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

https://doi.org/10.1016/0006-291X(92)90501-BGet 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.

References (24)

  • M. El-Fakhri et al.

    Biochim. Biophys. Acta

    (1982)
  • C. Thorpe

    Anal. Biochem

    (1986)
  • P.M. Palosaari et al.

    J. Biol. Chem

    (1990)
  • B. Middleton et al.

    Clin. Chim. Acta

    (1983)
  • B.E. Noyes et al.

    J. Biol. Chem

    (1973)
  • T. Osumi et al.

    J. Biol. Chem

    (1985)
  • W.M. Nuttley et al.

    Gene (Amst.)

    (1988)
  • S-Y. Yang et al.

    J. Biol. Chem

    (1983)
  • S. Pawar et al.

    J. Biol. Chem

    (1981)
  • B. Sumegi et al.

    J. Biol. Chem

    (1984)
  • R.J.A. Wanders et al.

    J. Inher. Metab. Dis

    (1990)
  • S. Jackson et al.

    Pediatr. Res

    (1991)
  • Cited by (131)

    • Functional characterization of a novel gene, Hc-dhs-28 and its role in protecting the host after Haemonchus contortus infection through regulation of diapause formation

      2020, International Journal for Parasitology
      Citation Excerpt :

      Moreover, the 162 site was also the proton binding site (Kim et al., 2009). The 3-hydroxyacyl CoA dehydrogenase participates mainly in peroxisomal and mitochondrial fatty acid β-oxidation which is very important for the fatty acid metabolism (Carpenter et al., 1992; Poirier et al., 2006). The human peroxisome fatty acid β-oxidation pathway consisted of three genes, acox-1, mfe-2 and scp-x (Poirier et al., 2006).

    • Mitochondrial β-oxidation of saturated fatty acids in humans

      2019, Mitochondrion
      Citation Excerpt :

      This shortened acyl-coA ester may start again the oxidation cycle. ( Fig. 3) In humans, a single enzyme catalyzes the three last steps in the β-oxidation of long-chain fatty acids, the mitochondrial trifunctional protein (MTP) complex (Carpenter et al., 1992). The MTP complex has been purified to homogeneity from mitochondrial membranes of human infant liver.

    • Elimination of the unnecessary: Intra- and extracellular signaling by anionic phospholipids

      2017, Biochemical and Biophysical Research Communications
      Citation Excerpt :

      Importantly, there are concentration thresholds of PS on the surface, needed for the recognition of apoptotic cells, in order to initiate phagocytosis [58]. The existence of a threshold mechanism is essential for the prevention of excessive phagocytosis of non-apoptotic cells which may transiently present externalize PS on their surface [47,58,24,59,60]. During inflammation, massive production of reactive oxygen species (ROS) creates pro-oxidant environments potentially favoring PS oxidation [61], yet for phagocytosis, externalized PS is not required to be oxidized.

    View all citing articles on Scopus
    View full text