Reversible heme-dependent regulation of human cystathionine β-synthase by a flavoprotein oxidoreductase

Biochemistry. 2011 Oct 4;50(39):8261-3. doi: 10.1021/bi201270q. Epub 2011 Sep 6.

Abstract

Human CBS is a PLP-dependent enzyme that clears homocysteine, gates the flow of sulfur into glutathione, and contributes to the biogenesis of H(2)S. The presence of a heme cofactor in CBS is enigmatic, and its conversion from the ferric- to ferrous-CO state inhibits enzyme activity. The low heme redox potential (-350 mV) has raised questions about the feasibility of the ferrous-CO state forming under physiological conditions. Herein, we provide the first evidence of reversible inhibition of CBS by CO in the presence of a human flavoprotein and NADPH. These data provide a mechanism for cross talk between two gas-signaling systems, CO and H(2)S, via heme-mediated allosteric regulation of CBS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Carbon Monoxide / metabolism*
  • Cystathionine beta-Synthase / antagonists & inhibitors
  • Cystathionine beta-Synthase / metabolism*
  • Ferric Compounds / metabolism
  • Ferrous Compounds / metabolism
  • Flavoproteins
  • Heme / metabolism*
  • Humans
  • Hydrogen Sulfide / metabolism*
  • Oxidation-Reduction
  • Oxidoreductases / metabolism*

Substances

  • Ferric Compounds
  • Ferrous Compounds
  • Flavoproteins
  • Heme
  • Carbon Monoxide
  • Oxidoreductases
  • Cystathionine beta-Synthase
  • Hydrogen Sulfide