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M L Halperin

Publications and source records attributed to M L Halperin.

At least 235 records · Page 13Linked to original sources
PubMed1975

Effect of 2-methylcitrate on citrate metabolism: implications for the management of patients with propionic acidemia and methylmalonic aciduria.

2-Methylcitrate was tested in vitro on enzymes which interact with citrate and isocitrate. It was found to inhibit citrate synthase, aconitase, the NAD+- and NADP+-linked isocitrate dehydrogenase. This inhibition was competitive in nature except in the case of aconitase, and the Ki for all the enzymes was in the range of 1.5-7.6 mM. Phosphofructokinase was also inhibited by 2-methylcitrate with 50% inhibition achieved at 1 mM. ATP-citrate lyase and acetyl-CoA carboxylase were not inhibited by this compound. 2-Methylcitrate was not a substrate for ATP-citrate lyase. Acetyl-CoA carboxylase was activated by 2-methylcitrate with a Ka of 2.8 mM. The apparent Km (3.3 mM) for 2-methylcitrate for the mitochondrial citrate transporter was about 10-fold higher than the apparent Km (0.26 mM) for citrate. The tricarboxylase carrier can also be inhibited by low concentrations (0.2 mM) of 2-methylcitrate when the concentration of citrate is close to the apparent Km. Accumulation of 2-methylcitrate inside the mitochondrion, therefore, might lead to inhibition of enzymes in the citric acid cycle and thereby contribute to the ketogenesis and hypoglycemia seen under these conditions.

Animals↗
PubMed1975

Insulin therapy in phenformin-associated lactic acidosis; a case report, biochemical considerations and review of the literature.

A patient with phenformin-associated lactic acidosis was treated with insulin and showed marked improvement coincident with the expected onset of action of the insulin administered. Relative insulin deficiency was demonstrated although several phenomena characteristic of phenformin-associated lactic acidosis obscured its reflection in the usual indices. From data presented and a review of the literature the following pathogenesis is proposed for the observed metabolic derangement. A background of relative insulin deficiency would permit enhanced pyruvate (and hence lactate) formation from protein sources. Insulin deficiency would also lead to inhibition of pyruvate dehydrogenase which slows pyruvate removal. Phenformin accumulation (cf impaired renal function) further reduces pyruvate removal by decreasing its conversion to glucose, but in addition alters the redox state. For the lactic acidosis which results, insulin administration may thus constitute specific therapy. Diabetes 24:28-35, January, 1975.

Acidosis↗
PubMed1974

Studies on the pathogenesis of type I (distal) renal tubular acidosis as revealed by the urinary PCO2 tensions.

This study was designed to investigate the pathogenesis of type I (distal) renal tubular acidosis. Urinary and blood Pco(2) tensions were determined when the pH of the urine was equal to or exceeded the corresponding blood pH. This provided an indication of net hydrogen ion secretion in the distal nephron. In 16 normal subjects, the Pco(2) of the urine exceeded blood values (U-B Pco(2)) by 32.7+/-3.1 mm Hg. In contrast, the urinary Pco(2) tensions in 10 patients with type I (distal) renal tubular acidosis were not significantly greater than blood values (U-B Pco(2) = 2.0+/-2.2 mm Hg). These results indicate that type I (distal) renal tubular acidosis is caused by failure of the cells of the distal nephron to secrete hydrogen ions rather than to gradient-limited hydrogen ion addition to the urine. This is suggested by the fact that urinary Pco(2) levels should be higher than blood Pco(2) levels when hydrogen ions are secreted into urine containing bicarbonate in the distal nephron and they were not in this study despite the presence of a favorable hydrogen ion gradient (tubular fluid pH exceeded blood pH).

Acidosis, Renal Tubular↗
PubMed1973

Effect of insulin on pyruvate metabolism in epididymal adipose tissue of the rat. Correlation of intracellular pyruvate contents and pyruvate dehydrogenase activity.

A method is described to measure the intracellular content of pyruvate and lactate in epididymal adipose tissue of the rat. The intracellular pyruvate concentration was approx. 330mum. Intracellular pyruvate contents and the rates of pyruvate output were increased when NNN'N'-tetramethyl-p-phenylenediamine was added, and decreased in the presence of alanine. Insulin addition caused an increase in intracellular pyruvate contents only at the earlier time-period studied (1.5min as against 20min). Pyruvate dehydrogenase activity was increased in adipose tissue incubated in vitro with insulin. This increase occurred subsequent to the rise in the intracellular pyruvate content induced by insulin addition. The possible physiological implications are discussed.

Adipose Tissue↗
PubMed1972

Effects of palmitoyl CoA on citrate and malate transport by rat liver mitochondria.

Palmitoyl CoA inhibited citrate transport from isolated rat liver mitochondria. Under conditions described, 50% inhibition was observed at about 6-8 nmol/mg of mitochondrial protein per ml. The percentage inhibition was inversely proportional to the concentration of the counter-transporting anion in the medium. Although comparable levels of palmitoyl CoA had little effect on malate exit on the dicarboxylate carrier, higher concentrations inhibited both citrate and malate transport. The specificity of the inhibition by palmitoyl CoA was investigated by examination of the effects on the tricarboxylate transport system of fatty acids, CoASH, acetyl CoA, palmitoylcarnitine, deoxycholate, and other molecules with surface active properties. None of the above compounds, at sublytic concentrations, inhibited citrate transport appreciably. The inhibition of citrate transport by low concentrations of palmitoyl CoA was rapid and could be prevented or partially reversed by addition of albumin.

Albumins↗
PubMed1971

Studies on the conversion of pyruvate into fatty acids in white adipose tissue. Effects of insulin, alloxan-diabetes and starvation.

The effect of insulin on the conversion of pyruvate into fatty acids in the presence and in the absence of glucose was studied in epididymal adipose tissue of the rat. 1. In adipose tissue from the normal rat, conversion of pyruvate into fatty acids is directly related to its concentration, the maximal rates occurring with 40mm- and the half-maximal rates with approx. 4mm-pyruvate. Insulin treatment did not greatly influence the maximal rates, but the half-maximal rates were at much lower pyruvate concentrations. This effect of insulin could be seen with physiological concentrations of this hormone (50-100muunits/ml). 2. In adipose tissue from acute-alloxan-diabetic and 36h-starved rats the conversion of pyruvate into fatty acids was almost zero until its concentration exceeded 3mm and then increased markedly as the concentration of pyruvate was increased. The lag phase of this S-shaped curve was decreased but not eliminated when insulin was present. This could account for the very low rates of glucose conversion into fatty acids in these metabolic states. Maximum rates of fatty acid synthesis were similar in the presence and in the absence of insulin, but only when 30-40mm-pyruvate was employed. Re-feeding of the starved rats or insulin treatment of the diabetic rats in vivo for several days restored these patterns to normal.

Adipose Tissue↗