ALLOSTERIC ENZYMES

Pyruvate Dehydrogenase Complex

Catalyses the conversion of pyruvate to acetyl-CoA

Regulates TCA cycle

via: product inhibition and reversible phosphorylation

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Pyruvate Dehydrogenase Complex - inhibitors

acetyl-CoA

NADH

E1

Pyruvate dehydrogenase

E2

Dihydrolipoyl transacetylase

E3

Dihydrolipoyl dehydrogenase

co-enzymes

FAD: Flavin Adenine Dinucleotide

CoA-SH: Co-enzyme A

NAD+: Nicotine Adenin Dinucleotide

TPP: Thiamine Pyrophosphate

Lipoate

Enzymatic events: step 1

* E1 has pyruvate binding site
* decarboxylation of pyruvate
* hydroxyethyl derivative formed
* TPP co-enzyme is then bound to it on E1
* product: CO2

Enzymatic events: step 2

* hydroxyethyl group is oxidised on E2
* forms acetate group
* acetyl group is transfered to one of the lipoyl-SH
* transesterification of CoA to form acetyl CoA and fully reduced form of lipoyl group

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Enzymatic events: step 3

* transfer of 2 hydrogen atoms from reduced lipoyl groups of E2 to the FAD of E3
* by dihydrolipoyl dehydrogenase
* results in regeneration of oxidised form of lipol-lysyl group of E2
* transfer of proton from FADH2 to NAD → NADH2

Allosteric control of PDC

binding of end products, NADH and Acetyl-CoA - inhibits PDC activation

high prdocuts conc. = inactive PDC

binding of substrates, pyruvate and ADP to PDC - promotes PDC activity

more subrates available = more active PDC

covalent mo