Re-characterisation of Saccharomyces cerevisiae Ach1p: fungal CoA-transferases are involved in acetic acid detoxification

Fungal Genet Biol. 2009 Jun-Jul;46(6-7):473-85. doi: 10.1016/j.fgb.2009.03.004. Epub 2009 Mar 17.

Abstract

Saccharomyces cerevisiae and Neurospora crassa mutants defective in the so-called acetyl-CoA hydrolases Ach1p and Acu-8, respectively, display a severe growth defect on acetate, which is most strongly pronounced under acidic conditions. Acetyl-CoA hydrolysis is an energy wasting process and therefore denoted as a biochemical conundrum. Acetyl-CoA hydrolases show high sequence identity to the CoA-transferase CoaT from Aspergillus nidulans. Therefore, we extensively re-characterised the yeast enzyme. Ach1p showed highest specific activity for the CoASH transfer from succinyl-CoA to acetate and only a minor acetyl-CoA-hydrolase activity. Complementation of an ach1 mutant with the coaT gene reversed the growth defect on acetate confirming the in vivo function of Ach1p as a CoA-transferase. Our results imply that Ach1p is involved in mitochondrial acetate detoxification by a CoASH transfer from succinyl-CoA to acetate. Thereby, Ach1p does not perform the energy wasting hydrolysis of acetyl-CoA but conserves energy by the detoxification of mitochondrial acetate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetic Acid / metabolism*
  • Acetyl Coenzyme A / metabolism
  • Acetyl-CoA Hydrolase / chemistry*
  • Acetyl-CoA Hydrolase / genetics
  • Acetyl-CoA Hydrolase / isolation & purification
  • Acetyl-CoA Hydrolase / metabolism
  • Kinetics
  • Mitochondria / chemistry
  • Mitochondria / enzymology
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / isolation & purification
  • Saccharomyces cerevisiae Proteins / metabolism
  • Substrate Specificity

Substances

  • Saccharomyces cerevisiae Proteins
  • Acetyl Coenzyme A
  • Acetyl-CoA Hydrolase
  • Acetic Acid