Characteristics of peroxisome proliferation: co-induction of peroxisomal fatty acid oxidation-related enzymes with microsomal laurate hydroxylase.
The profile of the changes in the peroxisomal fatty acid oxidation activity in rat liver was compared with that in microsomal omega-oxidation under various conditions such as a 2-week administration of phenoxyacetic acid derivatives and perfluorinated compounds, short and long-term administration of clofibrate and bezafibrate, high-fat diet feeding, starvation and diabetes. The results were summarized as follows: 1) when phenoxyacetic acid derivatives and perfluorinated compounds were administered, there was a significant correlation in the increase of the activities between peroxisomal fatty acid oxidation and microsomal omega-oxidation. 2) On the long-term administration (79 weeks) of peroxisome proliferators the activities of the enzymes were significantly reduced, but the levels were still higher than the control level in a similar manner. 3) On high-fat diet feeding the patterns of the changes in the activities of peroxisomal fatty acid oxidation, carnitine acetyltransferase and microsomal omega-oxidation were similar to each other, differing from the changes in the activities of microsomal aminopyrin demethylase and mitochondrial carnitine palmitoyltransferase. 4) Under starved and diabetic conditions, co-induction of peroxisomal fatty acid oxidation and microsomal omega-oxidation was observed. From these results it is suggested that 1) the biosynthesis of these enzymes would be regulated on the gene expression of the nearby domain and 2) peroxisomal fatty acid oxidation and microsomal omega-oxidation were co-operatively regulated in order to achieve fatty acid metabolism smoothly.
Department of Clinical Biochemistry, Tokyo College of Pharmacy, Japan.
H
H
Kozuka
T
T
Watanabe
S
S
Horie
J
J
Yamada
T
T
Suga
T
T
Ikeda
D000818:Animals; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D005227:Fatty Acids; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A