Mitochondrial trifunctional protein deficiency. Catalytic heterogeneity of the mutant enzyme in two patients.
J Clin Invest
; 93(4): 1740-7, 1994 Apr.
Article
em En
| MEDLINE
| ID: mdl-8163672
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acetil-CoA C-Aciltransferase
/
Enoil-CoA Hidratase
/
3-Hidroxiacil-CoA Desidrogenases
/
Mitocôndrias
Limite:
Humans
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
1994
Tipo de documento:
Article
País de afiliação:
Japão