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Section 6 5. Pentose phosphate pathway Krebs cycle Carbohydrate catabolism: control, dental aspects 10/28/05.

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Presentation on theme: "Section 6 5. Pentose phosphate pathway Krebs cycle Carbohydrate catabolism: control, dental aspects 10/28/05."— Presentation transcript:

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2 Section 6 5. Pentose phosphate pathway Krebs cycle Carbohydrate catabolism: control, dental aspects 10/28/05

3 Pentose phosphate pathway  alternate catabolism of glucose 6-P  energy channeled into reducing potential (high-energy e – s), not ATP  cytosol of most cells, especially adipose tissue, liver  functions: synthesis of pentoses, supply e – s for fat synthesis  coenzyme: NADP  NAD with a phosphoryl group on a 2' ribose  e – carrier used in reductive biosynthesis (e.g., fatty acid synthesis)  stoichiometry varies with specific cell, situation  stoichiometry of version that maximizes making NADPH: glc 6-P + 12 NADP H 2 O → 6 CO NADPH + 12 H + + P i 1

4 Pentose phosphate pathway: first 2 steps, control  Control of the pentose phosphate pathway: glc 6-P DHase rate controlled by [NADP + ] 6-P gluconate DHase  ribose-P, other sugars 2

5 Overview of catabolism adapted from Fig FATSPOLYSACCHARIDESPROTEINS fatty acids, glycerol glucose, other sugars amino acids acetyl CoA Krebs cycle e – CO 2 oxidative phosphorylation CoA ATP ADP + P i H 2 O O 2 Stage 3 Stage 1 Stage 2 v v pyruvate

6 The Krebs Cycle  aka the citric acid cycle; the tricarboxylic acid (TCA) cycle; the final common pathway for fuel oxidation  location: mitochondrial matrix  function: acetyl group → 2 CO 2 ATP production  aerobic O 2 not used directly O 2 not used directly  NADH & FADH 2 transfer e – pairs to e – transport chain  transfer required to regenerate e – carriers  ATP made by oxidative phosphorylation 3

7 The Krebs Cycle (steps 1-4) step enzyme reaction type 1 citrate synthase* condensation (Claisen) 1 citrate synthase* condensation (Claisen) 2,3aconitase isomerization via dehydration-hydration 4 isocitrate DHase † oxidative decarboxylation 4 isocitrate DHase † oxidative decarboxylation *inh by ATP † inh by NADH, ATP; activ by ADP 4

8 The Krebs Cycle (steps 5-9) step enzymereaction type 5  -ketoglutarate DHaseoxid. decarb. 5  -ketoglutarate DHaseoxid. decarb. 6succinyl thiokinasephosphorylation driven by thioester hydrolysis 7succinate DHaseoxid.-reduction (complex II) 6succinyl thiokinasephosphorylation driven by thioester hydrolysis 7succinate DHaseoxid.-reduction (complex II) 8fumarasehydration 8fumarasehydration 9malate DHaseoxid.-reduction 9malate DHaseoxid.-reduction 5

9 Connection to electron transport chain  most e – s enter e – chain via NADH  transferred from NADH via 3 complexes (I, III, IV) to O 2  end up in H 2 O via transfer to O 2 (the final electron acceptor) stoichiometry: NADH + H + + ½ O 2 → NAD + + H 2 O (2.5 ATP made)  some e – s enter via FADH 2 enzymes (enter e – chain at Q) stoichiometry: FADH 2 + ½ O 2 → FAD + H 2 O (1.5 ATP made) NADH →complx I →Q → complx III → cyt c → complx IV NADH → complx I → Q → complx III → cyt c → complx IV from ↑  ↓ from ↑  ↓ mal-asp shuttle FADH 2 enzymes:  O 2 pyr DHase succinate DHase (complex II) Krebs cycle DHases GOP DHase hydroxyacyl CoA DHase* acyl CoA DHase* others others * fatty acid catabolism (Section 7) Lehninger 3ed Fig

10 Stoichiometries ATP ATP Krebs cycle (steps 1-9): yield 2FAD + 6NAD + + 2acetyl CoA + 6H 2 O → 2FADH 2 + 6NADH + 6H + + 2CoA + 4CO 2 2 oxidative phosphorylation: 2FADH 2 + 6NADH + 6H + + 4O 2 → 2FAD + 6NAD + + 8H 2 O 18 stage III: 2acetyl CoA + 4O 2 → 4CO 2 + 2H 2 O + 2CoA 20 add in stages I & II: glucose + 2O 2 + 2CoA → 2acetyl CoA + 2CO 2 + 4H 2 O complete oxidation of glc: glucose + 6 O 2 → 6 CO H 2 O glucose + 6 O 2 → 6 CO H 2 O

11 Replenishing (anaplerotic) reactions  cycle intermediates used to make other biomolecules  e.g., succinyl CoA → hemeoxaloacetate → aspartate  cycle itself results in no net change of [intermediates] (slide 7: Stage III)  other reactions needed to ↑ [intermediates]  example of a replenishing reaction: CH 3 COCOO – + HCO 3 – → – OOCCH 2 COCOO – pyruvate oxaloacetate  driven by being coupled to ATP hydrolysis  enzyme: pyruvate carboxylase (coenzyme: biotin)  allosterically activated by acetyl CoA  same reaction as gluconeogenesis: step 10'a (S6L4,slide4) 8

12 Krebs cycle: anaerobic conditions  Krebs cycle is the same in microorganisms as in eukaryotes  cycle is aerobic (linked to electron transport chain)  to regenerate e – carriers (e.g., NAD + ), e – transfer to O 2 must occur  under anaerobic conditions, some microorganisms produce acids from cycle “backup”  examples: acetyl CoA + ADP + Pi → ATP + acetic acid + CoA succinate → CO 2 + propionic acid (CH 3 CH 2 COOH)  these acid products are membrane-permeant  by acidifying local regions, products can damage tissues e.g., in caries & periodontal disease, they are among the numerous substances that cause damage 9

13 Control of metabolic pathways  feedback inhibition usually an early step (committed step) of a pathway is inhibited by a pathway product  example: a pathway functioning to produce F: A → B → C → D → E → F F will often allosterically inhibit step A → B or B → C  in catabolism, main product is ATP, so ATP common allosteric inhibitor  feedforward activation usually a precursor: of the pathway’s product or of a related pathway’s product  example: AMP & ADP as precursors of ATP 10

14 Control of carbohydrate catabolism glycogen AMP, ADP  AMP, ADP  glucose 6-P fructose 6-P AMP, ADP   AMP, ADP   fructose 1,6 bisP pyruvate AMP   AMP    acetylCoA  acetylCoA oxaloacetatecitrate isocitrate ADP    -ketoglutarateATP NADH ↑ ox phos ADP + P i ADP + P i  GLYCOLYSIS KREBS CYCLE GLYCOGEN- OLYSIS   × pentoseP ? pathway 11

15 Dental aspects of carb metabolism: summary  sucrose  source of fermentable monosaccharides  an activated precursor of plaque polysaccharides  plaque polysaccharides (mutans, dextrans, levans)  synthesis catalyzed by bacteria-secreted sucrases  adhesion, fuel, anaerobic conditions for microorganisms  anaerobic conditions (fermentation)  glycolysis lactic acid  Krebs cycle acetic acid, propionic acid, others  low pH  solubilizes enamel hydroxyapatite (caries)  damages supporting tissue proteins, cells (gingivitis, periodontal disease, pulpitis) 12

16 Web links  Stryer site: Chapter 19 (Glycolysis) Stryer site: Chapter 19 (Glycolysis) Stryer site: Chapter 19 (Glycolysis)  see also Chapters 18, 20, 22 at that site  Carbohydrate Structure and Metabolism from the University of Kansas Medical Biochemistry Center. This site is essentially an online course in carbohydrates and many biochemical pathways. Carbohydrate Structure and Metabolism Carbohydrate Structure and Metabolism

17 Next section: 7. Lipid Metabolism Next exam (#6): Monday, Nov. 7 at 8 a.m.


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