Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency

Journal Article · Wed Apr 01 04:00:00 EST 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.8.2494· OSTI ID:6027679

Schram, A W; Goldfischer, S; Van Roermund, C W.T.; Brouwer-Kelder, E M; Collins, J; Hashimoto, T; Heymans, H S.A.; Van Den Bosch, H; Schutgens, R B.H.; Tager, J M; Wanders, R J.A.

The authors investigated the peroxisomal ..beta..-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 ..beta..-oxidation of fatty acids, measured as the cyanide-insensitive formation of (/sup 14/C)acetyl units from (/sup 14/C)palmitoyl-CoA, was very low in the patient (< 10% of the values in control subjects). Immunoblotting experiments using antibodies to peroxisomal ..beta..-oxidation enzymes indicated that peroxisomal 3-oxoaceyl-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 ..beta..-oxidation. They conclude that the deficiency of peroxisomal 3-oxoacyl-CoA thiolase is responsible for the very low peroxisomal ..beta..-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.

• Research Organization: Univ. of Amsterdam, Netherlands
• OSTI ID: 6027679
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:8; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
BILE ACIDS
BIOCHEMISTRY
BIOSYNTHESIS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CHEMISTRY
DIGESTIVE SYSTEM
DISEASES
DOSE-RESPONSE RELATIONSHIPS
ENZYME ACTIVITY
ENZYMES
GLANDS
HYDROXY COMPOUNDS
LABELLED COMPOUNDS
LIVER
METABOLIC DISEASES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDATION
PATHOGENESIS
PATIENTS
STEROIDS
STEROLS
SYNTHESIS
TRANSFERASES