Lecture 10: Citric Acid Cycle

Citric acid cycle

Topic 10

1. pyruvate 3-carbon molecule that can be oxidized further ultimately to 3 CO₂ molecules
2. pyruvate made in cytosol
3. pyruvate further oxidized in mitochondria
4. some intermediates glycolysis and CAC are used in to synthesize amino acids and other essential molecules
5. precursors for synthesis
6. amino acids when degraded can be used as intermediates of CAC
7. 1 g protein = 1g carbon ⟶ for ATP production

The Mitochondria

1. two membranes
2. outer membrane relatively large pore that allow molecules (even polar/charged) up to 5000Da cross freely
3. inner membrane doesn't have same pores, impermeable to small polar molecules
4. need some type of transporter
5. cristae (folds inner membrane) that increased surface area
6. very important because a lot of rxns occurs there
7. intermembrane space extends to folds of cristae
8. matrix - space enclosed by inner membrane

Coenzyme A

1. A - stands for adenosine
2. nucleotide
3. shuttles around molecules
4. commonly fatty acids
5. acetyl-coa
6. two phosphate attach pantothenic acid residue
7. derived from vitamin B₅
8. Left most molecule - SH thiol
9. can add other molecules to thiol group in thio-ester linkage
10. when broken, releases energy
11. group added is activated form

Cellular Respiration

1. process by which the three carbons in pyruvate are oxidized to CO₂
2. electrons from that process end up being added to molecular oxygen to make H₂0
3. electron transport processes allow phosphate to be added to ADP to make ATP
4. breathing provides oxygen required and takes away CO₂ produced

Oxidation Pyruvate

1. conversion of 3 carbon pyruvate to acetyl CoA and CO₂
2. Acetyl CoA further oxidized in citric acid cycle
3. (both produce NADH)

Decarboxylation of Pyruvate

Net Rxn:

Pyruvate + CoA + NAD⁺

↓

Acetyl - CoA + CO₂ + NADH

1. one of 3 carbons on pyruvate fully oxidized to CO₂ and electrons transferred to NAD⁺ ⟶ NADH
2. remaining 2 carbons added to make acetyl CoA
3. process catalyzed by large multi subunit complex called pyruvate dehydrogenase
4. 60 protein subunits and multiple enzyme activities
5. important because cell is committing carb ⟶ lipid

Regulation of Pyruvate Dehydrogenase

1. which form dominates in cell regulated by insulin and conditions

1. acetyl CoA and NADH also competitive inhibitors of enzyme

Citric Acid Cycle

1. dependent on O₂ accept e^- from NADH or rxn stops because no NAD+
2. oxidation two acetyl carbons to CO₂ in CA cycle
3. many steps CA cycle near equilibrium
4. 3 steps are irreversible
5. no alternate rxn exist that can do reverse rxn
6. concludes that CA cycle irreversible
7. Unidirectional

Net Rxn of CA Cycle

Aceytl-CoA + 3NAD⁺ + Q + GDP + P_i

↓

2CO₂ + CoA + 3NADH + QH₂ + GTP

2CO₂ ⟶ waste

CoA ⟶ recycled

3NADH and QH₂ ⟶ Electron Transport - must regenerate NAD⁺ and Q

GTP ⟶ ATP ⟶ useable energy

Regulation CAC

1. Availability of substrates
2. Competitive Inhibition Products
3. Allosteric Regulations