Citric acid cycle

Question 1

PDH

Answer 1

Pyruvate dehydrogenase

Pyruvate + NAD+ + CoA -> AcetylCoA + NADH + CO2

Inside mitochondria (pyruvate channels)
Irreversible

Huge complex - 3 enzymes
Pyr -> Ac-TPP -> Ac-lipoic acid -> AcCoA
Co-factors and regulation separate slides

Question 2

Electron carriers

Answer 2

Electron carrier systems (travel with H)

NAD+ (ox) –reduced–> NADH (red)
NADPH (red)
(usu used for reduction, gets oxidized)

FAD (ox) FADH2 (red)

Question 3

PDH co-factors

Answer 3

Niacin (B3) = NAD+ (electron carrier)
Thiamine (B1) = TPP (transfers acetyl group)
Riboflavin (B2) = FAD (electron carrier)
Panothenic acid (B5) = CoA (accepts acetyl group)

Question 4

PDH regulation

Answer 4

Phosphorylation = inactive

(+) ADP, NAD+ -> activate phosphatase
(+) pyruvate, ADP -> inhibit kinase
(-) ATP, AcCoA, NADH -> activate kinase

Question 5

Ethanol metabolism

Answer 5

Alcohol dehydrog (cytoplasm) -> acetaldehyde
Aldehyde dehydrog (matrix) -> acetate
Thiokinase -> AcCoA

First 2 steps require NAD+
 (depletes cell and can cause hypoglycemia)
Step 3 requires ATP
Unregulated pathway to AcCoA (vs PDH)
 (can cause overall metabolic problems)

Question 6

Isocitrate dehydrogenase

Answer 6

Isocitrate + NAD -> Ketoglutarate + NADH

Major regulation of citric acid cycle
 (ATP vs fatty acid synthesis via citrate)
Irreversible
(+) ADP, NAD
(-) ATP, NADH

Question 7

Electron transport chain

Answer 7

Electron carriers linked to H+ pumps
-> gradient across inner membrane -> ATPase

Complex I = NADH oxidase -> ubiquinol ->
Complex III -> Cytochrome c -> IV -> O2

Succinate -> fumarate

• enzyme = complex II (part of CAC and ETC)
• > direct to complex III

Question 8

Anapleurotic reactions

Answer 8

Replacement of citric acid cycle intermediates
(only needed if they have been used for synthesis of fatty acids, amino acids, purines, pyrimadines, porphyrins…)

Pyruvate (via carboxylase)
Glutamate
(Ac-CoA does not count! Needs to add onto an oxaloacetate)

Question 9

Uncoupling

Answer 9

Diffusion of H+ across mitochondrial membrane without ATP synthesis
 ex DNP (weight loss drug, athletes)

-> Heat (brown fat, thermogenesis, fever)
-> Low ATP (no gradient)
-> High throughput of glycolysis, CAC, ETC
(low ATP:ADP)
-> acidosis (CO2 and compensatory lactic acidosis)

Question 10

Citric acid cycle overview

Answer 10

Multiple sites of entry, multiple products
In mitochondrion

Ac-CoA (provides 2C) -> 2 CO2
 (intermediates conserved)
3 NAD -> 3 NADH
FAD -> FADH2
GDP -> GTP (only direct energy)

Major regulation = IDH

Question 11

Citric acid cycle products

Answer 11

Citrate -> fatty acids and sterols
Ketoglutarate -> amino acids, purines
Succinyl CoA -> porphyrins
Oxaloacetate -> amino acids, purines, pyrimadines