Biosynthesis and maturation of peroxisomal beta-oxidation enzymes in fibroblasts in relation to the Zellweger syndrome and infantile Refsum disease.

AUTOR(ES)

Schram, A W

RESUMO

The biosynthesis of the peroxisomal enzymes acyl-CoA oxidase, 3-oxoacyl-CoA thiolase (acetyl-CoA acyl-transferase, EC 2.3.1.16), and catalase (EC 1.11.1.6) was studied in cultured skin fibroblasts from a control subject and from patients with Zellweger syndrome and the infantile form of Refsum disease, inherited disorders in which peroxisomes are deficient and certain peroxisomal functions are impaired. The results of continuous labeling and pulse-chase experiments indicate that in control fibroblasts, as in rat liver, acyl-CoA oxidase is synthesized as a 72-kDa percursor that is converted to two polypeptides of 52 and 20 kDa and 3-oxoacyl-CoA thiolase is synthesized as a 44-kDa precursor that is converted to the 41-kDa mature protein. In fibroblasts from the patients the precursors of the two enzymes are formed but their maturation is impaired, and they are rapidly degraded. In contrast, the biosynthesis of catalase is not impaired. We conclude that functional peroxisomes are required for the maturation and stability of acyl-CoA oxidase and 3-oxoacyl-CoA thiolase but not for catalase.

Documentos Relacionados

• Peroxisomal fatty acid beta-oxidation in relation to the accumulation of very long chain fatty acids in cultured skin fibroblasts from patients with Zellweger syndrome and other peroxisomal disorders.
• Oxidation of pristanic acid in fibroblasts and its application to the diagnosis of peroxisomal beta-oxidation defects.
• Metabolism of prostaglandin F2 alpha in Zellweger syndrome. Peroxisomal beta-oxidation is a major importance for in vivo degradation of prostaglandins in humans.
• Mitochondrial and peroxisomal beta-oxidation capacities of organs from a non-oilseed plant.
• Association of glyoxylate and beta-oxidation enzymes with peroxisomes of Saccharomyces cerevisiae.