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We 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 [14C]acetyl units from [14C]palmitoyl-CoA, was very low in the patient (less than 10% of the values in control subjects). Immunoblotting experiments using antibodies to peroxisomal beta-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 beta-oxidation. We 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.
A W Schram, and
S Goldfischer, and
C W van Roermund, and
E M Brouwer-Kelder, and
J Collins, and
T Hashimoto, and
H S Heymans, and
H van den Bosch, and
R B Schutgens, and
J M Tager
April 1990,
The Journal of clinical investigation,
A W Schram, and
S Goldfischer, and
C W van Roermund, and
E M Brouwer-Kelder, and
J Collins, and
T Hashimoto, and
H S Heymans, and
H van den Bosch, and
R B Schutgens, and
J M Tager
November 1988,
Nucleic acids research,
A W Schram, and
S Goldfischer, and
C W van Roermund, and
E M Brouwer-Kelder, and
J Collins, and
T Hashimoto, and
H S Heymans, and
H van den Bosch, and
R B Schutgens, and
J M Tager
May 1989,
Nucleic acids research,
A W Schram, and
S Goldfischer, and
C W van Roermund, and
E M Brouwer-Kelder, and
J Collins, and
T Hashimoto, and
H S Heymans, and
H van den Bosch, and
R B Schutgens, and
J M Tager
January 1995,
Human heredity,
A W Schram, and
S Goldfischer, and
C W van Roermund, and
E M Brouwer-Kelder, and
J Collins, and
T Hashimoto, and
H S Heymans, and
H van den Bosch, and
R B Schutgens, and
J M Tager
August 1994,
The Journal of biological chemistry,
A W Schram, and
S Goldfischer, and
C W van Roermund, and
E M Brouwer-Kelder, and
J Collins, and
T Hashimoto, and
H S Heymans, and
H van den Bosch, and
R B Schutgens, and
J M Tager
January 1998,
Ryoikibetsu shokogun shirizu,
A W Schram, and
S Goldfischer, and
C W van Roermund, and
E M Brouwer-Kelder, and
J Collins, and
T Hashimoto, and
H S Heymans, and
H van den Bosch, and
R B Schutgens, and
J M Tager
July 1994,
Yeast (Chichester, England),
A W Schram, and
S Goldfischer, and
C W van Roermund, and
E M Brouwer-Kelder, and
J Collins, and
T Hashimoto, and
H S Heymans, and
H van den Bosch, and
R B Schutgens, and
J M Tager
August 1991,
Biochimica et biophysica acta,
A W Schram, and
S Goldfischer, and
C W van Roermund, and
E M Brouwer-Kelder, and
J Collins, and
T Hashimoto, and
H S Heymans, and
H van den Bosch, and
R B Schutgens, and
J M Tager
September 1994,
Yeast (Chichester, England),
A W Schram, and
S Goldfischer, and
C W van Roermund, and
E M Brouwer-Kelder, and
J Collins, and
T Hashimoto, and
H S Heymans, and
H van den Bosch, and
R B Schutgens, and
J M Tager
July 1990,
The Journal of clinical investigation,
