Otto Z. Sellinger

The inhibition in vivo of cerebral glutamine synthetase and glutamine transferase by the convulsant methionine sulfoximine

Abstract Evidence is presented for an in vivo interaction of the convulsant agent methionine sulfoximine (MSO) with glutamine synthetase (GS) and glutamine transferase of rat cerebral cortex. Unlike the in vitro interaction of MSO with GS, the in vivo effects of the drug on this enzyme activity were irreversible, as judged by the recovery of normal enzyme maximal velocity upon in vitro incubation in the presence of excess substrate (glutamate or ATP). Conversely, identity of the in vitro and in vivo effects of the drug on glutamine transferase was noted, since the inhibitory effect of MSO could be readily reversed at high in vitro concentrations of glutamine under both conditions.

Studies in vitro and in vivo of the effects of chlorpromazine on rat liver lysosomes

Abstract Evidence is presented demonstrating a stabilization of the rat liver lysosomal membrane by chlorpromazine both in vivo and in vitro . The lysosomal membrane is labilized in vitro by various incubation manipulations and in vivo by injection of vitamin A or Escherichia coli endotoxin. These data bear implications for some previously advanced hypotheses concerning the phenothiazine mode of action and may explain the protective effect of chlorpromazine in certain shock states.

THE METABOLISM OF LACTALDEHYDE. VII. THE OXIDATION OF D-LACTALDEHYDE IN RAT LIVER.

Abstract The preferential oxidation of the d -isomer of lactaldehyde by a partially purified enzyme obtained from rat liver and also found to occur in rat skeletal muscle, brain, lung, kidney, spleen and heart is reported. The oxidation is nicotinamide-adenine-dinucleotide dependent and fails with nicotinamide-adenine dinucleotide phosphate. Methylglyoxal and not lactate was demonstrated as the reaction product. The reaction was readily reversible. From the obtained evidence, the participation of free -SH groups and an ordered addition of substrates are suggested as requirements for catalytic function.

The metabolism of acetol phosphate. I. Synthesis, properties and enzymic reduction.

Abstract The chemical synthesis of acetol phosphate and its chromatographic separation from a number of closely related three-carbon phosphates are reported. Using a rabbit muscle α-glycerophosphate dehydrogenase preparation, Km values for dihydroxyacetone phosphate, DPNH, DL -α-glycerophosphate, acetol phosphate and DL - I ,2-propanediol- I -phosphate were obtained. The affinity ratio dihydroxyacetone phosphate to acetol phosphate was estimated to be 330. Possible mechanisms for the alkaline and acid hydrolysis of the phosphate group in α-keto phosphate esters of the type RCOCH2OPO3H2 were discussed. The possibility that a specific enzyme, catalyzing the reduction of acetol phosphate is pointed out.

The induction of mitochondrial α-glycerophosphate dehydrogenase by thyroid hormone: Effects of adrenalectomy, thyroidectomy and cortisone administration

Abstract In adrenalectomized animals, a single administration of triiodothyronine triggers off an induction of hepatic mitochondrial α-glycerophosphate dehydrogenase ( L -glycero-3-phosphate: cytochrome c oxidoreductase, EC 1.1.99.5) comparable to that seen in intact animals. A qualitatively similar effect is observed in adrenalectomized animals supplemented with cortisone but, in this case, the extent of the induction by triiodothyronine is diminished. The administration of cortisone counteracts the stimulatory effect of adrenalectomy per se on α-glycerophosphate dehydrogenase levels but has no effect on the basal levels of this enzyme activity in intact animals. Adrenalectomy has a more pronounced stimulatory effect upon α-glycerophosphate dehydrogenase levels of thyroidectomized than of intact animals. Puromycin and actinomycin D inhibit the induction of α-glycerophosphate dehydrogenase by triiodothyronine in thyroidectomized animals as effectively as in intact animals.

THE METABOLISM OF LACTALDEHYDE. VI. THE REDUCTION OF D- AND L-LACTALDEHYDE IN RAT LIVER.

Abstract The partial purification from rat liver of a NAD-dependent enzymic activity, utilizing d -and l -lactaldehyde equally well, is described. 1,2-propanediol was identified as the product of lactaldehyde reduction. The described activity is shown to differ from enzymic activities heretofore reported to utilize lactaldehyde in other tissues.

ADENOSINE TRIPHOSPHATE CREATINE PHOSPHOTRANSFERASE OF RAT CEREBRAL CORTEX: EVIDENCE FOR A BIMODAL SUBCELLULAR LOCALIZATION*

—(1) ATP: creatine phosphotransferase of rat cerebral cortex is soluble to the extent of 57 per cent when the tissue is homogenized in 0.25 M‐sucrose and 80 per cent when distilled water is used for tissue dispersion. Among particulate fractions, the crude mitochondria] fraction contains the highest percentage of enzyme activity.

Induction of Mitochondrial α-Glycerophosphate Dehydrogenase by Thyroid Stimulating Hormone and Thyroid Hormone Analogues.

Summary The level of mitochondrial L-alpha-glycerophosphate dehydrogenase of rat liver is greatly decreased after hypophysectomy. The lowered enzyme level in these animals was rapidly restored after administration of a single dose of L-triiodothyronine. Thyroid-stimulating hormone given to hypophysectomized rats, gradually increased the enzyme activity and this response depended on both the dosage and the duration of treatment. A number of iodine-containing compounds were used to evaluate the chemical specificity of structure of inducing molecules. The results showed a good correlation between the inducing ability of these analogues and its hormonal activity. The reported observations support the idea that mitochondrial L-alpha-glycerophosphate dehydrogenase activity is controlled by the thyroid hormone. The “admixture test” failed to show the presence of an activator or the absence of an inhibitor in the mitochondrial preparation obtained from L-triiodothyronine-treated animals. The present observations further support the previous suggestion that the increase of mitochondrial L-alpha-glycerophosphate dehydrogenase activity after the administration of thyroid hormone may result from acceleration of enzyme synthesis even when stimulated by physiological amounts of the hormone.