Comparative studies of Acyl-CoA dehydrogenases for monomethyl branched chain substrates in amino acid metabolism

Bioorg Chem. 2013 Apr:47:1-8. doi: 10.1016/j.bioorg.2012.12.001. Epub 2012 Dec 29.

Abstract

Short/branched chain acyl-CoA dehydrogenase (SBCAD), isovaleryl-CoA dehydrogenase (IVD), and isobutyryl-CoA dehydrogenase (IBD) are involved in metabolism of isoleucine, leucine, and valine, respectively. These three enzymes all belong to acyl-CoA dehydrogenase (ACD) family, and catalyze the dehydrogenation of monomethyl branched-chain fatty acid (mmBCFA) thioester derivatives. In the present work, the catalytic properties of rat SBCAD, IVD, and IBD, including their substrate specificity, isomerase activity, and enzyme inhibition, were comparatively studied. Our results indicated that SBCAD has its catalytic properties relatively similar to those of straight-chain acyl-CoA dehydrogenases in terms of their isomerase activity and enzyme inhibition, while IVD and IBD are different. IVD has relatively broader substrate specificity than those of the other two enzymes in accommodating various substrate analogs. The present study increased our understanding for the metabolism of monomethyl branched-chain fatty acids (mmBCFAs) and branched-chain amino acids (BCAAs), which should also be useful for selective control of a particular reaction through the design of specific inhibitors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl-CoA Dehydrogenase / metabolism*
  • Amino Acid Sequence
  • Amino Acids, Branched-Chain / chemistry
  • Amino Acids, Branched-Chain / genetics
  • Amino Acids, Branched-Chain / metabolism*
  • Animals
  • Fatty Acids / metabolism
  • Isovaleryl-CoA Dehydrogenase / chemistry
  • Isovaleryl-CoA Dehydrogenase / genetics
  • Isovaleryl-CoA Dehydrogenase / metabolism*
  • Kinetics
  • Liver / enzymology
  • Molecular Sequence Data
  • Mutation
  • Oxidoreductases Acting on CH-CH Group Donors / chemistry
  • Oxidoreductases Acting on CH-CH Group Donors / genetics
  • Oxidoreductases Acting on CH-CH Group Donors / metabolism*
  • Rats
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Sequence Alignment
  • Substrate Specificity

Substances

  • Amino Acids, Branched-Chain
  • Fatty Acids
  • Recombinant Proteins
  • Oxidoreductases Acting on CH-CH Group Donors
  • Isovaleryl-CoA Dehydrogenase
  • Acyl-CoA Dehydrogenase
  • 2-methylacyl-CoA dehydrogenase