Pyruvate dehydrogenase E1
Cofactors used
Clinical / pharmacological. PDC deficiency (X-linked): lactic acidosis, neurological disease; thiamine-responsive forms
What it does, reaction by reaction
Pyruvate Oxidation / Link Reaction (Pyruvate Dehydrogenase Complex) Carbohydrate Metabolism · Mitochondrial matrix
Pyruvate + thiamine pyrophosphate (TPP) → hydroxyethyl-TPP + CO2
Converts Pyruvate Thiamine pyrophosphate (TPP) into Hydroxyethyl-TPP CO2
› Notes
The E1 component, pyruvate dehydrogenase (pyruvate decarboxylase), requires tightly bound TPP and Mg2+. It decarboxylates pyruvate and retains the two-carbon hydroxyethyl group on TPP; this is the decarboxylation portion of the overall irreversible reaction.
Hydroxyethyl-TPP + oxidized lipoamide (E2) → acetyl-lipoamide + TPP
Converts Hydroxyethyl-TPP Oxidized lipoamide into Acetyl-lipoamide Thiamine pyrophosphate (TPP)
› Notes
E1 transfers and oxidizes the hydroxyethyl group to the lipoyllysine swinging arm of E2, dihydrolipoyl transacetylase. Lipoic acid/lipoamide serves as the redox-active prosthetic group.
Pyruvate Dehydrogenase Complex (Link Reaction, connecting glycolysis to the TCA cycle) Energy Metabolism & Cellular Respiration · Mitochondrial matrix
Pyruvate + TPP → hydroxyethyl-TPP + CO2
Converts Pyruvate Thiamine pyrophosphate (TPP) into Hydroxyethyl-TPP CO2
› Notes
Required coenzyme: thiamine pyrophosphate (TPP), derived from vitamin B1, and Mg2+ for TPP binding. This is the first irreversible chemical event in the overall reaction; release of CO2 helps make PDC flux effectively irreversible in vivo.
Showing all 3 reactions.
What accelerates and inhibits it
Regulation is pathway-specific, so each context is listed separately
Pyruvate Dehydrogenase Complex (Link Reaction, connecting glycolysis to the TCA cycle)
Listed there as: Pyruvate dehydrogenase complex (active when dephosphorylated)
ADP, pyruvate, CoA-SH, NAD+, Ca2+ in contracting muscle; PDH phosphatase
ATP, NADH, acetyl-CoA; PDH kinase phosphorylation
Insulin activates PDH phosphatase in adipose tissue and promotes PDH activity for lipogenesis; epinephrine-associated Ca2+ signaling and muscle contraction promote phosphatase activity
Pyruvate Dehydrogenase Complex (Link Reaction, connecting glycolysis to the TCA cycle)
Listed there as: Pyruvate dehydrogenase kinase (PDK)
ATP, NADH, acetyl-CoA; prolonged fasting and high fatty-acid oxidation increase PDK expression/activity
ADP, pyruvate, CoA-SH; dichloroacetate
Insulin tends to suppress PDK expression; glucagon/fasting favor PDK-mediated PDH inhibition in liver
Pyruvate Dehydrogenase Complex (Link Reaction, connecting glycolysis to the TCA cycle)
Listed there as: Pyruvate dehydrogenase phosphatase (PDP)
Ca2+; Mg2+; insulin in insulin-responsive tissues
Indirectly opposed by conditions favoring PDK
Insulin stimulates PDP, particularly in adipose tissue; Ca2+ activates PDP in skeletal and cardiac muscle
Pyruvate Oxidation / Link Reaction (Pyruvate Dehydrogenase Complex)
Listed there as: Pyruvate dehydrogenase E1 (active when dephosphorylated)
ADP, pyruvate, CoA-SH, NAD+; Ca2+ in contracting muscle promotes dephosphorylation
ATP, NADH, acetyl-CoA; phosphorylation by pyruvate dehydrogenase kinase
Insulin activates pyruvate dehydrogenase phosphatase in adipose tissue and liver; epinephrine/Ca2+ stimulate phosphatase in muscle
Pyruvate Oxidation / Link Reaction (Pyruvate Dehydrogenase Complex)
Listed there as: Pyruvate dehydrogenase kinase
ATP, NADH, acetyl-CoA
ADP, pyruvate, CoA-SH, dichloroacetate
Induced by fasting/high-fat states; insulin opposes the fasting program
Pyruvate Oxidation / Link Reaction (Pyruvate Dehydrogenase Complex)
Listed there as: Pyruvate dehydrogenase phosphatase
Ca2+, Mg2+; insulin in adipose and liver
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Insulin promotes dephosphorylation/activation of PDC; Ca2+ couples muscle contraction to PDC activation
Recent literature
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