Showing papers on "Acyl-CoA published in 1984"

Effect of long-chain fatty acyl-CoA on mitochondrial and cytosolic ATP/ADP ratios in the intact liver cell

Abstract: The effect of long-chain acyl-CoA on subcellular adenine nucleotide systems was studied in the intact liver cell. Long-chain acyl-CoA content was varied by varying the nutritional state (fed and starved states) or by addition of oleate. Starvation led to an increase in the mitochondrial and a decrease in the cytosolic ATP/ADP ratio in liver both in vivo and in the isolated perfused organ as compared with the fed state. The changes were reversed on re-feeding glucose in liver in vivo or on infusion of substrates (glucose, glycerol) in the perfused liver, respectively. Similar changes in mitochondrial and cytosolic ATP/ADP ratios occurred on addition of oleate, but, importantly, not with a short-chain fatty acid such as octanoate. It is concluded that long-chain acyl-CoA exerts an inhibitory effect on mitochondrial adenine nucleotide translocation in the intact cell, as was previously postulated in the literature from data obtained with isolated mitochondria. The physiological relevance with respect to pyruvate metabolism, i.e. regulation of pyruvate carboxylase and pyruvate dehydrogenase by the mitochondrial ATP/ADP ratio, is discussed.

Inhibition of the hormone-sensitive lipase in adipose tissue by long-chain fatty acyl coenzyme A.

Abstract: The effects of free fatty acids and fatty acyl esters of coenzyme A and carnitine on the activity of a hormone-sensitive lipase preparation made from pigeon adipose tissue were determined. Oleic acid (100 μM) resulted in a 40% inhibition of lipase activity A more potent inhibition of lipase activity was seen with long-chain fatty acyl CoA compounds. The concentration required for half-maximal inhibition with oleoyl CoA and palmitoyl CoA was 25–40 μM, whereas palmitoyl carnitine stimulated lipase activity. Activated lipase preparations (preincubated with Mg2+, ATP, cyclic AMP and protein kinase) were 4–6 times more sensitive to inhibition by oleoyl CoA than were nonactivated preparations. An increase in cellular levels of fatty acyl coenzyme A could, therefore, contribute to the feedback inhibition of lipolysis in adipose tissue.

Activation of polyunsaturated fatty acids by rat tissues in vitro

Abstract: The conversion of labeled palmitic, linoleic, arachidonic and docosahexaenoic acids to their respective acyl CoA's was studied in homogenates and microsomes of rat tissues. The highest activity, both in homogenates and microsomes, was seen in liver and heart. There was moderate activity in retina, brain, lung, kidney and testes and the lowest activity was found in spleen. Docosahexaenoic acid was activated much less actively in heart tissue than the other fatty acids. In all tissues examined, the highest activation was observed with arachidonic acid and the lowest with docosahexaenoic acid. Except for liver, those tissues that contained high levels of docosahexaenoic acid also had the highest activation capacity for this fatty acid.

Association of the liver peroxisomal fatty acyl-CoA beta-oxidation system with the synthesis of bile acids.

Abstract: The association of liver peroxisomal fatty acyl-CoA beta-oxidizing system (FAOS) with the synthesis of bile acids was investigated. When rats were given clofibrate, a peroxisome proliferator and stimulator of peroxisomal FAOS, the biosynthesis of bile acids was significantly increased. Di(2-ethylhexyl)phthalate, another peroxisome proliferator, also increased the biosynthesis of bile acids. On the other hand, administration of orotate, an inhibitor of mitochondrial FAOS activity, did not affect the biosynthesis. It is known that fatty acyl-CoA oxidase [EC 1.3.99.3] in peroxisomal FAOS conjugates with catalase [EC 1.11.1.6]. When the catalase activity of liver peroxisomes was irreversibly inhibited by administration of 3-amino-1,2,4-triazole (amino-triazole), the biosynthesis of bile acids was suppressed to about one-third, and the serum cholesterol level was increased. However, the bile acid components of the bile obtained from aminotriazole-treated rats were not essentially different from those of control rats, and no accumulation of intermediates of bile acid synthesis was found in this experiment. Peroxisomal FAOS activity of the liver from amino-triazole-treated rats was considerably lower than that of control liver. The above results indicate that liver peroxisomes play a role in the biosynthesis of bile acids in vivo.

Biosynthesis of Long-Chain Alcohols by Developing and Regenerating Rat Sciatic Nerve

Abstract: Cell-free preparations of rat sciatic nerve were found to catalyze the reduction of fatty acid to alcohol in the presence of NADPH as reducing cofactor. The reductase was membrane-bound and associated primarily with the microsomal fraction. When fatty acid was the substrate, ATP, coenzyme A (CoA), and Mg2+ were required, indicating the formation of acyl CoA prior to reduction. When acyl CoA was used as substrate, the presence of albumin was required to inhibit acyl CoA hydro-lase activity. Fatty acid reductase activity was highest with palmitic and stearic acids, and somewhat lower with lauric and myristic acids. It was inhibited by sulfhydryl reagents, indicating the participation of thiol groups in the reduction. Only traces of long-chain aldehyde could be detected or trapped as semicarbazone. Fatty acid reductase activity in rat sciatic nerve was highest between the second and tenth days after birth and decreased substantially thereafter. Microsomal preparations of sciatic nerve from 10-day-old rats exhibited about four times higher fatty acid reductase activity than brain or spinal cord microsomes from the same animals. Wallerian degeneration and regeneration of adult rat sciatic nerve resulted in enhanced fatty acid reductase activity, which reached a maximum at about 12 days after crush injury.

Biochemical derangements in ischemic myocardium: the role of carnitine.

Abstract: The most important biochemical derangements in ischemic myocardium are the decrease of energy rich phosphates (ATP and phosphocreatine) and intracellular acidosis, both of which contribute to a rapid loss of the contractile function. How and to which extent the alterations of carbohydrate and lipid metabolism are involved in these derangements is briefly discussed. In conditions of oxygen restriction the synchronism between the cytosolic and mitochondrial phase of carbohydrate metabolism is disrupted and beta-oxidation of long chain fatty acids is prevented. Consequently less ATP and more lactate is produced and fatty acids accumulate together with their activation products, acyl CoA in particular. In ischemia free carnitine is also decreased and the carnitine dependent functions (acyl transfer across mitochondrial membrane and pyruvate and alpha ketoglutarate dehydrogenase stimulation) impaired. The meaning of the altered carnitine dependent functions is considered together with the possible (demonstrated and supposed) metabolic effects of carnitine administration in cardiac ischemia.