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

    open access unreviewed
  2. 2
    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

    open access unreviewed
  3. 3
    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

    open access unreviewed
  4. 4
    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
  5. 5
    Effects of HFPO-DA (GenX) exposure on placental glycolysis and metabolic microenvironment in pregnant rats.

    Pang Y, Wang Z, Liu Y, Feng C, Song Y, Cao S, Wang D, Zhang L, Lu P, Yu L. · 2026-06-23

    unreviewed
  6. 6
    The role of cuproptosis in osteoporosis: Molecular mechanisms and cell-specific regulation in bone metabolic imbalance.

    He J, Li F, Yuan H, Liu J, Peng Y, Wu H, Luo Y, Li F, Xu W, Song C, Hao P, Liu Z. · 2026-05-21

    unreviewed
  7. 7
    Next generation AAV-F capsid gene therapy rescues disease pathology in a model of pyruvate dehydrogenase complex deficiency.

    Keegan A, Çetin Ö, Chilcott EM, Diaz JA, Eaton S, Waddington SN, Counsell JR, Rahman S, Karda R. · 2026-06-15

    unreviewed
  8. 8
    From inactivation to intervention: X chromosome silencing in disease pathogenesis and emerging therapeutic strategies.

    Fu Y, Tan X, Qin L, Wang C. · 2025-12-05

    open access unreviewed
  9. 9
    Ultra-early post-mortem interval (PMI) estimation based on longitudinal plasma protein dynamics in humans: A pilot study.

    Sacco MA, Malara N, Presta I, Turturiello R, Garofalo E, Bruni A, Aquila I. · 2026-05-18

    unreviewed
  10. 10
    Targeting melanocortin-4 receptor (MC4R) family in goldfish (Carassius auratus) for enhanced growth and optimized lipid distribution.

    Mo H, Lv B, Liu Y, Yu H, Du Y, Wang X, Gao J, Yao M, Zhang Q, Yu J, Li Y, Wang L. · 2026-05-07

    unreviewed

External claims. These come from an index outside this database and are not checked against it. Treat them as leads.