6 - Tricarboxylic Acid Cycle (Kreb Cycle)

where does pyruvate oxidation and citric acid cycle occur?

matrix of mitochondria

what are different ways that acetyl-CoA is formed?

1. pyruvate from glycolysis
2. B-oxidation of FA
3. amino acid catabolism produce pyruvate or acetyl-CoA

what enzyme is used for the conversion of pyruvate to acetyl-CoA?

pyruvate dehydrogenase complex

what are each subunit of pyruvate dehydrogenase ? and what are the cofactors?

E1 = pyruvate dehydrogenase → TPP

E2 = dihydroliposmide transacetylase → lipoic acid, Coenzyme A

E3 = dihydrolipoamide dehydrogenase → flavin adenine dinucleotide (FAD), Nicotinamide adenine dinucleotide (NAD+)

what is the purpose of riboflavin ?

phosphorylation of riboflavin forms flavin mononucleotide (FMN) which is then used as a electron acceptor on the E3 of pyruvate dehydrogenase

how is the E1 subunit regulated ?

activated = PDH phosphatase (dephosphorylation)

inhibited = PDH kinase (phosphorylation)

how is the E1 pyruvate dehydrogenase regulated?

activated = PDH phosphatase

inhibited = PDH kinase

how is PDH kinase regulated?

activate = ATP, NADH, Acetyl-CoA

inhibit = Pyruvate, ADP

how is PDH phosphatase regulated ?

activate = Mg2+, Ca2+, and insulin

what are the general reactions in the TCA cycle?

1. condensation
2. done to citrate → isocitrate


1. dehydration
2. hydration
3. oxidative decarboxylation
4. oxidative decarboxylation
5. substrate-level phosphorylation
6. dehydrogenation
7. hydration
8. dehydrogenation

what is produced for each acetyl-CoA?

1 GTP (S5)

3 NADH (S3, S4, S8)

1 FADH2 (S6)

2 CO2

what are the irreversible steps of the TCA cycle?

S1: condensation (acetyl-CoA + oxaloacetate → citrate)

S3: decarboxylation (isocitrate → a-ketoglutarate)

S4: oxidative decarboxylation (a-ketoglutarate → succinyl-CoA)

what is an important characteristic of succinate dehydrogenase ?

located in inner mitochondrial membrane

belongs to complex II of respiratory chain

why is step 8 of the TCA cycle despite have a negative free energy?

low concentration of reactants

* more oxaloacetate is converted back to L-malate
* to be used in gluconeogenesis

how is citrate synthase regulated?

inhibited = NADH, succinyl-CoA

how is isocitrate dehydrogenase regulated?

activated = ADP, Ca2+

inhibited = NADH, ATP

how is a-ketoglutarate dehydrogenase regulated?

activated = Ca2+

inhibited = NADH, succinyl-CoA

citrate is a allosteric inhibitor of what? why?

PFK

* high conc increase inhibitory effect of ATP

what are anaplerotic and cataplerotic reactions ?

anaplerotic = rxn replenish intermediates of TCA cycle

cataplerotic = rxn that use TCA intermediates to make others

how many ATP is produced as a result of NADH and FADH2

NADH = 2.5ATP

FADH2 = 1.5 ATP

how many ATP is produced in each step up till the electron transfer phosphorylation?

glycolysis = 2 ATP

TCA cycle = 2 ATP

electron transfer phosphorylation = 28 ATP

how many reducing power is converted using the glycerol-3-phosphate pathway or the malate-asparate shuttle?

G3P shuttle → 2 NADH = 2 NADH

malate-aspartate shuttle → 2 NADH = 2 FADH2