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Biomedical subjects

S Miyazawa

Publications and source records attributed to S Miyazawa.

At least 109 records · Page 6Linked to original sources
PubMed1982

Reduction of beta-oxidation capacity of rat liver mitochondria by feeding orotic acid.

Rats were maintained on fat-free high carbohydrate diets either with or without orotic acid (1%, w/w), pantethine (1%, w/w), adenine (0.25%, w/w), and/or p-chlorophenoxyisobutyrate (0.25%, w/w). Oxidation of fatty acid by liver mitochondria was inhibited to less than half that of the control after administration of orotic acid. Activities of acyl-CoA dehydrogenases were markedly decreased by orotic acid administration, but the following enzyme activities were not, or only slightly decreased: acyl-CoA synthetase, carnitine acyltransferases, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase and 3-ketoacyl-CoA thiolase. Simultaneous addition of pantethine in the orotic acid-containing diet prevented induction of fatty liver. It also prevented decreases in fatty acid oxidation capacity and acyl-CoA dehydrogenase activity. Introduction of adenine or p-chlorophenoxyisobutyrate, which reverse orotic acid-induced fatty liver, reversed oxidation and acyl-CoA dehydrogenase activities to control levels. The oxidation capacity of the peroxisomal system remained unchanged after administration of orotic acid.

Acyl-CoA Dehydrogenases↗
PubMed1982

Riboflavin deficiency and beta-oxidation systems in rat liver.

Weanling rats were fed a riboflavin-deficient diet. The mitochondrial fatty acid oxidation in liver was depressed in riboflavin deficiency but restored after supplementation of riboflavin. Among the enzymes involved in this system, only the acyl-CoA dehydrogenase (EC 1.3.99.2 and 1.3.99.3) activities varied with the change in fatty acid oxidation. An accumulation of the apoforms of acyl-CoA dehydrogenases was found in riboflavin deficiency. The levels of electron transfer flavoprotein and other enzymes involved in the beta-oxidation system remained unchanged. The peroxisomal fatty acid oxidation and levels of individual enzymes of this system remained constant. No accumulation of the apoform of acyl-CoA oxidase was observed under simple, riboflavin-deficient conditions. However, accumulation of a large amount of apo-acyl-CoA oxidase was observed when the peroxisomal system was induced by administration of a peroxisome proliferator, di(2-ethylhexyl)phthalate, under riboflavin-deficient conditions.

Acyl-CoA Oxidase↗
PubMed1982

Biosynthesis of enzymes of peroxisomal beta-oxidation.

Male Wistar rats were fed a diet with or without di(2-ethylhexyl)phthalate (DEHP), a peroxisome proliferator, for 2 weeks. The increases in the individual enzymes of the hepatic peroxisomal beta-oxidation system after administration of DEHP were 31- to 33-fold. It was found by in vivo experiments using L-[4,5-3H]leucine and the immunoprecipitation technique that the rates of synthesis of the enzymes were 16- to 20-fold higher and those of degradation were 1.7- to 1.9-fold lower in the DEHP group. The translation rates of these enzymes in vitro with liver RNA in the reticulocyte-lysate system were 12- to 14-fold higher in the DEHP group. Short-term kinetic labeling experiments on acyl-CoA oxidase consisting of three subunits were conducted in vivo to explore the biogenesis of peroxisomes. The label was found in the biggest subunit of the enzyme in the supernatant fraction shortly after the label injection, but was distributed to the smaller subunits later. The labeling in the smaller subunits in the peroxisomal fraction was greater than that of the supernatant. The distribution of the label among the subunits in these subcellular fractions was the same as that of the protein amounts 1 day after the label injection. This paper reports that the increase in the quantities of peroxisomal enzymes upon administration of DEHP is mainly due to the increase in their synthesis rates caused by the increase in amounts of mRNA coding for these enzymes.

Acyl-CoA Oxidase↗
PubMed1981

alpha-Amanitin inhibits the oxidation of long chain fatty acids in mouse liver.

It was found that the injection of the extract of Amanita virosa mushroom into mice resulted in the inhibition of long chain fatty acid oxidation by liver mitochondria. The inhibition principle was identified as alpha-amanitin. The inhibition was observed several hours after the injection of alpha-amanitin at the level of about 0.2 mg/kg, which corresponded to LD50. Activities of carnitine acyltransferases, acyl-CoA dehydrogenases, enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase remained constant. Using fatty acids with various carbon chain lengths as substrates, the oxidation of long chain fatty acids was markedly inhibited with accompanying disappearance of the carnitine-dependent component. The decreases in the oxidation of medium and short chain fatty acids were less marked. It is suggested, therefore, that the site of the inhibition is the transport of long chain acylcarnitines. Peroxisomal beta-oxidation was not affected by the alpha-amanitin treatment.

Amanitins↗
PubMed1981

Properties of peroxisomal 3-ketoacyl-coA thiolase from rat liver.

Peroxisomal 3-ketoacyl-CoA thiolase has a molecular weight of 89,000 and consists of 2 polypeptide chains of identical size. The enzyme has no interchain disulfide bonds and is reversibly dissociated to an inactive monomer in the cold. Mitochondrial 3-ketoacyl-CoA thiolase and acetoacetyl-CoA specific thiolase have molecular weights of 154,000 and 149,000, respectively. They each consist of 4 polypeptide chains of identical size. Peroxisomal thiolase and mitochondrial 3-ketoacyl-CoA thiolase operate by a ping-pong mechanism. The catalytic properties, including substrate specificity, of the peroxisomal enzyme were compared to those of mitochondrial 3-ketoacyl-CoA thiolase.

Acetyl-CoA C-Acetyltransferase↗
PubMed1981

Purification and properties of rat liver acyl-CoA dehydrogenases and electron transfer flavoprotein.

Three acyl-CoA dehydrogenases and electron transfer flavoprotein, which catalyze the initial step of mitochondrial fatty acid beta-oxidation, were purified from livers of rats fed a diet containing di(2-ethylhexyl)phthalate. Three acyl-CoA dehydrogenases, classified into short chain, general, and long chain acyl-CoA dehydrogenases on the basis of their substrate specificities, each consisted of four subunits of identical size: the molecular weights of the native enzymes were 169,000 for short chain acyl-CoA dehydrogenase, 182,000 for general acyl-CoA dehydrogenase, and 168,000 for long chain acyl-CoA dehydrogenase. Electron transfer flavoprotein with a molecular weight of 57,000 consisted of heterogeneous subunits with molecular weight of 33,500 and 25,100. The catalytic properties and molecular structures of rat liver acyl-CoA dehydrogenases were similar to those of the enzymes purified from other mammalian tissues such as pig heart, pig liver, and beef kidney. We could not obtain purified preparations of the three acyl-CoA dehydrogenases from livers of the control rats although the three dehydrogenases were completely separated from each other. The enzymes from the control and the di(2-ethylhexyl)phthalate-treated rats were compared and no differences were found in molecular sizes of the native enzymes and of their subunits, substrate specificities and immunochemical reactivities.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed1981

Induction of acyl-CoA dehydrogenases and electron transfer flavoprotein and their roles in fatty acid oxidation in rat liver mitochondria.

The capacity of mitochondrial beta-oxidation and activities of three acyl-CoA dehydrogenases and electron transfer flavoprotein in rat liver were increased after administration of peroxisome proliferators such as di(2-ethylhexyl)phthalate or p-chlorophenoxyisobutyrate. Oxygen consumption by mitochondrial beta-oxidation with palmitate, palmitoyl-CoA or palmitoylcarnitine was in the range of 0.27-0.41 mumol O2/min per g liver and the dehydrogenase activity with palmitoyl-CoA was 0.56 mumol/min per g liver. These activities were increased, after administration of peroxisome proliferators, to 0.80-1.23 mumol O2/min per g liver and 1.06-1.08 mumol/min per g liver, respectively. The time required to reach half-maximal induction of the three acyl-CoA dehydrogenases and electron transfer flavoprotein after administration of di(2-ethylhexyl)phthalate was about 5 days. On the withdrawal of the agent, the activities of these flavoproteins decreased to the control levels with half-lives of about a day.

Animals↗
PubMed1981

Induction of a novel long-chain acyl-CoA hydrolase in rat liver by administration of peroxisome proliferators.

The activity of long-chain acyl-CoA hydrolase in rat liver was increased by the administration of peroxisome proliferators, such as ethyl p-chlorophenoxyisobutyrate, di(2-ethylhexyl)phthalate or acetylsalicylic acid. The induced activity was mainly confined in the soluble fluid after the subcellular fractionation. The enzyme was purified nearly to homogeneity from livers of rats treated with di(2-ethylhexyl)phthalate. The specific activity of the final preparation was 247 mumol palmitoyl-CoA hydrolyzed min-1 mg protein-1. The molecular weight of the native enzyme was estimated to be 150 000 by gel filtration and that of the subunits was 41 000 by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The activity of the enzyme was not increased but inhibited by bovine serum albumin or Triton X-100. The molecular and catalytic properties of the enzyme suggest that the induced enzyme was different from mitochondrial and microsomal long-chain acyl-CoA hydrolyses in liver.

Animals↗