Mitochondrial trifunctional protein deficiency. Catalytic heterogeneity of the mutant enzyme in two patients

J Clin Invest. 1994 Apr;93(4):1740-7. doi: 10.1172/JCI117158.


We examined the enzyme protein and biosynthesis of human trifunctional protein harboring enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase activity in cultured skin fibroblasts from two patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. The following results were obtained. (a) In cells from patient 1, immunoblot analysis and pulse-chase experiments indicated that the content of trifunctional protein was < 10% of that in control cells, due to a very rapid degradation of protein newly synthesized in the mitochondria. The diminution of trifunctional protein was associated with a decreased activity of enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase, when measured using medium-chain to long-chain substrates. (b) In cells from patient 2, the rate of degradation of newly synthesized trifunctional protein was faster than that in control cells, giving rise to a trifunctional protein amounting to 60% of the control levels. The 3-hydroxy-acyl-CoA dehydrogenase activity with medium-chain to long-chain substrates was decreased drastically, with minor changes in activities of the two other enzymes. These data suggest a subtle abnormality of trifunctional protein in cells from patient 2. Taken together, the results obtained show that in both patients, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is caused by an abnormality in the trifunctional protein, even though there is a heterogeneity in both patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases / deficiency*
  • 3-Hydroxyacyl CoA Dehydrogenases / genetics
  • Acetyl-CoA C-Acyltransferase / deficiency*
  • Acetyl-CoA C-Acyltransferase / genetics
  • Cells, Cultured
  • Enoyl-CoA Hydratase / deficiency*
  • Enoyl-CoA Hydratase / genetics
  • Fibroblasts / enzymology
  • Humans
  • Immunoblotting
  • Mitochondria / metabolism*
  • Molecular Weight
  • Mutation
  • Oxidation-Reduction
  • Palmitic Acid
  • Palmitic Acids / metabolism


  • Palmitic Acids
  • Palmitic Acid
  • 3-Hydroxyacyl CoA Dehydrogenases
  • Acetyl-CoA C-Acyltransferase
  • Enoyl-CoA Hydratase