Human liver long-chain 3-hydroxyacyl-coenzyme a dehydrogenase is a multifunctional membrane-bound beta-oxidation enzyme of mitochondria

doi:10.1016/0006-291X(92)90501-B

Biochemical and Biophysical Research Communications

Volume 183, Issue 2, 16 March 1992, Pages 443-448

https://doi.org/10.1016/0006-291X(92)90501-B Get rights and content

Abstract

We have purified to homogeneity the long-chain specific 3-hydroxyacyl-CoA dehydrogenase from mitochondrial membranes of human infant liver. The enzyme is composed of non-identical subunits of 71kDa and 47kDa within a native structure of 230kDa. The pure enzyme is active with 3-ketohexanoyl-CoA and gives maximum activity with 3-ketoacyl-CoA substrates of C₁₀ to C₁₆ acyl-chain length but is inactive with acetoacetyl-CoA. In addition to 3-hydroxyacyl-CoA dehydrogenase activity, the enzyme possesses 2-enoyl-CoA hydratase and 3-ketoacyl-CoA thiolase activities which cannot be separated from the dehydrogenase. None of these enzymes show activity with C₄ substrates but all are active with C₆ and longer acyl-chain length substrates. They are thus distinct from any described previously. This human liver mitochondrial membrane-bound enzyme catalyses the conversion of medium- and long-chain 2-enoyl-CoA compounds to: 1) 3-ketoacyl-CoA in the presence of NAD alone and 2) to acetyl-CoA (plus the corresponding acyl-CoA derivatives) in the presence of NAD and CoASH. It is therefore a multifunctional enzyme, resembling the beta-oxidation enzyme of E. coli, but unique in its membrane location and substrate specificity. We propose that its existence explains the repeated failure to detect any intermediates of mitochondrial beta-oxidation.

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Human liver long-chain 3-hydroxyacyl-coenzyme a dehydrogenase is a multifunctional membrane-bound beta-oxidation enzyme of mitochondria

Abstract

Biochim. Biophys. Acta

Anal. Biochem

J. Biol. Chem

Clin. Chim. Acta

J. Biol. Chem

J. Biol. Chem

Gene (Amst.)

J. Biol. Chem

J. Biol. Chem

J. Biol. Chem

J. Inher. Metab. Dis

Pediatr. Res