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Biomedical subjects

S Segal

Publications and source records attributed to S Segal.

At least 649 records · Page 36Linked to original sources

Transport and metabolism of galactose in rat kidney cortex.

1. Analysis of transport of d-galactose was complicated by metabolism of the compound but appeared to have two components: a substrate-saturable component and a diffusion component. At low substrate concentration (<1mm) active transport was observed. Accumulation of galactose was largely independent of Na(+) concentration. The apparent K(m) for this component was 0.2mm. At substrate concentrations above 1mm the active transport system appeared saturated and further increases in substrate concentration resulted in a linear increase in the rate of galactose accumulation, but no concentration gradient was formed. 2. d-[1-(14)C]Galactose (2mm) was metabolized to (14)CO(2) by rat kidney-cortex slices incubated at 37 degrees C, at the rate of 68nmol/h per 100mg of tissue. 3. Intracellular components from such incubations were separated into a neutral fraction, the only major labelled component being galactose, and a phosphorylated fraction. 4. Phosphorylated metabolites found in galactose-incubated slices increased with increasing substrate concentration and achieved a limiting value of 0.42mm after 60min of incubation. 5. Galactose uptake was inhibited by anaerobiosis, dinitrophenol and phlorrhizin. 6. Methyl alpha-d-glucoside and d-glucose partially inhibited galactose uptake only at ratios of 100:1. 7. The presence of pyruvate did not decrease galactose metabolism although it did decrease production of (14)CO(2) from [1-(14)C]galactose. Gluconeogenesis occurred in the presence of pyruvate and (14)C from galactose was found in glucose. 8. Rat kidney-cortex slices metabolized 2mm-[1-(14)C]galactonate to (14)CO(2) at a rate of 20nmol/h per 100mg of tissue.

Anaerobiosis↗

Galactose toxicity in the chick: hyperosmolality.

Galactose-fed chicks have been found to develop severe hyperosmolar dehydration. Although biochemical abnormalities have been observed in the brain of the galactose-toxic chick, the observed physiologic alteration of serum osmolality could be the major factor responsible for the galactose toxicity syndrome in the chick.

Animals↗

Developmental aspects of uridine diphosphate galactose 4-epimerase in rat intestine.

Kinetic and developmental characteristics of rat intestinal UDP-galactose 4-epimerase activity have been examined. The enzyme in the adult rat had a V(max.) value 2-3 times higher than that of the newborn animal, but the K(m) values for the enzyme in the newborn and adult rat were the same (0.17mm). No differences in epimerase activity were found along the length of the jejuno-ileum of adult animals, but higher activity was detected in the lower portion of the villi and crypts. The specific activity of the enzyme in the newborn rat began to rise at about 17 days of age, reaching a peak at 29 days of age, and then became constant at adult values. Total epimerase activity in the newborn rat liver was 2-5 times higher than the total activity in the intestine, and total epimerase activity in the adult intestine was 3-4 times higher than the total activity in the liver. Cortisone injection did not enhance the increase of epimerase normally seen during development, but caused a decrease in activity of this enzyme in the jejunum in rats up to 17 days of age. After 17 days, cortisone treatment had no effect on epimerase activity.

Adrenalectomy↗

Separate transport systems for sugars and amino acids in developing rat kidney cortex.

The ability of renal cortical slices of newborn and young rats to accumulate a nonmetabolizable sugar, alpha-methylglucoside, is slight and does not reach adult capacity until 25 days of age. However, a rudimentary sugar transport system is present, as indicated by a further decrease in accumulation in the presence of phlorizin or absence of sodium ion.Amino acid uptake in immature kidney tissue is not deficient; on the contrary, the tissue took up and concentrated more glycine and lysine than adult tissue. Decreased amino acid efflux from the immature cells appears to be the explanation. Concentration dependence of amino acid uptake was the same in 5-day-old and adult tissue. These differences between the transport characteristics of a model sugar and representative amino acids during development indicate separate transport systems for the two types of substrate.

Amino Acids↗

Liver galactose-1-phosphate uridyl transferase: activity in normal and galactosemic subjects.

The kinetic characteristics of galactose-l-phosphate uridyl transferase have been determined in homogenates of human liver biopsies obtained from control subjects and in 50-fold purified enzyme preparations from liver obtained at autopsy. A standardized assay procedure employing linear kinetics was used to assess the enzyme activity in homogenates of liver biopsy specimens from five control subjects and four patients with congential galactosemia with demonstrated absence of the enzyme activity in red blood cells. Activity of control specimens ranged from 11.8 to 17.2 mmumoles of UDPgalactose formed per min mg of protein. Liver of two galactosemic patients, both Caucasian, possessed no detectable enzyme activity (less than 1-2% of normal). The tissue of two others, both Negro, who are known to be capable of metabolizing intravenously administered galactose, contained easily detectable enzyme at approximately 10% of the controls. No alternate enzymatic activity for formation of UDPgalactose was found in the liver of Negroes with galactosemia that was as active as the residual galactose-l-phosphate uridyl transferase. The data suggest that the residual liver enzyme activity accounts for the ability of Negroes with galactosemia to metabolize limited but significantly large quantities of galactose.

Adult↗

Effects of thyroid disease on glucose oxidative metabolism in man. A compartmental model analysis.

Glucose oxidation to CO(2) in man at the fasted, steady state has been investigated in normal, hypothyroid, patients by monitoring the specific activity of plasma glucose and expired CO(2) after intravenous injection of glucose-1-(14)C, glucose-6-(14)C, and sodium bicarbonate-(24)C in tracer amounts. Making certain stoichiometric assumptions about the oxidation of the C-1 and C-6 carbons of glucose to CO(2), the data are incorporated into a multicompartmental model describing the kinetics of plasma glucose, plasma bicarbonate, and the conversion of glucose to CO(2) by the hexose monophosphate pathway and all other series and parallel pathways which oxidize glucose carbon to CO(2) (EMP-TCA). This formulation separates the distribution kinetics of glucose and bicarbonate from the kinetics of glucose oxidation to CO(2). It allows the calculation of a minimal fraction (varphi(t)) of glucose irreversibly oxidized to CO(2) which is based entirely on the duration of the experimental data. This calculation is independent of the extrapolative implications of the model beyond the experimental interval and of the particular model chosen to fit the data. All modeling and data fitting were performed on a digital computer with the SAAM program. Based on a 300 min experiment the analysis suggests that in hypothyroidism there is a decrease in the rate of glucose metabolized irreversibly (rhoG). There is also a decrease in the minimal fraction (varphi(300)) which is completely oxidized to CO(2) by way of the EMP-TCA. rhoG and varphi(300) are 0.56 and 0.42 mmole/min respectively as compared to 0.89 and 0.50 mmole/min respectively in normals. However, the fraction of the C-1 of glucose metabolized irreversibly which undergoes oxidation to CO(2) by the hexose monophosphate pathway (Psi) is not different from normal (0.07 and 0.07 respectively). The hyperthyroid studies suggest that rhoG and varphi(300) are within the normal range (1.01 and 0.46 mmoles/min respectively as compared to 0.89 and 0.50 mmole/min respectively in normals). However, Psi is decreased to less than half the normal value (0.03 as compared to 0.07 in normals).

Adolescent↗