Details

Autor(en) / Beteiligte

• Schram, André W.
• Goldfischer, Sidney
• Carlo W. T. Van Roermund
• Brouwer-Kelder, Elisabeth M.
• Collins, Janna
• Hashimoto, Takashi
• Hugo S. A. Heymans
• Van Den Bosch, Henk
• Ruud B. H. Schutgens
• Tager, Joseph M.
• Ronald J. A. Wanders

Titel

Human Peroxisomal 3-oxoacyl-coenzyme A Thiolase Deficiency

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1987-04, Vol.84 (8), p.2494-2496

Ort / Verlag

Washington, DC: National Academy of Sciences of the United States of America

Erscheinungsjahr

1987

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• We investigated the peroxisomal β -oxidation system in liver from a patient with clinical features similar to those in the cerebrohepatorenal (Zellweger) syndrome and with elevated levels in body fluids of very-long-chain fatty acids and intermediates in the biosynthesis of bile acids. The peroxisomal β -oxidation of fatty acids, measured as the cyanide-insensitive formation of [14C]acetyl units from [14C]palmitoyl-CoA, was very low in the patient (<10% of the values in control subjects). Immunoblotting experiments using antibodies to peroxisomal β -oxidation enzymes indicated that peroxisomal 3-oxoacyl-CoA thiolase (acyl-CoA:acetyl-CoA C-acyltransferase, EC 2.3.1.16) was deficient. Addition of purified rat-liver peroxisomal 3-oxoacyl-CoA thiolase to a reaction mixture containing liver homogenate from the patient restored peroxisomal β -oxidation. We conclude that the deficiency of peroxisomal 3-oxoacyl-CoA thiolase is responsible for the very low peroxisomal β -oxidation activity and for the accumulation of very-long-chain fatty acids and intermediates in the biosynthesis of bile acids. Furthermore, the finding that both very-long-chain fatty acids and abnormal bile acids accumulate in this patient suggests that a single peroxisomal 3-oxoacyl-CoA thiolase is involved in the oxidative chain shortening of both very-long-chain fatty acids and the coprostanoic acids.