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Pyruvate Dehydrogenase Complex function
catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA
location of the pyruvate dehydrogenase complex
mitochondrial matrix
what needs to happen to pyruvate for oxidative decarboxylation to happen
it must cross both mitochondrial membranes
oxidative decarboxylation of pyruvate reaction
pyruvate + CoA + NAD+ ——> Acetyl-CoA + CO2 + NADH
oxidative decarboxylation of pyruvate reaction ΔG°'
-33.4 kJ/mol so irreversible
Pyruvate dehydrogenase complex
a massive multienzyme complex with three enzymes
What are the three enzymes that compose the pyruvate dehydrogenase complex
Pyruvate dehydrogenase (TPP cofactor)
Dihydrolipoyl transacetylase (Lipoate, CoA)
Dihydrolipoyl dehydrogenase (FAD, NAD+)
What are the five coenzymes required for the oxidative decarboxylation of pyruvate
TPP - thiamine pyrophosphate
Lipo - lipoate
FAD - flavin adenine
CoA - coenzyme A
NAD - nicotinamide adenine dinucleotide
pyruvate dehydrogenase complex mechanism step 1
Decarboxylation (E1 + TPP)
pyruvate binds to TPP
CO2 released
Hydroxyethyl-TPP formed
pyruvate dehydrogenase complex mechanism step 2
Oxidation (E1 → E2)
hydrozyethyl group transferred to lipate
oxidized to acetyl group
lipoate reduced to dihydrolipoate
pyruvate dehydrogenase complex mechanism step 3
Transfer to CoA (E2)
acetyl group transferred to CoA
Acetyl-CoA released
pyruvate dehydrogenase complex mechanism step 4-5
Regeneration (E3)
dihydrolipoate oxidized by FAD
FADH2 oxidized by NAD+
NAD+ → NADH
Why is the pyruvate dehydrogenase complex highly regulated
because it controls entry into the TCA cycle
Allosteric regulation of pyruvate dehydrogenase complex: inhibitors
Acetyl-CoA
NADH
ATP
Allosteric regulation of pyruvate dehydrogenase complex: activators
CoA
NAD+
ADP
PDH kinase
phosphorylates E1 → inactivates PDC
PDH phosphatase
dephosphorylates E1 → activates PDC
Insulin
activates phosphatase → PDC on
Glucagon
activates kinase → PDC off