Development of a satisfactory and general continuous assay for aminotransferases by coupling with (R)-2-hydroxyglutarate dehydrogenase

Anal Biochem. 2012 Dec 15;431(2):127-31. doi: 10.1016/j.ab.2012.09.009. Epub 2012 Sep 19.

Abstract

A continuous general spectrophotometric assay for measuring the activity of aminotransferases has been developed. It is based on the transamination of a keto compound (amino acceptor) and l-glutamate (amino donor), yielding the corresponding amino compound and 2-oxoglutarate. The rate of formation of 2-oxoglutarate is measured in a coupled reaction with overproduced recombinant nicotinamide adenine dinucleotide (NAD(+))-dependent (R)-2-hydroxyglutarate dehydrogenase from Acidaminococcus fermentans, with the rate of absorbance decrease at 340nm indirectly reflecting the aminotransferase activity. This new method allows continuous monitoring of the course of transamination. Because glutamate and 2-oxoglutarate are obligatory participants in most biological transamination reactions, a coupled assay based on measuring the formation of 2-oxoglutarate has very wide applicability. The article demonstrates its utility with branched-chain amino acid aminotransferase and l-valine:pyruvate aminotransferase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidaminococcus / enzymology
  • Alcohol Oxidoreductases / chemistry*
  • Glutamic Acid / chemistry
  • Humans
  • Ketoglutaric Acids / chemistry
  • NAD / chemistry
  • Spectrophotometry / methods*
  • Transaminases* / chemistry
  • Transaminases* / isolation & purification

Substances

  • Ketoglutaric Acids
  • NAD
  • Glutamic Acid
  • Alcohol Oxidoreductases
  • 2-hydroxyglutarate dehydrogenase
  • Transaminases