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Pyruvate synthase

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pyruvate synthase
Identifiers
EC no.1.2.7.1
CAS no.9082-51-3
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
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In enzymology, a pyruvate synthase (EC 1.2.7.1) is an enzyme that catalyzes the interconversion of pyruvate and acetyl-CoA. It is also called pyruvate:ferredoxin oxidoreductase (PFOR).

The relevant equilibrium catalysed by PFOR is:

pyruvate + CoA + oxidized ferredoxin acetyl-CoA + CO2 + reduced ferredoxin + 2 H+

The 3 substrates of this enzyme are pyruvate, CoA, and oxidized ferredoxin, whereas its 4 products are acetyl-CoA, CO2, reduced ferredoxin, and H+.

Function

This enzyme participates in 4 metabolic pathways: pyruvate metabolism, propanoate metabolism, butanoate metabolism, and reductive carboxylate cycle (CO2 fixation).

Its major role is the extraction of reducing equivalents by the decarboxylation. In aerobic organisms, this conversion is catalysed by pyruvate dehydrogenase, also uses thiamine pyrophosphate but relies on lipoate as the electron acceptor. Unlike the aerobic enzyme complex PFOR transfers reducing equivalents to flavins or iron-sulflur clusters. This process links glycolysis to the Wood–Ljungdahl pathway.

Nomenclature

This enzyme belongs to the family of oxidoreductases, specifically those acting on the aldehyde or oxo group of donor with an iron-sulfur protein as acceptor. The systematic name of this enzyme class is pyruvate:ferredoxin 2-oxidoreductase (CoA-acetylating). Other names in common use include:

  • pyruvate oxidoreductase,
  • pyruvate synthetase,
  • pyruvate:ferredoxin oxidoreductase, and
  • pyruvic-ferredoxin oxidoreductase.

Inhibitors

Amixicile is a potent inhibitor of pyruvate ferredoxin oxidoreductase and is in pre-clinical studies to treat infections of Helicobacter pylori and Clostridium difficile.[1]

Nitazoxanide is an FDA-approved PFOR inhibitor which is used for the treatment of Giardia and Cryptosporidium.

References

  1. ^ Warren CA, van Opstal E, Ballard TE, Kennedy A, Wang X, Riggins M, Olekhnovich I, Warthan M, Kolling GL, Guerrant RL, Macdonald TL, Hoffman PS (August 2012). "Amixicile, a novel inhibitor of pyruvate: ferredoxin oxidoreductase, shows efficacy against Clostridium difficile in a mouse infection model". Antimicrob. Agents Chemother. 56 (8): 4103–11. doi:10.1128/AAC.00360-12. PMC 3421617. PMID 22585229.{{cite journal}}: CS1 maint: multiple names: authors list (link)

Further reading