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H Brunengraber

Publications and source records attributed to H Brunengraber.

106 records · Page 6Linked to original sources

(R)-mevalonate excretion in human and rat urines.

(R)-Mevalonate was identified by radioenzymatic assay in human and rat urines. This was confirmed by spectrophotometric enzymatic assay of an ether extract of human urine. The average excretion rate of (R)-mevalonate in humans was 1.7 mumol/24 hr which corresponds to 29% of the glomerular filtration rate. In anesthetized rats the average rate of (R)-mevalonate excretion was 350 pmol/min, corresponding to 44% of the glomerular filtration rate. These rates were not affected by the sex of the subjects or animals. After bilateral nephrectomy, the concentration of (R)-mevalonate in rat serum increased within 2 hr to a new level that was 5 times that of sham-operated controls. Nephrectomized rats showed a decrease in their tolerance to an intravenous load of mevalonate. These data show that (R)-mevalonate is normally excreted in the urine of humans and rats. Urinary excretion of (R)-mevalonate should therefore be taken into account in in vivo studies on the metabolism of this compound.

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Uptake of free choline by isolated perfused rat liver.

The uptake of free choline by isolated perfused rat liver was characterized. A saturable uptake mechanism [Ka = 0.17 +/- 0.07 mM (SD); Vmax = 0.84 +/- 0.16 mumol/min X g dry weight] and a nonsaturable mechanism (through which uptake is proportional to choline concentration in the perfusate) were identified. Most of the choline transported into hepatocytes was converted to betaine, phosphorylcholine, or lecithin. Free choline also accumulated within the intracellular space, suggesting that choline oxidase activity does not always limit choline's uptake by the liver.

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Fatty acid, 3-beta-hydroxysterol, and ketone synthesis in the perfused rat liver. Effects of (--)-hydroxycitrate and oleate.

The effects of oleate and hydroxycitrate on the rate of long-chain fatty acid and 3-beta-hydroxysterol synthesis were measured in perfused rat livers. Metabolite measurements show that in livers from fed animals inhibition of fatty acid synthesis by oleate or hydroxycitrate is associated with an increase in the tissue content of glucose 6-phosphate and fructose 6-phosphate, and a diminution in glycolytic intermediates from fructose diphosphate to phosphoenolpyruvate. Oleate also causes an increase in the tissue content of long-chain fatty acyl-CoA and citrate. The increase in long-chain fatty acyl-CoA is larger in livers from starved as compared to fed rats, while the increase in citrate is larger in livers from fed as compared to starved rats. However, the increase in the citrate content of livers from fed rats occurs in a range where it causes no further activation of acetyl-CoA carboxylase in vitro. Ketogenesis by livers from fed rats perfused without free fatty acids is strongly inhibited by hydroxycitrate. However, ketogenesis is not inhibited by hydroxycitrate when livers from starved rats are perfused with oleate, and ketogenesis is increased somewhat by hydroxycitrate when livers from fed rats are perfused with oleate. These results are interpreted in terms of an extramitochondrial pathway of ketogenesis which operates in carbohydrate-fed animals. The intramitochondrial pathway predominates in starved animals, or when the concentration of fatty acids is high, or both. Other interpretations, which cannot be ruled out at present, are also considered.

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Ultrastructure and intercellular vacuolization of isolated perfused and control rat testes.

Isolated rat testes perfused in closed circuit with albuminated Krebs-Ringer bicarbonate buffer were examined by light and electron microscopic techniques in order to assess the structural integrity of the model. The extent of intercellular vacuolization in perfused testes was similar to that of control testes that had been prepared for electron microscopy by routine methods of perfusion fixation. The isolated perfused testes exhibit excellent preservation at the light and electron microscope level. The results indicate that albuminated Krebs-Ringer bicarbonate buffer is an excellent perfusate for in vitro studies of the isolated rat testis. This model of perfused testis can be used to study the early pathology of the effects of toxic compounds on the microscopic anatomy of the male gonad.

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