1. O2O2 O2O2 O2O2 O2O2 O2O2 O2O2 O2O2 O2O2 METABOLISM OF PYRUVATE METABOLISM OF PYRUVATE Its time to get aerobic

2. COO C=O CH 3  ketoacid Carboxyl group (acid) Ketone group (carbonyl) Methyl group Pyruvate Structure – 2 -2 + 2 CH 3 C-OHC=O O –2 C O O Net = – 2 Oxidation of Carbon +2 Look for one NAD + for each glyceraldehyde-3-PO 4 oxidized to pyruvate -OH 0 0 H-C-OH CHO CH 2 OH P Glyceraldehyde 3-Phosphate

3. Reactions of Pyruvate Each is catalyzed by a specific enzyme: (2) Add CO 2 (3) Reduce to alcohol (Lactate) (1) Pyruvate decarboxylase (anaerobic -yeast) (1) Pyruvate dehydrogenase (aerobic-mitochondria) (2) Pyruvate carboxylase (mitochondria) (3) Lactate dehydrogenase (anaerobic-cytosol) (1) Decarboxylate as CO 2 H 3 C-C-COO - O Remove as CO 2

4. Decarboxylation Reactions Two Types: non-oxidative and oxidative No change in oxidation state of carbonyl C H 3 C-C:COO - O H 3 C-C+ O NAD + NADH H 3 C-C: O CO 2 Oxidized carbonyl C Oxidative Non-oxidative H 3 C-C:H O H+H+ H 3 C-C-OH O H2OH2O

5. The Energy Story of Glycolysis Overall ANAEROBIC (no O 2 ) Glucose + 2ADP + 2P i 2 Lactate + 2ATP + 2H 2 O Glucose + 2ADP + 2P i 2 Ethanol + 2CO 2 +2ATP + 2H 2 O Overall AEROBIC Yeast Glucose + 2ADP + 2P i + 2NAD + 2 Pyruvate + 2ATP + 2NADH + 2H + + 2H 2 O 6 ATPs

6. C 6 H 12 O 6 + 6O 2 6CO 2 + 6H 2 O CHO CH 2 OH H-C-OH OH-C-H H-C-OH D-Glucose  G o’ = -2,840 kJ/mol  G o’ = -146 kJ/mol C 6 H 12 O 6 2 C 3 H 4 O 3 Glucose2 Pyruvate COO - C=O CH 3 COO - C=O CH 3 5.2% Energy used 146 2,840 100 = Anaerobic Aerobic 2 Pyruvates

7. Glycolysis Oxidative phosphorylation pyruvate Krebs Cycle 3 NADH Glucose Galactose Fructose Mannose Fatty Acids 1 FADH 2 Lactate Amino Acids O2O2 H2OH2O Anaerobic Aerobic Acetyl-Coenzyme A Pyruvate dehydrogenase Complex Pyruvate dehydrogenase Dihydrolipoyl transacetylase Dihydrolipoyl dehydrogenase NAD Coenzyme A Lipoic acid Thiamin pyrophosphate FAD

8. Thiamin pyrophosphate CH 3 COOC O Pyruvate + Carbanion Vitamin B-1 : + CO 2

9. Pantothenate CH 3 C O Acetyl Group Thioester bond COENZYME A Acetyl-Coenzyme A B-vitamin HS-CH 2 -CH 2 -N H -P-O-P-O OO O O -C-C-C-CH 2 -O OH HOCH 3 H -C-CH 2 -CH 2 -N O Adenosine-3’- phosphate Textbook p369

10. Dihydrolipoate CHCH 2 SH HS COO 6,8 Dithiooctonoate (Reduced, gained 2 electrons) SS CH 2 CHCH 2 COO (Oxidized, lost 2 electrons) Long hydrocarbon chain Disulfide bond

11. E3E3 Pyruvate Dehydrogenase Complex FAD TPP S S E1E1 E2E2 Pyruvate Dehydrogenase Dihydrolipoyl Transacetylase Dihydrolipoyl dehydrogenase H H.. CH 3 -C OH S S C-CH 3 O.. H2H2 Acetyl-CoA HS-CoA NAD + NADH.. CH 3 -C O Textbook p471-475

12. What about Yeast Rule: Yeast do not synthesize lactate. Instead they make acetaldehyde to regenerate NAD + from NADH. Rule: Acetaldehyde comes from pyruvate via a non-oxidative decarboxylation. CH 3 -C-COO O CH 3 -C O : O : H CH 3 -C-H O CO 2 CH 3 CH 2 OH Leavens bread Makes wine sparkle Leavens bread Makes wine sparkle Levels people Makes AA sparkle Levels people Makes AA sparkle NADHNAD + Alcohol dehydrogenase Pyruvate decarboxylase pyruvate acetaldehyde ethanol