Showing papers on "Acyl-CoA published in 1983"

Altered coenzyme A and carnitine metabolism in pressure-overload hypertrophied hearts

Abstract: Changes in the total content and acylation state of coenzyme A (CoA) and carnitine in the heart result in alterations in fatty acid metabolism that may be associated with ventricular dysfunction. The present study was undertaken to determine whether abnormal myocardial CoA and carnitine metabolism occur in pressure-overload hypertrophy and congestive heart failure. Right ventricular hypertrophy was induced in cats by pulmonary artery (PA) banding. Total tissue CoA was reduced by 50% in the hypertrophied right ventricle and 25% in the nonhypertrophied left ventricle of PA-banded cats in the presence or absence of heart failure. No alterations were observed in long-chain fatty acyl CoA levels in either ventricle of PA-banded cats. In addition, a 20% reduction in total CoA was also observed in hypertrophied hearts of rats subjected to aortic banding. Although the CoA content was reduced in hypertrophied cat hearts, myocardial tissue levels of its precursor, pantothenic acid, were unaltered. Total tissue carnitine and long-chain fatty acyl-carnitine levels were unchanged in both ventricles of PA-banded cats; however, total carnitine was reduced by 25% in hypertrophied rat hearts. This study establishes a marked reduction in myocardial CoA content in pressure-overload hypertrophy.

Computer simulation of metabolism in palmitate-perfused rat heart. I. Palmitate oxidation

Abstract: A computer model of the fatty acid oxidation pathway in perfused rat heart was constructed. It includes uptake, activation, and β-oxidation of fatty acids, triglyceride synthesis and hydrolysis, and carnitine-dependent transport of acyl groups across the mitochondrial membrane under pseudosteady state conditions. Fatty acid utilization may be limited by β-oxidation in hypoxia or ischemia but probably not in aerobic conditions. Nonesterified fatty acids bound to proteins are found to be metabolically available. The model predicts that stearate, but not palmitate, can support the highest observed respiration rate for perfused rat heart without supplementation by other substrates. Fatty acids are preferentially oxidized rather than being stored as triglycerides because the cystosolic acyl CoA level is lower than the Km for triglyceride synthesis. It is suggested that feedback inhibition of triglyceride lipase regulates utilization of triglycerides as fuel in aerobic hearts.

Biochemistry of unsaturated fatty acid isomers

Abstract: Recognition that catalytic hydrogenation changes the configuration and position of double bonds and alters the physical properties of unsaturated fats prompted numerous early investigations on the bio-chemical effects of ldtrans isomers.” Recent research has provided data on positional isomer metabolism. Some aspects of fatty acid isomer metabolism are now reasonably well understood, but other issues are not resolved. Human and animal data have provided good evidence that isomers in partially hydrogenated oils are well adsorbed and incorporated into all organs and tissues. Analyses of human tissues also indicate that hydrogenated oils are the major source of fatty acid isomers in the US diet. Tissue composition data combined with isolated enzyme studies and isotope tracer experiments with whole organisms show unquestionably that structural differences between various fatty acid isomers influence specific biochemical transformations. Examples are differences in the reaction rates and/ or specificities of acyl transferase, lipase, desaturase and cholesteryl esterase/hydrolase for various positional fatty acid isomers. Isolated microsomes and mitochondria also have been used to identify dif-ferences in acyl CoA activation, oxidation, and elongation of posi-tional isomers. In addition, isotope tracer experiments show that preferential metabolism of individual positional isomers occurs in vivo. In vivo studies with hydrogenated vegetable oil diets containing adequate levels of linoleic acid produced no obvious physiological changes. Experiments with specific polyunsaturated isomers have produced changes in blood cell properties, pulmonary weight, lino-leic acid requirements and tissue lipid composition. These changes may be related to a number of factors such as membrane fluidity and permeability, cell function, synthesis of arachidonic acid, homo-gamma-linoleic acid or prostaglandins. Whether differences in the biochemistry of fatty acid isomers are desirable or undesirable and whether these differences contribute to long-term or subtle effects important to the etiology of atherosclerosis and cancer are not resolved.

The synthesis of short- and long-chain acylarnitine by etio-chloroplasts of greening barley leaves.

Abstract: Etio-chloroplasts of barley, purified on sucrose density gradients were shown to possess carnitine long-chain acyltransferase (carnitine palmitoyltransferase, EC 2.3.1.21) activity and carnitine short-chain acyltransferase (carnitine acetyltransferase EC 2.3.1.7) activity. These enzymes may play a role in the transport of acyl groups as acylcarnitines through the membrane barrier of barley etio-chloroplasts and also 'or alternatively' may spare CoA by transferring short- and long-chain acyl groups from short-and long-chain acyl CoA to carnitine.

Localization of carnitine acyltransferases and acyl-CoA beta-oxidation enzymes in small intestinal microperoxisomes (peroxisomes) of normal and clofibrate treated mice.

Abstract: Dietary clofibrate for 21 days induced a rise in the specific activities of crotonase, acyl-CoA oxidase and carnitine acetyltransferase in a crude particulate fraction from mouse small intestinal mucosa. Subcellular fractionation of post-nuclear supernatant prepared from mucosal homogenates of normal and clofibrate treated animals allowed substantial separation of peroxisomes from contaminating organelles. Analysis of fractions demonstrated that intestinal peroxisomes contain acyl-CoA oxidase, crotonase, beta-hydroxyacyl-CoA dehydrogenase and carnitine acyltransferase activities. It is concluded that intestinal peroxisomes are equipped to engage in fatty acid oxidation.

Effects of L-carnitine on tissue levels of free fatty acid, acyl CoA, and acylcarnitine in ischemic heart.

Abstract: In order to evaluate the protective effects of L-carnitine on ischemic myocardium, its effects on tissue levels of free fatty acid (FFA), acyl CoA, acyl carnitine, and adenosine triphosphate (ATP) were studied in ischemic dog hearts. Myocardial ischemia was induced by the ligation of left anterior descending coronary artery for 15 min. L-Carnitine (100 mg/kg) was administered intravenously prior to coronary ligation. In ischemic myocardium, tissue levels of free carnitine and ATP decreased, whereas long-chain acyl carnitine, long-chain acyl CoA, and FFA increased. Pretreatment of L-carnitine prevented the decrease in free carnitine and ATP and the increase in long-chain acyl carnitine and long-chain acyl CoA. A positive correlation was observed between ATP and free carnitine. On the other hand, a negative correlation was observed not only between ATP and the ratio of long-chain acyl CoA to free carnitine but also between ATP and the ratio of long-chain acyl carnitine to free carnitine. These results suggest that L-carnitine has protective effects on ischemic myocardium, probably by preventing the accumulation of long-chain acyl carnitine and long chain acyl CoA.

β-oxidation of C-6-C-10 fatty acids in rat liver homogenates measured by selected ion monitoring: effects of cyanide and clofibrate

Abstract: The beta-oxidation of C-6-C-10-fatty acids/acyl CoA/acylcarnitines in whole rat liver homogenates was determined by specific and simultaneous measurements of the C-6-C-10-fatty acids, i.e. hexanoic, octanoic and decanoic acids, in hydrolysed homogenates in relation to time in assays incubated with the above-mentioned substrates. Measurements were performed by a combined gas chromatographic mass spectrometric technique, i.e. selected ion monitoring. The rate of beta-oxidation of the C-6-C-10-fatty acids/acyl CoA/acylcarnitines were registered as the consumption rate of the added substrate. The conversion to the C-2-shortened beta-oxidation products was illustrated simultaneously. The rate of beta-oxidation of C-6-C-10-fatty acids was several times higher in homogenates from clofibrate-treated rats than in control rats, both in the presence and absence of 2.0 mmol l-1 cyanide. Cyanide caused a minor but significant decrease in the beta-oxidation rate in both control and clofibrate-treated rats. No differences were found between the beta-oxidation of decanoic acid and decanoyl CoA in homogenates from clofibrate-treated rats, whereas the degree of beta-oxidation of DL-decanoylcarnitine was halved compared with decanoic acid and decanoyl CoA.

VII. Decrease in the Rate of Respiration in the Spermatozoa of the Sea Urchin, Hemicentrotus Pulcherrimus, Caused by Long Chain Fatty Acyl-CoA-induced Inhibition of the Movement. (sperm movement/carnitine/palmitoyl-CoA/sperm-egg interaction/sperm respiration)

Abstract: Spermatozoa of the sea urchin, Hemicentrotus pulcherrimus, showed marked decrease in respiration, and arrested movement after interaction with the fixed eggs. Immotile spermatozoa that had reacted with fixed eggs contained higher levels of long chain fatty acyl-CoAs than normal motile spermatozoa. On treatment with carnitine, the immotile spermatozoa became motile again and their intracellular concentrations of long chain fatty acyl-CoAs decreased. On incubation with anti-mycin A or CN− for 20 min, the motility of normal spermatozoa decreased gradually but their long chain fatty acyl-CoA content changed only slightly. The decrease in sperm motility in the latter case was probably due to decrease in the level of ATP, resulting from inhibition of respiration by antimycin A or CN−. The motility of spermatozoa extracted with Triton X-100 was restored by ATP and their movement was inhibited by long chain fatty acyl-CoAs, such as myristoly CoA and palmitoyl-CoA, but was not by short chain fatty acyl-CoAs, such as acetyl-CoA, propionyl CoA and butyryl-CoA. Na-palmitate, Na-myristate and CoA did not inhibit the reactivation of extracted spermatozoa by ATP.