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unreviewed

Pyruvate dehydrogenase E1

3 reactions · 2 pathways

Cofactors used

TPP (B1) · B1 (Thiamine) Mg2+ · Magnesium Lipoamide

Clinical / pharmacological. PDC deficiency (X-linked): lactic acidosis, neurological disease; thiamine-responsive forms

What it does, reaction by reaction

3 reactions

Pyruvate Oxidation / Link Reaction (Pyruvate Dehydrogenase Complex) Carbohydrate Metabolism · Mitochondrial matrix

step 1 Irreversible

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.

step 2 Irreversible/directional

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

step 1 Irreversible

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

6 entries

Pyruvate Dehydrogenase Complex (Link Reaction, connecting glycolysis to the TCA cycle)

Listed there as: Pyruvate dehydrogenase complex (active when dephosphorylated)

Accelerated by

ADP, pyruvate, CoA-SH, NAD+, Ca2+ in contracting muscle; PDH phosphatase

Inhibited by

ATP, NADH, acetyl-CoA; PDH kinase phosphorylation

Hormonal control

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)

Accelerated by

ATP, NADH, acetyl-CoA; prolonged fasting and high fatty-acid oxidation increase PDK expression/activity

Inhibited by

ADP, pyruvate, CoA-SH; dichloroacetate

Hormonal control

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)

Accelerated by

Ca2+; Mg2+; insulin in insulin-responsive tissues

Inhibited by

Indirectly opposed by conditions favoring PDK

Hormonal control

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)

Accelerated by

ADP, pyruvate, CoA-SH, NAD+; Ca2+ in contracting muscle promotes dephosphorylation

Inhibited by

ATP, NADH, acetyl-CoA; phosphorylation by pyruvate dehydrogenase kinase

Hormonal control

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

Accelerated by

ATP, NADH, acetyl-CoA

Inhibited by

ADP, pyruvate, CoA-SH, dichloroacetate

Hormonal control

Induced by fasting/high-fat states; insulin opposes the fasting program

Pyruvate Oxidation / Link Reaction (Pyruvate Dehydrogenase Complex)

Listed there as: Pyruvate dehydrogenase phosphatase

Accelerated by

Ca2+, Mg2+; insulin in adipose and liver

Inhibited by

—

Hormonal control

Insulin promotes dephosphorylation/activation of PDC; Ca2+ couples muscle contraction to PDC activation

Recent literature

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Europe PMC · fetched just now · sorted by publication date

  1. 1
    Metabolic engineering of <i>Escherichia coli</i> based on adaptive evolution and omics technology for highly efficient l-valine production under oxygen-limited conditions.

    Zhang H, Ha Z, Wei A, Zhao C, Meng G, Li X, Wu F, Liu J, Wu H, Ma Q, Xie X. · 2026-06-18

    open access unreviewed
  2. 2
    Hepatocyte SLC31A1-dependent copper accumulation contributes to hepatic glucose and lipid metabolic disturbances through AMPKα1 inactivation.

    Cheng YQ, Wei M, Yang L, Zhuang YY, Lu QB. · 2026-09-11

    open access unreviewed
  3. 3
    Suppression of LncRNA AC008406.3 sensitizes breast cancer cells to docetaxel via triggering cuproptosis.

    Liu C, Liu S, Lu Z, Cao X, Tong X, Sun I, Hao J, Zhang L. · 2026-05-26

    open access unreviewed
  4. 4
    Metabolic memory in the kidney: how lactate and lactylation drive the path from acute injury to chronic disease.

    Zhang X, Dai Q, Feng H. · 2026-05-20

    cited 1× open access unreviewed
  5. 5
    A review of the sirtuins family: pivotal regulators and emerging therapeutic targets in renal fibrosis.

    Deng Q, Li C, Luo J, Yin M, Qian S, Li L. · 2026-05-14

    cited 1× open access unreviewed
  6. 6
    LncRNA UNC5C-AS1 inhibits angiogenesis and induces endothelial apoptosis via the miR-148a-3p/EMP1 axis in preeclampsia.

    Wang Y, Gao Y, Liu L, Ma K, He Y, Qi H, Zhang X. · 2026-02-06

    open access unreviewed
  7. 7
    Consensus Guidelines for Diagnosis and Management of Pyruvate Dehydrogenase Complex Deficiency.

    Keshavan N, Neugebauer J, Bellusci M, Bertini E, Brown G, Darin N, DeBrosse S, Drexler L, Drexler S, Enns GM,… · 2026-11-01

    cited 1× open access unreviewed
  8. 8
    Essential Oral Single Nutritional Therapy Products for Inherited Metabolic Diseases: Evidence and Consensus Assessment Using a Modified Delphi Method.

    Stolwijk NN, Penninx BMF, Bosch AM, Langeveld M, Salomons GS, Hollak CEM, Essential Nutritional Therapy Produ… · 2026-11-01

    open access unreviewed
  9. 9
    Reprogramming of cell death in gastric cancer: From molecular mechanisms to therapeutic potential (Review).

    Liu M, Wu Z, Chen Q, Ni W, Chen Y, Zhu Y, Chen Y, Ma H, Lin Y. · 2026-09-25

    open access unreviewed
  10. 10
    Research progress on lysine acetylation (Review).

    Zhang M, Zhang Y, Yin H, Yan J, Dong Y, Zhao X, Cui T, Lv B, Gao X. · 2026-09-04

    open access unreviewed

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