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Biomedical subjects

A L Shug

Publications and source records attributed to A L Shug.

At least 55 records · Page 3Linked to original sources
PubMed1981

The uptake of carnitine by slices of rat cerebral cortex.

The properties of carnitine transport were studied in rat brain slices. A rapid uptake system for carnitine was observed, with tissue-medium gradients of 38 +/- 3 for L-[14CH3]carnitine and 27 +/- 3 for D-[14CH3]carnitine after 180 min incubation at 37 degrees C in 0.64 mM substrate. Uptake of L- and D-carnitine showed saturability. The estimated values of Km for L- and D-carnitine were 2.85 mM and 10.0 mM, respectively; but values of Vmax (1 mumol/min/ml intracellular fluid) were the same for the two isomers. The transport system showed stereospecificity for L-carnitine. Carnitine uptake was inhibited by structurally related compounds with a four-carbon backbone containing a terminal carboxyl group. L-Carnitine uptake was competitively inhibited by gamma-butyrobetaine (Ki = 3.22 mM), acetylcarnitine (Ki = 6.36 mM), and gamma-aminobutyric acid (Ki = 0.63 mM). The data suggest that carnitine and gamma-aminobutyric acid interact at a common carrier site. Transport was not significantly reduced by choline or lysine. Carnitine uptake was inhibited by an N2 atmosphere, 2,4-dinitrophenol, carbonylcyanide-N-chlorophenylhydrazone, potassium cyanide, n-ethylmaleimide, and ouabain. Transport was abolished by low temperature (4 degrees C) and absence of glucose from the medium. Carnitine uptake was Na+-dependent, but did not require K4+ or Ca2+.

Animals↗
PubMed1980

Systemic carnitine deficiency--a treatable inherited lipid-storage disease presenting as Reye's syndrome.

A 3 1/2-year-old boy presented at three months of age with an acute episode of lethargy, somnolence, hypoglycemia, hepatomegaly, and cardiomegaly, which responded poorly to restoration of the blood sugar level to normal. The absence of ketonuria during subsequent episodes of severe hypoglycemia prompted a search for a defect in fatty acid oxidation. Plasma carnitine (2.0 to 5.0 mumol per liter), muscle carnitine (0.01 to 0.02 mumol per gram, wet weight) and liver carnitine (0.021 to 0.065 mumol per gram, wet weight) were all less than 5 per cent of the normal mean. During a 36-hour fast, ketones were barely detectable. Prolonged treatment with oral carnitine over a six-month period resulted in increased muscle strength, a dramatic reduction in cardiac size, relief of cardiomyopathy, partial repletion of carnitine levels in plasma and muscle, and complete repletion in the liver. Systemic carnitine deficiency is an easily treatable cause of recurrent Reye's-like syndrome. Its diagnosis requires measurement of carnitine levels.

Carnitine↗
PubMed1980

Properties of carnitine transport in rat kidney cortex slices.

The properties of carnitine transport were studied in rat kidney cortex slices. Tissue:medium concentration gradients of 7.9 for L-[methyl-14C]carnitine were attained after 60-min incubation at 37 degrees C in 40 microM substrate. L- and D-carnitine uptake showed saturability. The concentration curves appeared to consist of (1) a high-affinity component, and (2) a lower affinity site. When corrected for the latter components, the estimated Km for L-carnitine was 90 microM and V = 22 nmol/min per ml intracellular fluid; for D-carnitine, Km = 166 microM and V = 15 nmol/min per ml intracellular fluid. The system was stereospecific for L-carnitine. The uptake of L-carnitine was inhibited by (1) D-carnitine, gamma-butyrobetaine, and (2) acetyl-L-carnitine. gamma-Butyrobetaine and acetyl-L-carnitine were competitive inhibitors of L-carnitine uptake. Carnitine transport was not significantly reduced by choline, betaine, lysine or gamma-aminobutyric acid. Carnitine uptake was inhibited by 2,4-dinitrophenol, carbonyl cyanide m-chlorophenyl-hydrazone, N2 atmosphere, KCN, N -ethylmaleimide, low temperature (4 degrees C) and ouabain. Complete replacement of Na+ in the medium by Li+ reduced L- and D-carnitine uptake by 75 and 60%, respectively. Complete replacement of K+ or Ca2+ in the medium also significantly reduces carnitien uptake. Two roles for the carnitine transport system in kidney are proposed: (1) a renal tubule reabsorption system for the steady-state maintenance of plasma carnitine; and (2) maintenance of normal carnitine levels in kidney cells, which is required for fatty acid oxidation.

Acetylcarnitine↗
PubMed1979

Improved pacing tolerance of the ischemic human myocardium after administration of carnitine.

The possibility that DL-carnitine has a protective effect during myocardial ischemia was evaluated by performing two rapid coronary sinus pacing studies 15 minutes apart in 21 patients with coronary artery disease. Eleven patients received DL-carnitine (20 or 40 mg/kg) before the second pacing study. The treated group had a significant increase in mean heart rate (12.5 beats/min, P less than 0.001), pressure-rate product (1,912 units, P less than 0.01) and pacing duration (3.2 minutes, P less than 0.001) after the administration of carnitine. The treated group also had improvements in percent myocardial lactate extraction (8.8 percent increase, P less than 0.001) and left ventricular end-diastolic pressure (a decrease of 5.3 mm Hg, P less than 0.05). There was significantly less S-T segment depression during the second pacing period in both the untreated and treated groups. The results of this study suggest that in ischemic human hearts with reasonably well preserved left ventricular function, DL-carnitine may improve the tolerance for stress associated with an increase in heart rate and pressure-rate product.

Carbon Dioxide↗
PubMed1979

Pharmacokinetics of l-carnitine in man following intravenous infusion of dl-carnitine.

The pharmacokinetics of l-carnitine were studied in adult male patients following intravenous infusion of dl-carnitine hydrochloride-L-Carnitine appears to distribute into a rapidly perfused and then a more slowly perfused body space following administration. The overall apparent distribution volume Vd (ss) is consistent with extracellular body water. Serum levels of l-carnitine, from two different dose levels were adequately described by a two-compartment model. 80% of the administered dose was recovered in 24 hour post dose urine.

Adult↗
PubMed1979

Control of carnitine-related metabolism during myocardial ischemia.

Induction of ischemia in the open-chest dog or isolated rat heart caused a series of critical changes in carnitine-related metabolism. As a result of these metabolic changes, the LCACA/carnitine ratio rapidly increased which, in turn, may have reduced the activity of mitochondrial ANT and a number of other enzyme systems necessary for normal heart function. Carnitine administration apparently reversed these carnitine-linked metabolic changes and protected the ischemic myocardium. Possible mechanisms for the protective action of carnitine were discussed.

Aerobiosis↗
PubMed1976

Ultrastructural and physiological changes induced by atractylate in the canine myocardium.

The myocardial cellular response to the cardiac glycoside atractylate, a known inhibitor of mitochondrial adenine nucleotide translocation, was examined physiologically, morphologically, and morphometrically in eight dogs. An isolated in situ segment of left ventricular tissue was employed in these experiments to eliminate collateral flow and the potential for large sampling error. It was found that atractylate infusion rapidly induced physiological and morphological changes suggestive of a loss of membrane regulation of ion flux in the arteriole, capillary endothelium, and myocardial cell. Also mitochondrial changes suggestive of adenine nucleotide translocase inhibition were observed. As these responses are similar to those induced by acute myocardial ischaemia, it is suggested that ischaemia and atractylate induce cell injury by similar mechanisms.

Animals↗
PubMed1976

Control of energy production in myocardial ischemia.

Long chain fatty acyl-CoA esters are potent in vitro and in vivo inhibitors of adenine nucleotide translocation in heart mitochondria. Within a short time following production of myocardial ischemia, the dog heart exhibits an increased concentration of long chain acyl-CoA esters associated with a decrease in adenine nucleotide translocase activity. In contrast to liver, the tricarboxylate carrier system for citrate and phosphoenolpyruvate is rather low in heart mitochondria. Phosphoenolpyruvate-stimulated calcium egress from heart mitochondria may, therefore, result from transport of this anion on the adenine nucleotide translocase. During myocardial ischemia effective modulation of these metabolite trasnport systems are disrupted by accumulation of long chain acyl-CoA esters which leads to a decrease in the overall energy charge of the cell.

Animals↗