Effect of choline-deficiency and methotrexate administration on peroxisomal beta-oxidation, palmitoyl-CoA hydrolase activity and the glutathione content in rat liver.

Abstract

Hepatic metabolism of long-chain fatty acids was studied in male rats fed a defined choline-deficient (CD) diet with and without choline and after methotrexate (MTX) administration. Peroxisomal beta-oxidation was increased approximately 4-fold in the peroxisome-enriched fraction of CD-fed animals, whereas the catalase activity was increased 1.3-fold. The urate oxidase activity was marginally affected. The CD-fed rats also revealed elevated capacity for hydrolysis of palmitoyl-CoA in the cytosolic fraction (2.0-fold), whereas the microsomal palmitoyl-CoA hydrolase activity was decreased. Notably, the increased peroxisomal beta-oxidation, the catalase activity and palmitoyl-CoA hydrolase activities (the membrane-bounded and cytosolic) were almost fully prevented by adding choline to the CD-diet. Thus, the change in these enzyme activities appears to be a consequence of a choline-deficiency provoked by the CD diet. MTX administration of normal fed rats (ND diet) had no effects on the peroxisomal beta-oxidation, catalase activity and urate oxidase activity. MTX treatment of the ND-fed animals, however, increased the mitochondrial palmitoyl-CoA hydrolase activity and decreased the microsomal enzyme activity. As choline-deficiency and MTX increased the hepatic lipid level, the overall results suggest that fat accumulation is not an 'induction signal' for increased peroxisomal beta-oxidation. The CD diet alone increased the reduced glutathione content in liver, whereas MTX did not significantly change this level. Whether the changes of H2O2-generating peroxisomal oxidation of long-chain fatty acids may be an important step in a chain of events, which eventually results in tumour formation by choline-deficiency, should be considered.

• Authors: R K Berge, N Aarsaether, A Aarsland, A Svardal, P M Ueland
• Journal: Carcinogenesis (Carcinogenesis) Vol. 9 Issue 4 Pg. 619-24 (Apr 1988) ISSN: 0143-3334 [Print] England
• PMID: 2895692 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fatty Acids, Nonesterified
• Acyltransferases
• Thiolester Hydrolases
• Palmitoyl-CoA Hydrolase
• Glutathione
• Methotrexate

Topics

• Acyltransferases (metabolism)
• Animals
• Choline Deficiency (metabolism)
• Fatty Acids, Nonesterified (metabolism)
• Glutathione (metabolism)
• Liver (drug effects, metabolism)
• Male
• Methotrexate (pharmacology)
• Microbodies (drug effects, metabolism)
• Oxidation-Reduction
• Palmitoyl-CoA Hydrolase (metabolism)
• Rats
• Rats, Inbred Strains
• Reference Values
• Subcellular Fractions (enzymology)
• Thiolester Hydrolases (metabolism)