title: Mitochondrial trifunctional protein deficiency. Catalytic heterogeneity of the mutant enzyme in two patients.
abstract: 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.
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, Nagano, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kamijo
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
authors.forename: T
authors.initials: T
authors.lastname: Aoyama
authors.forename: A
authors.initials: A
authors.lastname: Komiyama
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency* / Q000235:genetics; D000102:Acetyl-CoA C-Acyltransferase / Q000172:deficiency* / Q000235:genetics; D002478:Cells, Cultured; D004746:Enoyl-CoA Hydratase / Q000172:deficiency* / Q000235:genetics; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D015151:Immunoblotting; D008928:Mitochondria / Q000378:metabolism*; D008970:Molecular Weight; D009154:Mutation; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism
chemical_list: D010169:Palmitic Acids; D019308:Palmitic Acid; D015094:3-Hydroxyacyl CoA Dehydrogenases; D000102:Acetyl-CoA C-Acyltransferase; D004746:Enoyl-CoA Hydratase