21-1 Principles and Applications of Inorganic, Organic, and BiologicalChemistry Denniston, Topping, and Caret 4 th ed Chapter 21 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Power Point to Accompany

21-2 Introduction Major pathways of carbohydrate metabolism. Fig rd ed

ATP: Cellular Energy Currency Complete combustion of a mole of glucose yields 686 kcal. Adenosine triphosphate (ATP) serves as a “go-between” molecule that couples exergonic catabolism reactions to endergonic anabolic reactions. ATP “captures “ energy as phosphoanhydride bonds. Phosphoester bond Phosphoanhydride bonds Hydrolysis of the anhydride bonds provides energy for anabolism.

21-4 ATP Example ATP + H 2 O  ADP + P i + 7 kcal/mol 3.0 kcal/mol + glucose + P i  glucose-6-phosphate + H 2 O Net ___________________________________ Glucose + ATP  glucose-6-phosphate + ADP + 4 kcal/mol

Catabolism Insert Fig 21.4 DTC

21-6 Catabolism-cont. Stage 1: Hydrolysis to Small Subunits Food molecules are degraded: Polysaccharides Begins in the mouth with amylase action on starch. Continues in small intestine (SI) to form monosaccharides. Proteins Begins in the stomach. In SI to amino acids. Fats Begins in SI. To fatty acids and glycerol.

21-7 Catabolism-cont. Stage 2: Conversion of monomers to a form that can be completely oxidized. Sugars: glycolysis and TCA cycle Fatty acids: enter TCA cycle as acetyl CoA Stage 3: Complete Oxidation/ATP produced. Acetyl CoA enters the TCA cycle and electrons and hydrogen atoms are harvested as CO2 is produced.

Glycolysis (Embden-Meyerhof Pathway) The anerobic oxidation of glucose (G) to give two molecules of pyruvate. G + 2 ADP + 2 P i + 2 NAD +  2 pyruvate +2 ATP + 2 NADH + 2 H H 2 O Products: Substrate-level phosphorylation gives 4 ATP A phosphoryl group is transferred to ADP! from 1,3-bisphosphoglycerate and phosphoenolpyruvate. NADH carries hydride anions with two electrons. Pyruvate: fate depends on cellular conditions.

21-9 Glycolysis: Step 1, 2 hexokinase glucose + ATP fructose-6- phosphate + ADP glucose-6-phosphate phosphoglucose isomerase

21-10 Glycolysis: Step 3 (Committed Step) + ATP fructose-1,6-bisphosphate + ADP phosphofructokinase Two molecules of ATP have now been used.

21-11 Glycolysis: Step 4, 5 dihydroxyacetone phosphate D-glyceraldehyde-3-phosphate aldolase triosephosphate isomerase

21-12 Glycolysis: Step 6 + NAD + + HPO 4 2- Glycerate-1,3-bisphosphate + NADH + H + glyceraldehyde 3-phosphate dehydrogenase Phosphorylation and a two electron oxidation by NAD + occur.

21-13 Glycolysis: Step 7, 8 + ADP 3-phosphoglycerate + ATP phospho- glycerate kinase phosphoglycerate mutase 2-phospho glycerate

21-14 Glycolysis: Step 9, 10 Phosphoenolpyruvate (PEP) + H 2 O enolase “High energy bond” + ATP pyruvate kinase

21-15 Regulation of Glycolysis EnzymeActivatorInhibitor Hexokinase (Step 1) Glucose-6- Phosphate, ATP PFK (Step 3) Fructose-2,6-bis phosphate, AMP Citrate, ATP Pyruvate kinase (Step 10) Fructose-1,6-bis phosphate, AMP Acetyl-CoA, ATP All the above enzymes are allosteric.

Fermentation + NADH + H + lactate dehydrogenase lactate + NAD + This reaction produces NAD + which is needed for further anerobic glycolysis. Glyceraldehyde 3-phosphate --> glycerate-1,3-bisphosphate

21-17 Fermentation, cont, pyruvate decarboxylase ethanol + NAD + NADH + H +

Pentose Phosphate Pathway The PP Pathway is an alternative to glycolysis. In stage 1, the oxidative stage, NADPH for biosynthesis is produced. In stage 2, three ribulose-5-phosphate result. In stage 3, ribose-5-phosphate and two xylulose-5-phosphate are produced along with two fructose-6-P and glyceraldehyde-3- P. The nonoxidative stages (2, 3) produce sugars with from 3 to 7 carbons. The ribose sugar is critical for nucleic acid synthesis.

Gluconeogenesis Gluconeogenesis makes glucose from noncarbohydrate (lactate, glycerol, and most AA) starting materials primarily in the liver. The three nonreversable steps of glycolysis must be bypassed with new routes. Pyruvate  PEP Fructose-1,6-bisP  furctose-6-P Glucose-6-P  glucose

21-20 Pyruvate to PEP + ATP + CO 2 + H 2 O pyruvate carboxylase oxaloacetate + ADP + P i + H + Phosphoenol- pyruvate carboxykinase GTP CO 2 + GDP +

21-21 F-1,6-bP  F-6-P and G-6-P  Glucose fructose-1,6- bisphosphatase glucose-6- phosphatase

21-22 Gluconeogenesis Substrates Step 3 glycolysis: phosphofructokinase Stimulated by: high AMP, ADP, P i Inhibited by: high ATP Reverse gluconeogenesis: fructose-1,6-bisphosphatase Stimulated by: high ATP In the Cori cycle, lactate from skeletal muscle is transferred to the liver where it is converted to pyruvate then glucose which can be returned to the muscle.

Glycogen Glucose is the sole source of energy for mammalian red blood cells and the major source for the brain. It is supplied in the diet, via glycogenolysis, or by gluconeogenesis. Glycogen (Ch 17) is a highly branched  (1  4) and  (1  6) polymer of glucose. It exists as granules found in the cytoplasm of liver and muscle cells.

21-24 Glycogenolysis Glycogen degradation) is controlled by glucagon (pancreas) and epinephrine (adrenal gland). The pancreas responds to low blood sugar and the adrenal gland to stress/threat. Step 1: Glycogen phosphorylase catalyzes removal of an end glucose as glucose-1-P. Step 2: Debranching enzyme catalyzes removal of the last glucose at an  (1  6) branch as glucose. Step 3: Phosphoglucomutase converts glucose-1-P to glucose-6-P.

21-25 Glycogenesis Insulin (pancreas) stimulates synthesis of glycogen. glucose + ATP  glucose-6-P + ADP + H + Enzyme: glucokinase glucose-6-P  glucose-1-P Enzyme: phosphoglucomutase Now the glucose must be activated to add to the growing glycogen chain. G-1-P + UTP  UDP-glucose + PP i (see next slide) UDP-glucose adds to the growing glycogen.

21-26 Glycogenesis-2 Pyrophosphate hydrolyzes UDP glucose- phosphorylase UDPG

21-27 Glycogenesis-3 Glycogen synthase A new  -1,4 bond is formed

21-28 Glycogenesis vs Glycogenolysis High blood sugar (hyperglycemia) Insulin: stimulates glucose uptake elevates glucokinase activates glycogen synthetase inhibits glycogen phosphorylase Low blood sugar (hypoglycemia) Glucagon: stimulates glycogen phosphorylase Inhibits glycogen synthetase Thus glycogen synthesis and degradation do not compete.

21-29 The End Carbohydrate Metabolism