Abstract
The effect of a peroxisome proliferator, clofibrate, on mitochondrial 2,4-dienoyl-CoA reductases was studied in rat liver. The specific activity of reductase measured with 2,4-hexadienoyl-CoA as the substrate increased 2.9-fold in the liver homogenate and 2.5-fold in the mitochondrial extract, whereas acyl-CoA oxidase activity increased 13-fold and delta 3, delta 2-enoyl-CoA isomerase activity, 25-fold in the homogenate. Chromatography of the rat liver homogenate on hydroxylapatite, which separates the mitochondrial isoforms (M(r) 120,000 and M(r) 60,000) showed that the M(r) 60,000 isoform increased 3.5-fold and the M(r) 120,000 isoform 6-fold. When the isoforms were assayed with 2,4-hexadienoyl-CoA and trans-2,cis-4,7,10,13,16,19-docosaheptaenoyl-CoA, the activity ratios of C6 to C22 were 1.5-2.1 for the both isoforms isolated from livers of either control or clofibrate-treated rats. A quantitative immunological experiment with the antibody for the 120,000 reductase in the mitochondrial extracts showed a 6.9-fold increase in the signal, confirming the observation that this isoform is induced more than the other. The mRNA levels of reductase, isomerase, and peroxisomal multifunctional enzyme (MFE) were found to rise in a parallel manner when analyzed by in situ or slot hybridizations, which suggests that the increase was mediated by the same mechanism. Peroxisome proliferators have been shown to increase the mRNA levels of MFE by inducing peroxisome proliferator-activated receptor (PPAR)-mediated expression of the corresponding gene. The short-chain delta 3, delta 2-enoyl-CoA isomerase and the M(r) 120,000 reductase are exceptions among the mitochondrial beta-oxidation proteins, which usually show only a minor response to peroxisome proliferators.
Highlights
The physiological significance of isoforms in separate organelles can be envisaged, but their functions within the same organelle are less obvious
Peroxisome proliferators have been shown to increase the mRNA levels of multifunctional enzyme (MFE) by inducing peroxisome microsomal cytochrome P45OIVA1 [6], which is the enzyme for w-hydroxylation of fatty acids, and the cytosolic fatty acid-binding protein [7]
As 2,4-dienoylCoA reductase is considered to be the key enzyme in the degradation of unsaturated fatty acids, it is difficult, in view of the change detected in reductase activity, to explain the observed increase in P-oxidation of polyenoyl-CoAs
Summary
The physiological significance of isoforms in separate organelles can be envisaged, but their functions within the same organelle are less obvious. The mRNA levels of reductase, isomerase, and are affected by the treatment, among them the peroxisomal multifunctional enzyme (MFE) were found to rise in a parallel manner when analyzed by in situ or slot hybridizations, which suggests that the increase was mediated by the same mechanism. Peroxisome proliferators have been shown to increase the mRNA levels of MFE by inducing peroxisome microsomal cytochrome P45OIVA1 [6], which is the enzyme for w-hydroxylation of fatty acids, and the cytosolic fatty acid-binding protein [7]. The short-chain A3,A2-enoyl-CoA isomerase and the M, 120,000 reductase are exceptions among the mitochondrial P-oxidation proteins, which usually show only a minor response to peroxisome pro1iferators.- Hakkola, mechanism has been partly characterized. Along with all the peroxisomal 0-oxidation enzymes, mitochondrial short-chain A3,A*-enoyl-CoA isomerase activity [9] and
Sign-in/Register to view highlights & summary 
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call