1 Chem 30B Handout: Metabolism Catabolism Flow Chart

Chem 30B Handout: Metabolism

Catabolism Flow Chart

FOOD

Fatty Acids + Glycerols Glucose + Amino Acids Other Sugars Pentose Phosphate Amino Acid Fatty Acids Pathway Glycogenesis Catabolism 5-C sugars Glycogen + NAPDH Glucose 6-phosphate β-oxidation Glycolysis 2 NADH + 2 ATP

*Glycolysis yields 2 pyruvates, so multiply everything below by 2x! O O Anaerobic - H3C C C O Lactate n NADH Pyruvate Aerobic + n FADH2 (n depends on carbon CO2 NADH length of fatty acid) O Steroids H3C C SCoA Ketone Protein bodies Acetyl-CoA metabolism

Citric Acid Cycle 1 ATP 2 CO2

3 NADH, 1 FADH2

O2 Electron Transport Chain & Oxidative H2O Phosphorylation

11 ATP (3 ATP/NADH + 2 ATP/FADH2) 1 H. Kim for Chem 30B

2 H. Kim for Chem 30B

Glucose and Fatty Acid Catabolism

I. Glucose Catabolism

A. Steps of Glucose Catabolism

1. Glycolysis: glucose + 2 NAD+ + 2 HOPO32- + 2 ADP à 2 pyruvate + 2 NADH + 2 ATP + 2 H2O + 2 H+

2. Pyruvate Oxidation: 2 pyruvate + 2 NAD+ + 2 HSCoA à 2 Acetyl-CoA + 2 CO2 + 2 NADH + 2 H+

3. Citric Acid Cycle: 2 Acetyl-CoA + 6 NAD+ + 2 FAD + 2 ADP + 2 HOPO32- + 4 H2O à 2 HSCoA + 6 NADH + 6 H+ + 2 FADH2 + 2 ATP + 4 CO2

4. Electron Transport/Oxidative Phosphorylation: Electrons from all the NADH and FADH2 made in the previous steps are used to reduce O2 to water: O2 + 4e- + 4 H+ à 2 H2O

The released energy is used to make ATP: 3 ATP made/1 NADH 2 ATP made/1 FADH2 (More accurate: 2.5 ATP/NADH, 1.5 ATP/ FADH2)

B. Total ATP Count for Catabolism of a Glucose Molecule

• Glycolysis: 2 ATP + 6 ATP (from 2 NADH) = 8 ATP • Pyruvate oxidation: 6 ATP (from 2 NADH) = 6 ATP • Citric Acid Cycle: 2 ATP + 18 ATP (from 6 NADH) + 4 ATP (from 2 FADH2) = 24 ATP ______TOTAL: 38 ATP

3 H. Kim for Chem 30B II. Fatty Acid Catabolism

A. Steps of Fatty Acid Catabolism

1. Activation of fatty acid: O O O O – – R C O– + HSCoA + ATP R C SCoA + AMP + O P O P O Fatty acid O– O– Fatty acyl-CoA

2. Trans-membrane transport of fatty acyl-CoA from cytosol into mitochondrial matrix

3. β-Oxidation of fatty acyl-CoA (Repeat for each 2-carbon unit EXCEPT for the last 2-carbon unit, since the last β-oxidation cleaves 4-carbon chain to give two acetyl-CoA molecules):

For each round of β-oxidation

Fatty acyl-CoA + FAD + H2O + NAD+ + HSCoA à Fatty acyl-CoA shorted by 2 carbons + FADH2 + NADH/H+ + Acetyl-CoA

4. Citric Acid Cycle: Acetyl-CoA + 3 NAD+ + FAD + ADP + HOPO32- + 2 H2O à HSCoA + ATP + 2 CO2 + 3 H+ +3 NADH + FADH2

5. Electron Transport/Oxidative Phosphorylation: 3 ATP made/1 NADH, and 2 ATP made/1 FADH2

B. Total ATP Count for Catabolism of a Fatty Acid Molecule

• Activation: –2 ATP [One-time loss for the whole fatty acid molecule]

• β-Oxidation: 2 ATP (per FADH2) + 3 ATP (per NADH) = 5 ATP/ β-oxidation round

! !"# x No. of β-oxidation rounds = No. of ATP from all β-oxidation rounds ! !!!"#$%&#!' !"#$%

!".!" !"#$%& !"#$% !" !"##$ !"#$ *Note: No. of β-oxidation rounds = − 1 !

• Citric acid cycle: No. of carbon atoms in fatty acid/2 = No. of acetyl-CoA

!" !"# x No. of acetyl-CoA = No. of ATP from all acetyl-CoA ! !"#$%&!!"# ______

TOTAL: Net ATP from three steps above. 4 H. Kim for Chem 30B Three Metabolic Pathways

I. Glycolysis

HO CH 2- 2 Hexokinase O3PO CH2 Fructose 6-phosphate kinase O OH OH Glucose 6-phosphate ATP ADP O OH isomerase 2-O PO CH ATP ADP 3 2 O OH H H OH H OH 1 OH H OH H 3 2 H CH2OH H OH OH H OH H Glucose Glucose 6-phosphate Fructose 6-phophate

O H2 2- O3PO C C CH2OH Dihydroxyacetone phosphate 2- OH O3PO CH2 O Aldolase H OH Triose phosphate 5 isomerase H 2- CH2OPO3 4 Glyceraldehyde 3-phosphate OH H dehydrogenase O OH O Fructose 1,6-bisphosphate OH H2 H2 NAD+ NADH/H+ HOPO 2- 2- 3 2-O PO C C C OPO 2- O3PO C C CH 3 3 H H D-Glyceraldehyde 6 1,3-Bisphosphoglycerate 3-phosphate

Phosphoglycerate kinase H2O OPO 2– Enolase OPO 2– ADP ATP Phosphoglycerate mutase 3 3 OH O O H2 H O 2- – 2 – O3PO C C C O HO C C C O– H2C C C O H 9 7 8 H 3-Phosphoglycerate 2-Phosphoglycerate Phosphoenolpyruvate

Pyruvate kinase ADP ATP O O – H3C C C O Pyruvate 10

II. β-Oxidation of Fatty Acid

H O OH O H H O FAD FADH2 O 2 R CH2CH2 C C C SCoA R CH2CH2 C C C SCoA R CH2CH2 C C C SCoA H H H H H H 2 Acyl-CoA dehydrogenase Enoyl-CoA hydratase Fatty acyl-CoA 1 2

+ + H–SCoA O NAD NADH/H O O O C SCoA R CH2CH2 C SCoA + H3C R CH2CH2 C C C SCoA β-Hydroxyacyl-CoA dehydrogenase H2 Acyl-CoA acetyltransferase 3 4 Further rounds of β-oxidation

5 H. Kim for Chem 30B

III. Citric Acid Cycle

O H–SCoA COO COO H3C C SCoA NAD+ CH2 + CH2 NADH/H HC COO H2O HO C COO CO2 Aconitase HO CH Isocitrate CH2 COO COO synthase 2 COO dehydrogenase Citrate COO CH2 C O 1 Isocitrate Citrate 3 CH2 CH 2 C O COO COO Oxaloacetate α-Ketoglutarate

H-SCoA + NADH/H + Malate NAD 8 α- dehydrogenase 4 NAD+ + Ketoglutarate NADH/H dehydrogenase

CO2

COO HO CH COO 7 CH CH2 5 2 GDP CH COO H2O 6 GTP 2 HSCoA C O Malate COO FADH FAD COO 2 SCoA Fumerase CH CH 2 CoA Succinyl-CoA CH CH2 Succinyl COO Succinate synthetase dehydrogenase COO Fumarate Succinate

6 H. Kim for Chem 30B