Pyruvate synthase

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 $\rightleftharpoons$ 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

• Nitazoxanide is a broad-spectrum antiparasitic drug and FDA-approved PFOR inhibitor which is used for the treatment of Giardiasis and Cryptosporidiosis.
• Tizoxanide, an active metabolite of nitazoxanide
• Amixicile, a water-soluble derivative of nitazoxanide, is a potent inhibitor of pyruvate:ferredoxin oxidoreductase and is in pre-clinical studies to treat infections of Helicobacter pylori and Clostridium difficile.