TCA Regulation

Right side TCA cycle

Exergonic and react in clockwise direction

Left side TCA Cycle

Reversible and will depend much more on the relative concentrations of the metabolites

enzymes are regulated…

Far from equilibrium

Primary regulators of the TCA cycle

1) substrates or products, e.g. acetyl-CoA, oxaloacetate, NADH

2) Energy charge (ATP vs. ADP)

Mechanism of regulation

1) Concentration of reactants of products

2) Allosteric regulation

3) phosphorylation

Regulation of the Pyruvate Dehydrogenase Complex by feedback inhibition

Exergonic, so this step can be regulated

Unless the products are being removed continuously:

E2– competitive inhibition by the concentration acetyl-CoA

E3 – competitive inhibition by NADH

Covalent modification of PDH Complex regulation

E1 is regulated by phosphorylation in mammals

Energy poor Pyruvate dehydrogenase phosphatase active = PDH active

Energy rich Pyruvate dehydrogenase kinase active = PDH inactive

How many pyruvate dehydrogenase kinase isozymes?

4

How many pyruvate dehydrogenase phosphatase isozymes?

2

What determines activity of PDH?

Isozymes and ratio of kinase and phosphatase in different tissues determines the activity of PDH

Primary mechanism of regulation of PDH:

Covalent modification of PDH Complex

Most important regulator of TCA cycle:

ratio of [NAD+]/[NADH]