Peroxisomal Fatty Acid Β-oxidation Research Articles

Enhanced peroxisomal β-oxidation of fatty acids and glutathione metabolism in rats exposed to phenoxyacetic acids

Peroxisomal β-oxidation of fatty acids and the activities of glutathione-metabolizing enzymes in rat liver were measured after administration of 2,4-dichlorophenoxyacetic acid (2,4-D), 4-chloro-2-methylphenoxyacetic acid (MCPA), clofibrate [ethyl], 2-( p-chlorophenoxy)-2-methylpropionate], glyphosate ( N-phosphonomethyl glycine, a herbicide not structurally related to phenoxy acids) or saline for 14 days. β-Oxidation increased by 6-fold in the group given clofibrate, 3-fold in the 2,4-D-treated group, and 2-fold in the MCPA-treated group over the level in the controls (saline-treated). Glyphosate did not increase β-oxidation. No significant change in reduced glutathione content from that in controls was found in any of the treated groups. Glutathione reductase activity increased by about 40% after administration of either 2,4-D or MCPA, and glutathione peroxidase activity increased by 30% in animals given MCPA. A slight decrease in glutathione S-transferase activity was found in the group treated with clofibrate. The marked increases in peroxisomal β-oxidation of fatty acids were accompanied by only minor changes in the activities of enzymes involved in glutathione-dependent inactivation of organic hydroperoxides and other oxygen-centred reactive agents.

Glucagon and fasting do not activate peroxisomal fatty acid β-oxidation in rat liver

In a study of the endocrine control of peroxisomes, the effects of acute glucagon treatment and fasting on hepatic peroxisomal β-oxidation in rats have been investigated. The activity of the rate-limiting peroxisomal β-oxidation enzyme, fatty acyl-CoA oxidase, was measured to determine whether activation of peroxisomal β-oxidation could account for the increase in total hepatic fatty acid oxidation following acute glucagon exposure. Catalase, a peroxisomal enzyme not directly involved in β-oxidation, was also measured as a control for total peroxisomal activity. No changes with acute glucagon treatment of intact animals were observed with either activity as measured in liver homogenates or partially purified peroxisomal fractions. These observations indicate the lack of acute control by glucagon of peroxisomal function at the level of total enzyme activity. Previous work on the effects of fasting on hepatic fatty acid β-oxidation [ H. Ishii, S. Horie, and T. Suga (1980), J. Biochem., 87, 1855–1858] suggested an enhanced role for the peroxisomal β-oxidation pathway during starvation. It was found that the peroxisomal β-oxidation system, as measured by fatty acyl-CoA oxidase activity, does increase with duration of fast when expressed on a per gram wet weight liver basis. However, when this activity is expressed as total liver capacity, a decline in activity with increasing duration of fast is observed. Furthermore, this decline in peroxisomal capacity parallels the decline in total liver capacity for citrate synthase, a mitochondrial matrix enzyme, and total liver protein. These data indicate that peroxisomal β-oxidation activity is neither stimulated nor even preferentially spared from proteolysis during fasting.

Lipid metabolism in rainbow trout ( Salmo gairdnerii) fed diets containing partially hydrogenated fish oil

1. 1. Rainbow trout were fed diets containing either 15% crude fish oil (CFO), 11.5% partially hydrogenated fish oil (PHFO) and 3.5% CFO, or 15% PHFO. 2. 2. Fish maintained on PHFO exhibited the highest death and lowest growth rates. CFO- and PHFO + CFO-fed fish had similar death and growth rates. After 15 months, PHFO + CFO fish had larger hearts and livers than fish fed CFO. 3. 3. Plasma cholesterol and triglyceride concentrations were similar in CFO and PHFO + CFO-fed fish and lowest in the group fed PHFO. 4. 4. Tissue lipids of PHFO + CFO fish were richer in 18:1 and less unsaturated than those of the CFO group. PHFO was richer in 22:1 than CFO, but the 22:1 contents of tissue lipids of PHFO + CFO and CFO fish were similar and less than those of the dietary oils. 5. 5. Cyanide-insensitive palmitoyl-CoA oxidation activity in liver was highest in trout fed the PHFO + CFO diet, while carnitine palmitoyltransferase was not affected by diet. 6. 6. It is suggested that the excess of long chain monoenes in relation to polyunsaturates in a PHFO + CFO diet causes an induction of the peroxisomal β-oxidation of fatty acids in fish liver.

Effects of antilipolytic agents on peroxisomal β-oxidation of fatty acids in rat liver

Effects of antilipolytic agents on peroxisomal β-oxidation of fatty acids in rat liver

Subcellular distribution of coenzyme A: Evidence for a separate coenzyme a pool in peroxisomes

Summary Subcellular fractions enriched in peroxisomes, that were prepared by differential centrifugation, contained more free and total (free plus esterified) CoA than could be accounted for by mitochondrial contamination. Separation of peroxisomes and mitochondria by isopycnic centrifugation of fractions enriched in peroxisomes resulted in a bimodal distribution of free and total CoA in which both peak fractions coincided with the fractions that contained most of the peroxisomal and mitochondrial marker enzyme activities respectively. These results indicate that peroxisomes have a separate CoA-pool. This CoA appears to be available for the thiolase reaction during peroxisomal β-oxidation of fatty acids but not for the activation of fatty acids by the peroxisomal acyl-CoA synthetase.

19] Assay of peroxisomal β-oxidation of fatty acids

Publisher Summary This chapter describes the assay of peroxisomal β-oxidation of fatty acids. In the presence of palmitoyl-CoA, the reduction of NAD to NADH that occurs at the third step of the β-oxidation spiral is measured spectrophotometrically. Assay method may be applied to mitochondria by omitting Triton X-100 and including final concentrations of 0.25 M sucrose, and 1 mM carnitine in the assay and using freshly isolated organelles diluted with 0.25 M sucrose. Under these conditions peroxisomes show somewhat submaximal activity. The spectrophotometric assay is strictly linear with the amount of enzyme and the results are obtained immediately. The radioactivity assay is more sensitive. The two assay methods give similar results in measuring the distribution of peroxisomal β-oxidation during cell fractionation experiments measuring the effect of hypolipidemic drugs on the activity of peroxisomal B-oxidation. It is found that peroxisomal β-oxidation does not require carnitine, is insensitive to freezing, and is not inhibited by 1 mM KCN, when assayed in homogenates or subcellular fractions.

Possible involvement of fatty acid binding protein in peroxisomal β-oxidation of fatty acids

The localization of β-oxidation of fatty acids in isolated peroxisomes from rat liver was investigated. The enzyme system is soluble in the luminal compartment and carnitine does not appear to be involved in the transfer of the CoA derivatives through the peroxisomal membrane. Experiments involving proteolysis, inhibitors and competitive inhibition suggest that a fatty acid binding protein is responsible for the carrier process. This carrier protein seems to be present in increased amounts both in the supernatant and in the peroxisomes after clofibrate induction.

Field emission observations of carbon on tantalum: R. Klein and L. B. Leder, J. Chem. Phys., 38 (8), 15 April 1963, 1863–1872

Perrault syndrome is a recessive disorder characterized by ovarian dysgenesis in females, sensorineural deafness in both males and females, and in some patients, neurological manifestations. No genes for Perrault syndrome have heretofore been identified. A small family of mixed European ancestry includes two sisters with well-characterized Perrault syndrome. Whole-exome sequencing of genomic DNA from one of these sisters revealed exactly one gene with two rare functional variants: HSD17B4, which encodes 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4), also known as D-bifunctional protein (DBP). HSD17B4/DBP is a multifunctional peroxisomal enzyme involved in fatty acid β-oxidation and steroid metabolism. Both sisters are compound heterozygotes for HSD17B4 c.650A>G (p.Y217C) (maternal allele) and HSB17B4 c.1704T>A (p.Y568X) (paternal allele). The missense mutation is predicted by structural analysis to destabilize the HSD17B4 dehydrogenase domain. The nonsense mutation leads to very low levels of HSD17B4 transcript. Expression of mutant HSD17B4 protein in a compound heterozygote was severely reduced. Mutations in HSD17B4 are known to cause DBP deficiency, an autosomal-recessive disorder of peroxisomal fatty acid β-oxidation that is generally fatal within the first two years of life. No females with DBP deficiency surviving past puberty have been reported, and ovarian dysgenesis has not previously been associated with this illness. Six other families with Perrault syndrome have wild-type sequences of HSD17B4. These results indicate that Perrault syndrome and DBP deficiency overlap clinically; that Perrault syndrome is genetically heterogeneous; that DBP deficiency may be underdiagnosed; and that whole-exome sequencing can reveal critical genes in small, nonconsanguineous families.