereoisomers Compounds with the same molecular formula, functional groups, and position of functional groups but with different conformations optical isomers with different conformation around chiral or asymmetric carbon atoms The carbon C is asymmetric if A, B, D, and E B are four different groups A C D The four different groups A, B, D, and E can be arranged in space around the C-atom in two different ways to generate two different E compounds  ISOMERISM Stereoisomers Compounds with the same molecular formula, functional groups, and position of functional groups but with different conformations optical isomers with different conformation around chiral or asymmetric carbon atoms The mirror images can’t be superimposed on each other, B B i.e. they are different A C D D C A The mirror image isomers constitute an enantiomeric pair; one member of the pair is said E E to be the enantiomer of the other Mirror  ISOMERISM B B A C D D C A E E Mirror One member of an enantiomeric pair will rotate a plane of polarized light in a clockwise direction. It is said to be dextrorotatory which is labelled (+) The other member of the pair will then rotate the light in a counterclockwise direction. It is said to be levorotatory which is labelled (-) Reference compound for optical isomers is the simplest monosaccharide with an asymmetric carbon: glyceraldehyde O H C C-atom 1 C-atom 2 H- C - OH C-atom 3 CH2OH O H O H C C CH2OH H- C - OH HO- C - H C O CH2OH CH2OH CH2OH D-Glyceraldehyde L-Glyceraldehyde Dihydroxyacetone D-Glyceraldehyde is assigned to be the isomer that has the hydroxyl group on the right when the aldehyde group is at the top in a Fischer projection formula. It is also dextrorotatory, so it is also D(+)-Glyceraldehyde  If a compound has n asymmetric carbon atoms then there are 2n different optical isomers Number of Number of Number of carbon atoms Aldose/Ketose asymmetric carbon atoms optical isomers 3 Aldose 1 2 4 Aldose 2 4 5 Aldose 3 8 6 Aldose 4 16 3 Ketose 0 - 4 Ketose 1 2 5 Ketose 2 4 6 Ketose 3 8 D & L designate absolute configuration of the asymmetric carbon atom farthest from the aldehyde or ketone group CHO CHO CHO CHO Ι Ι Ι Ι H – C – OH OH – C – H OH – C – H H – C – OH Ι Ι Ι Ι H – C - OH OH – C - H H – C - OH OH – C - H Ι Ι Ι Ι CH2OH CH2OH CH2OH CH2OH D-Erythrose L-Erythrose D-Threose L-Threose Optical isomers that are not enantiomers are diastereomers Diastereomers that differ by their configuration on a single asymmetric carbon are epimers CHO CHO CHO CH2OH Ι Ι Ι Ι H – C – OH HO – C – H H – C – OH C=O CHO Ι Ι Ι Ι Ι HO – C – H HO – C – H HO – C – H HO – C – H HO – C – OH Ι Ι Ι Ι Ι H – C – OH H – C – OH HO – C – H H – C – OH H – C – OH Ι Ι Ι Ι Ι H – C – OH H – C – OH H – C – OH H – C – OH H – C – OH Ι Ι Ι Ι Ι CH2OH CH2OH CH2OH CH2OH CH2OH D-Glucose D-Mannose D-Galactose D-Fructose D-Ribose C6H12O6 C6H12O6 C6H12O6 C6H12O6 C5H10O5 Reactions involving aldehyde and keto groups in carbohydrates Aldehyde + Alcohol Hemiacetal Ketone + Alcohol Hemiketal With ring formation involving the aldehyde- or ketone-carbon atom, this carbon atom also becomes asymmetric, giving two possible isomers called anomers The carbon atom is the anomeric carbon The hydroxyl group bound to the anomeric carbon is the anomeric hydroxyl group. In Haworth formulas of D-pentoses and D-hexoses, the α-anomer has the anomeric hydroxyl written below the ring plane the β-anomer has the anomeric hydroxyl written above the ring plane 6-membered ring: Pyranose 5-membered ring: Furanose Mutarotation: Spontaneous conversion of one anomer to the other CH2OH CH2OH H O H O H OH H H OH H OH H OH OH OH H CHO H OH Ι H OH H – C – OH α-anomer Ι β-anomer HO – C – H Ι H – C – OH Ι H – C – OH Ι CH2OH D-Glucose  Learn (know) these structures CH2OH CH2OH CH2OH H O OH H O OH OH O OH H H H OH H OH OH OH H OH H OH H H H H OH H H H OH D-Glucopyranose D-Mannopyranose D-Galactopyranose CH2OH CH2OH CH2OH OH O O H OH H H H OH H H OH H OH OH D-Fructofuranose D-Ribofuranose Glycosidic bonds Formation: A glycosidic bond forms through a condensation reaction occurs between the anomeric carbon of one sugar molecule and the hydroxyl group (-OH) of another molecule.  Glycosidic bonds Types of Glycosidic Bonds: O-glycosidic bond: most common type and involves the oxygen atom linking the sugar's anomeric carbon to another molecule's hydroxyl group. N-glycosidic bond: involves a N atom, often linking the anomeric carbon of a sugar to an amine group S-glycosidic bond: Less common, this bond involves a sulfur atom instead of oxygen. C-glycosidic bond- anomeric carbon is directly linked to a carbon atom of another molecule  Dietary carbohydrates Starch Sucrose Digestible Glucose and fructose Lactose Cellulose Other plant polysaccharides Non-digestible by humans Only monosaccharides are absorbed into the bloodstream from the gut. Digestion of carbohydrates involves their hydrolysis into monosaccharides  Digestive Enzymes Enzymes for carbohydrate digestion Enzyme Source Substrate Products α-Amylase Salivary gland Starch, glycogen Oligosaccharides Pancreas Dextrinase Small intestine Oligosaccharides Glucose Isomaltase Small intestine α-1,6-glucosides Glucose Maltase Small intestine Maltose Glucose Lactase Small intestine Lactose Galactose, glucose Sucrase Small intestine Sucrose Fructose, glucose Lactase deficiency produces lactose intolerance  Absorption of monosaccharides by intestinal mucosal cells Major monosaccharides Glucose, galactose, fructose Entry into mucosal cells from intestinal lumen Active transport of glucose and galactose with a concurrent uptake of Na+ ions (SGLT-1) Facilitated transport of fructose via transporter protein GLUT-5 Entry into the portal circulation from mucosal cells Facilitated transport via transporter protein GLUT-2 Absorption of monosaccharides by intestinal mucosal cells  Blood glucose concentrations Measured in mmol/L = mM or in mg/dL Conversion factor: 1 mM = 18 mg/dL Normal plasma glucose concentrations roughly 3.9 – 8.3 mM Hypoglycemia: < 2.2 mM Diabetes: > 7.0 mM (fasting) > 11.1 mM 2 h after ingestion of 75 g glucose All cells can use glucose as an energy source Brain cells and erythrocytes require glucose as an energy source