 2009 Cengage-Wadsworth Chapter 3 Carbohydrates

 2009 Cengage-Wadsworth Structural Features Simple carbohydrates –Monosaccharides –Disaccharides Complex carbohydrates –Oligosaccharides –Polysaccharides

 2009 Cengage-Wadsworth Simple Carbohydrates Monosaccharides –Steroisomerism Chiral carbon - have 4 different atoms or groups attached to them Stereoisomers - have 2 or more chiral carbon atoms with same 4 groups attached but are not mirror images of each other

 2009 Cengage-Wadsworth Simple Carbohydrates –Ring structures - molecules cyclize & form another chiral carbon –Haworth models –Pentoses –Reducing sugars

 2009 Cengage-Wadsworth Simple Carbohydrates Disaccharides –Maltose –Lactose –Sucrose

 2009 Cengage-Wadsworth Complex Carbohydrates Oligosaccharides –Raffinose –Stachyoses –Verbascose Polysaccharides –Starch –Glycogen –Cellulose

 2009 Cengage-Wadsworth Digestion Polysaccharides –Salivary -amylase - mouth –Pacreatic -amylase - small intestine –Resistant starches Digestion of disaccharides –Disaccharidases - active in microvilli of enterocytes

 2009 Cengage-Wadsworth Absorption, Transport, & Distribution Absorption of glucose & galactose –Into cell: active transport - SGLT1 –Into blood: diffusion, GLUT2 Absorption of fructose –Into cell: facilitated transport - GLUT5 –Into blood: GLUT2 –Limited in 60% of adults

 2009 Cengage-Wadsworth Absorption, Transport, & Distribution Monosaccharide transport & cellular uptake Glucose transporters –GLUT isoforms Integral proteins Each has specific combining site Undergoes a conformational change upon binding the molecule Can reverse this change when unbound

 2009 Cengage-Wadsworth Absorption, Transport, & Distribution –Specificity of GLUTs GLUT1 - basic supply of glucose to cells GLUT2 - low infinity transporter; glucose from enterocyte to blood GLUT3 - high-affinity for brain & other glucose-dependent tissues GLUT4 - insulin sensitive, in muscle & adipose tissues GLUT5 - for fructose

 2009 Cengage-Wadsworth Absorption, Transport, & Distribution Insulin –Role in cellular glucose absorption Binds to membrane receptor Stimulates GLUT4 to move to membrane Maintenance of blood glucose levels

 2009 Cengage-Wadsworth Glycemic Response to Carbohydrates Glycemic index –Increase in blood glucose during 2- hour period after consumption of a certain amount of CHO compared with equal CHO from reference food Glycemic load –GI x g of CHO in 1 serving of food

 2009 Cengage-Wadsworth Integrated Metabolism in Tissues Glycogenesis –Conversion of glucose to glycogen Glycogenolysis –Breakdown of glycogen to glucose –Phosphorolysis process –Regulation of phosphorylase Covalent - glucagon, epinephrine Allosteric - AMP

 2009 Cengage-Wadsworth Integrated Metabolism in Tissues Glycolysis - degradation of glucose to pyruvate –Hexokinase/glucokinase reaction –Glucose phosphate isomerase –Phosphofructokinase reaction –Aldolase reaction –Glyceraldehyde 3-phosphate & dihydroxyacetone phosphate

 2009 Cengage-Wadsworth Integrated Metabolism in Tissues –Oxidation of glyceraldehyde 3-phosphate to carboxylic acid, incorporation of inorganic phosphate into high-energy anhydride bond –Substrate-level phosphorylation of ADP –Phosphoglyceromutase –Dehydration of 2-phosphoglycerate –Phophoenolpyruvate (PEP) donates phosphate group to ADP –Lacate dehydrogenase reaction

 2009 Cengage-Wadsworth Integrated Metabolism in Tissues –Fructose enters pathway –Galactose is phophorylated –Galactose 1-phosphate converted to glucose 1-phosphate –Glucose 6-phosphate enters hexosemonophophate shunt –Glucose 1-phosphate enteres glycogenesis –Glucose can enter glycolysis

 2009 Cengage-Wadsworth Integrated Metabolism in Tissues Substrate-level phosphorylation The tricarboxylic acid cycle –TCA pathway Formation of citrate from oxaloacetate & acetyl CoA Isomerization of citrate to isocitrate Dehydrogenation catalyzed by isocitrate dehydrogenase Decarboxylation & dehydrogenation of - ketoglutarate

 2009 Cengage-Wadsworth Integrated Metabolism in Tissues Hydrolysis of thioester bond of acetyl CoA drives phosphorylation of guanosine diphosphate (GDP) Succinate dehydrogenase reaction Fumerase incorporates H 2 O across double bond of fumarate to form malate Malate converted to oxaloacetate –ATPs produced by complete glucose oxidation C 6 H 12 O 6 + 6O 2  6CO 2 + 6H 2 O + energy Yields 12 ATPs + 2 mol acetyl CoA per 1 mol glucose = 24 ATPs

 2009 Cengage-Wadsworth Integrated Metabolism in Tissues –Acetyl CoA oxidation and tricarboxylic acid cycle intermediates –NADH in anaerobic & aerobic glycolysis: the shuttle systems Glycerol 3-phosphate shuttle system Malate-aspartate shuttle system

 2009 Cengage-Wadsworth Integrated Metabolism in Tissues Formation of ATP –Biological oxidation & the electron transport chain Electron transport chain = sequential reduction-oxidation Oxidative phosphorylation = oxidation of a metabolite by O 2 through electron transport + phosphorylation of ADP

 2009 Cengage-Wadsworth Integrated Metabolism in Tissues –Anatomical site for oxidative phosphorylation –Components of the oxidative phosphorylation chain Complex I NADH-coenzyme Q oxidoreductase Complex II Complex III coenzyme Q-cytochrome c oxidoreductase Complex IV

 2009 Cengage-Wadsworth Integrated Metabolism in Tissues –Phosphorylation of ADP to form ATP –Translocation of H + –ATP synthase

 2009 Cengage-Wadsworth Integrated Metabolism in Tissues The hexosemonophosphate shunt (pentose phosphate pathway) –Pentose phosphates –Reduced cosubstrate NADPH Gluconeogenesis –Synthesis of glucose from non-CHO –Reversal of glycolytic pathway –Lactate utilization –Efficient glycogenesis

 2009 Cengage-Wadsworth Regulation of Metabolism 4 mechanisms: –Negative or positive modulation of allosteric enzymes –Hormonal activation by covalent modification/induction –Directional shifts in reactions –Translocation of enzymes within cells

 2009 Cengage-Wadsworth Regulation of Metabolism Allosteric enzyme modulation –AMP, ADP, & ATP as allosteric modulators –AMP’s positive modulation Causes shift from inactive to active form of phosphorylase b Stimulates phosphofructokinase

 2009 Cengage-Wadsworth Regulation of Metabolism Regulatory effect of NADH:NAD + ratio Hormonal regulation –Glycolytic enzymes –Bifunctional enzymes –Gluconeogenic enzymes Directional shifts in reversible reactions

 2009 Cengage-Wadsworth Perspective 3 Hypoglycemia: Fact or Fall Guy?

 2009 Cengage-Wadsworth Hypoglycemia Preprandial vs. postprandial serum glucose levels Types: –Fasting hypoglycemia Usually caused by insulin, sulfonylureas –Fed (reactive) hypoglycemia Impaired glucose tolerance, idiopathic postprandial syndrome