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Biomedical subjects

A L Greenbaum

Publications and source records attributed to A L Greenbaum.

At least 37 records · Page 2Linked to original sources
PubMed1986

Concentration of phosphoribosyl pyrophosphate in the kidney during development and in experimental diabetic hypertrophy.

The effect of developmental growth on the kidney content of phosphoribosyl pyrophosphate PPRibP was studied in rats at ages between the foetal animal and up to 100 days of age. In addition, the effect of short-term diabetes (up to 14 days) on the renal content of PPRibP was studied in immature rats and in adults aged approx. 60 days. The developmental pattern of PPRibP is such that the PPRibP content is lowest in the young rat and increases as the rate of kidney growth slows. In the adult rat, the early kidney hypertrophy of diabetes is accompanied by a fall in PPRibP content and, again, the PPRibP content returns to normal as the rate of kidney hypertrophy diminishes. Induction of diabetes in the immature rat causes a lesser degree of kidney hypertrophy and also a smaller depression of renal PPRibP content. The activity of PPRibP synthetase (EC 2.7.6.1) is not significantly affected by age or diabetes. The changes in PPRibP content are discussed in relation to the generation of ribose 5-phosphate by the pentose phosphate pathway and the utilization of PPRibP for nucleotide synthesis via the 'de novo' and salvage pathways.

Age Factors↗
PubMed1985

The insulin-mimetic action of Mn2+: involvement of cyclic nucleotides and insulin in the regulation of hepatic hexokinase and glucokinase.

Manganese causes a significant rise in hepatic glucokinase and hexokinase in 16-day-old suckling rats, and has an insulinomimetic effect in producing a precocious emergence of glucokinase (EC 2.7.1.2) and a rise in the low Km, hexokinases (EC 2.7.1.1) activities. These enzyme changes occur within 6 hr of manganese administration and there are accompanying increases in plasma insulin and hepatic cyclic GMP. That the effect of manganese is at a site other than, or in addition to, insulin secretion is suggested by the significant increases in glucokinase and hexokinase in 16-day-old streptozotocin-diabetic rats; in this group there is also an increase in hepatic cGMP similar in time scale to that of the normal-manganese-treated group. The effects of manganese and insulin were not additive. It is proposed that one site of action of manganese may be at the level of cyclic GMP systems. The results are also discussed in relation to the known action of manganese at the level of the protein phosphatases.

Animals↗
PubMed1984

Fructose 2,6-bisphosphate, sugar phosphates and adenine nucleotides in the regulation of glucose metabolism in the lactating rat mammary gland.

Fructose 2,6-bisphosphate is present in the rat mammary gland, rising from a value of 1.4 nmol/g in pregnancy to 4.3 nmol/g tissue at 14 days lactation; the equivalent values calculated/ml intracellular water are 5.2 and 11.6 nmol, respectively. The tissue content of fructose 6-phosphate, fructose 1,6-bisphosphate, ATP and phosphoenolpyruvate remain relatively constant in the transition from pregnancy to the height of lactation. The changes in AMP, cyclic AMP, and citrate content of the mammary gland during lactation are such as to promote an increase in fructose 2,6-bisphosphate formation and flux through phosphofructokinase.

Adenosine Monophosphate↗
PubMed1983

Alternative pathways of glucose utilization in brain: changes in the pattern of glucose utilization and of the response of the pentose phosphate pathway to 5-hydroxytryptamine during aging.

The oxidation of differentially labelled glucose, pyruvate and glutamate in brain slices from rats aged 20 days to 26 months has been studied and the partition of the glucose used into the glycolytic-tricarboxylic acid cycle pathway, the pentose phosphate pathway and the glutamate-GABA shunt has been calculated. Over the time range 4 to 26 months, there is an approximately 20% decrease in the production of CO2 via the glycolytic-tricarboxylic acid cycle route, as there is in the rate of glucose phosphorylation. The glutamate-GABA pathway falls by about 50% over this same time span. The broad activity of the pentose phosphate pathway falls rapidly and cannot be detected in the brains of rats aged 18 months or more, whereas the fully stimulated pathway, i.e. in the presence of the artificial electron acceptor phenazine methosulphate, declines only marginally over this period, falling sharply only after 23 months. The pentose phosphate pathway is stimulated by the presence of 5-hydroxytryptamine and this stimulation appears to increase with age.

Aging↗
PubMed1982

The functional significance of the pentose phosphate pathway in synaptosomes: protection against peroxidative damage by catecholamines and oxidants.

Catecholamines added in vitro in rat brain synaptosomes activate the decarboxylation of glucose radioactively labelled on carbon 1, suggesting an effective activation of the pentose phosphate pathway. Stimulation also occurred with phenazine methosulphate, reduced glutathione and hydrogen peroxide. The activation of the pentose phosphate pathway by 5-hydroxytryptamine, noradrenaline and dopamine is ascribed to the activation of monoamine oxidase, producing both the respective biogenic aldehyde and hydrogen peroxide. Evidence is presented that the further metabolism of the aldehyde by aldehyde reductase and the removal of hydrogen peroxide by glutathione peroxidase both release the limitation of NADP+ availability for the pentose phosphate pathway by leading to the oxidation of NADPH. The relevance of the maintenance of reduced NADP+ on brain is discussed in relation to the metabolism of glutathione and to lipid peroxidation.

Aldehyde Oxidoreductases↗
PubMed1982

Age-related changes in enzymes of rat brain. III. Hydrogen-transfer systems in relation to the disposition of acetyl groups in the brain.

The flux of glucose in the pathways of acetyl group formation and disposal and the activities of a range of enzymes related to these processes have been measured in the brains of rats aged between 1 day and 24 months. The pattern of enzyme change is such that those systems involved in hydrogen transfer appear to increase disproportionately, relative to the glycolytic flux in the aged brain. It is suggested that these increases are an essential corollary to the need for a maintained glycolytic flux in a tissue dependent upon glucose as a fuel and one in which alternative routes of NADH oxidation diminish with age.

Age Factors↗
PubMed1981

Alternative pathways of glucose utilization in brain; changes in the pattern of glucose utilization in brain resulting from treatment of rats with 6-aminonicotinamide.

The effect of 6-aminonicotinamide (6AN) treatment on the activities of alternative pathways of glucose metabolism in 20-day-old rat brain was evaluated by measurements of yields of 14CO2 from glucose labeled with 14C on carbons 1, 2, 3 + 4, or 6 and uniformly labeled glucose, and from the incorporation of 14C from specifically labeled glucose into lipids by brain slices from cerebral hemispheres and cerebellum. At the highest dose of 6AN used (35 mg/kg body weight) there was a significant decrease in the 14CO2 yields via the pentose phosphate pathway, the glycolytic route, tricarboxylic acid (TCA) cycle, and via the glutamate-gamma-aminobutyric acid pathway. Giving a graded series of doses (20-35 mg 6AN/kg body weight) revealed a hierarchy of responses in which the pentose phosphate pathway, lactate, glyceride-glycerol, and fatty acid formation were most sensitive, followed, in sequence, by the pyruvate dehydrogenase reaction, the glutamate-gamma-aminobutyrate route and, finally, the TCA cycle. The nature of the blocks in the various pathways was examined by the use of metabolite profiles.

6-Aminonicotinamide↗
PubMed1981

Age-related changes in enzymes of rat brain. 1. Enzymes of glycolysis, the pentose phosphate pathway and lipogenesis.

Measurements have been made of the activity of the enzymes of the glycolytic, pentose phosphate and lipogenic pathways and of some marker enzymes of the tricarboxylic acid cycle in brains of rats aged between 20 days and 24 months. In general, the activity of the most enzymes measured was unchanged by aging but exceptions to this were increases of hexokinase, glucose-6-phosphate dehydrogenase and 'malic enzyme' and decreases of ATP-citrate lyase, acetyl-CoA carboxylase and fatty acid synthetase. An exceptionally large (2-fold) increase in the activity of cytosolic glycerol 3-phosphate dehydrogenase was noted. These changes are considered in relation to the overall metabolic activity of the brain.

Aging↗
PubMed1981

Age-related changes in enzymes of rat brain. 2. Redox systems linked to NADP and glutathione.

Measurements have been made of the enzymes of glutathione metabolism and of NADPH generation in the brains of rats aged between 1 day and 24 months. The activity of glutathione peroxidase fell while that of glutathione reductase rose during the aging process. The four NADPH-generating systems each showed a different profile with respect to aging, the most marked changes occurring between 1 and 20 days. Subsequently, the systems remained close to, or above, the young adult value. The role of the glutathione-metabolising enzymes in controlling the H2O2 metabolism and suppressing peroxidative damage to the brain is discussed.

Aging↗
PubMed1981

Regulation of pathways of ornithine metabolism. Effects of thyroid hormone and diabetes on the activity of enzymes at the "ornithine crossroads' in rat liver.

There is a significant increase in four of the urea cycle enzymes in liver from hypothyroid rats, arginase alone showed an opposite trend; these changes are reversed by physiological doses of thyroxine; hyperthyroidism results in a significant decrease in ornithine transcarbamoylase activity. The pattern of change in thyroidectomized and alloxan-diabetic rats showed marked similarities in respect to urea cycle and ornithine-metabolizing enzymes which are discussed in the light of the common feature of hypoinsulinism of diabetes and depressed response to insulin in hypothyroidism. The profile of ornithine-metabolizing enzymes is consonant with the decreased protein synthesis and turnover in hypothyroidism.

Animals↗
PubMed1978

Adaptive responses of enzymes of carbohydrate and lipid metabolism to dietary alteration in genetically obese Zucker rats (fa/fa).

1. Measurements have been made of the activities of enzymes of the glycolytic route, the pentose phosphate pathway, the tricarboxylic acid cycle and lipogenesis in liver and adipose tissue from genetically obese (fa/fa) rats and their lean litter mates (fa/ --). The effect of food restriction for a period of three weeks on the enzyme profile of liver and adipose tissue of the obese rat was also studied. 2. The most striking increases in enzyme activity in livers from obese rats were: (a) among enzymes of lipogenesis; ATP-citrate lyase, acetyl-CoA carboxylase, fatty acid synthetase, malate dehydrogenase (decarboxylating) and cytoplasmic glycerolphosphate dehydrogenase; (b) within the pentose phosphate pathway; glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase; (c) within the glycolytic pathway; glucokinase, pyruvate kinase and lactate dehydrogenase. All of these enzymes showed a significant increase in activity on the basis of U/g liver and U/mg DNA. In adipose tissue all the enzymes of lipogenesis, of the glycolytic route, of the oxidative segment of the pentose phosphate pathway and of the tricarboxylic acid cycle were increased when expressed as U/2 fat pads or as U/mg DNA. 3. The restriction of the food intake of obese rats to that consumed by their lean litter mates for periods of three weeks did not produce the expected adaptive decrease in enzymes of lipogenesis; in adipose tissue, only ATP-citrate lyase and malate dehydrogenase (decarboxylating) showed a marked decrease; no significant change was found in adipose tissue or liver of the activities of acetyl-CoA carboxylase and fatty acid synthetase, when expressed on a cell basis (U/mg DNA). The non-oxidative enzymes of the pentose phosphate pathway and enzymes involved in glycerogenesis (pyruvate carboxylase, malate dehydrogenase and phosphoenolpyruvate carboxykinase) all increased in adipose tissue from limit-fed obese rats. 4. The rate of conversion of specifically labelled glucose to (14C)O2 and 14C-labelled lipid by pieces of adipose tissue and by liver slices was also measured. Insulin caused an increase in the conversion of (1-14C)glucose to (14C)O2 and 14C-labelled lipid in obese rats fed ad libitum, limit-fed rats and in their lean litter mates. 5. The results are discussed in relation to the raised insulin and hypothyroid state of the obese rat. The effect of this altered hormonal status on the activity of cyclic nucleotide phosphodiesterases and cellular levels of adenosine 3' :5'-monophosphate and guanosine 3' :5'-monophosphate and guanosine 3' :5'-monophosphate in relation to the obese syndrome is considered.

Adipose Tissue↗
PubMed1978

Regulation of mammary gland metabolism: pathways of glucose utilization, metabolite profile and hormone response of a modified mammary gland cell preparation.

1. A method for the preparation of isolated mammary gland cells of the rat is described. 2. The procedure involves disaggregation of the tissue in a collagenase-hyaluronidase mixture and subsequent purification of the heterogeneous population of cells by centrifugation in discontinuous Ficoll-400 gradients; the preparation takes 60 minutes. The yield of cells is approximately 14%. 3. The cells as prepared have high rates of metabolism and synthetic capacity and exhibit metabolic characteristics comparable to intact tissue. 4. Measurements of the content of metabolic intermediates show cells to have, and retain, outstandingly high levels of ATP and to have an energy charge close to 0.9. Levels of other intermediates approximate to those found in the intact tissue. The level of glycolytic intermediates below the triose phosphate stage indicate the highly aerobic state of the cells. 5. The pattern and scale of glucose utilization, measured using specifically labelled glucose incorporation into 14CO2 and 14C-labelled lipid production, approximates closely in isolated cells at 5 and 20 mM glucose and in tissue slices at 20 mM glucose concentration. Mammary gland slices incubated with 5 mM glucose have a considerably lower rate of metabolism. Isolated cells exhibit a higher proportionate rate of glucose utilization by way of the pentose phosphate pathway. 6. The isolated cells are hormone responsive. Insulin increases the oxidation of glucose by the pentose phosphate pathway and stimulates lipid synthesis. Addition of progesterone and cortisone in vitro (10 muM) leads to a marked and rapid decrease in the rate of glucose oxidation and conversion to lipid.

Adenine Nucleotides↗
PubMed1977

Aspects of carbohydrate metabolism in developing brain.

This review considers carbohydrate metabolism in the developing brain, in particular the proportion of glucose metabolized via the pentose phosphate pathway. Although small in amount, this fraction serves a vital rôle in some aspects of brain function. Evidence is presented that the pentose phosphate pathway subserves different functions as the developing brain progresses through the stages of growth and myelination to full neurological competence. The general aspects considered are the changing patterns of brain enzymes during development; the flux of glucose through the alternative pathways of glucose metabolism in the developing brain; the functional significance of the pentose phosphate pathway; and the regional and functional association of the pentose phosphate pathway activity and the detoxication of biogenic amínes.

Age Factors↗
PubMed1977

Changes in renal cyclic nucleotide content as a possible trigger to the initiation of compensatory renal hypertrophy in rats.

1. Cyclic adenosine 3', 5'-monophosphate (cyclic AMP) and cyclic guanosine 3', 5'-monophosphate (cyclic GMP) have been estimated in the kidneys of rats.2. Ten minutes after unilateral nephrectomy there was a threefold increase of cyclic GMP in the remaining kidney, which was accompanied by a moderate fall of cyclic AMP.3. The changes in cyclic nucleotides in the remaining kidney after unilateral nephrectomy were of short duration.4. When an anephric rat was cross-circulated with a normal litter-mate, there was an increase of cyclic GMP concentration in the kidneys of the latter, which reached its maximum 10 min after the establishment of the cross circulation.5. In experiments where one kidney of a litter-mate was transplanted to the neck of another rat, unilateral nephrectomy was not followed by changes of the level of cyclic nucleotides in either the transplanted or the remaining kidney. Bilateral nephrectomy, however, resulted in a marked increase of cyclic GMP in the transplanted kidney.6. The clamping of the blood vessels to one kidney for periods up to 10 min had the same effect as unilateral nephrectomy on the concentration of cyclic GMP in the remaining kidney. When the clamp was removed and the circulation restored, the concentrations of cyclic nucleotides returned to preoperative levels in both kidneys.

Animals↗
PubMed1977

Compensatory renal hypertrophy in hypophysectomized rats.

1. After hypophysectomy, both body and kidney weights fall, but at different rates. The rate at which the kidney decreases in weight is faster than that of the whole body.2. Seven days after unilateral nephrectomy, the dry weight of the remaining kidney of hypophysectomized rats, with the exception of rats which had been hypophysectomized for 2 days only, was always heavier than the kidney of control hypophysectomized rats of similar body weight.3. The difference between the dry weight of kidneys of unilaterally nephrectomized hypophysectomized and control hypophysectomized rats increased from 15% in early hypophysectomized (9 days) to about 35% in late hypophysectomized animals (23 days).4. The implantation of renal cortical cells from 2 day hypophysectomized rats into unilaterally nephrectomized control litter-mates inhibited compensatory renal hypertrophy in the latter. When a similar operation was made using kidney cells from animals which had been hypophysectomized for 23 days, there was no significant inhibition of compensatory renal hypertrophy.5. The renal contents of adenosine-3',5'-monophosphate (cyclic AMP) and of guanosine-3',5'-monophosphate (cyclic GMP) in rats hypophysectomized for 2 days were of the same order as those in normal rats, but were markedly lower in rats hypophysectomized for 23 days.6. In contrast to what had been observed in normal rats, in hypophysectomized (2 or 23 days) rats, unilateral nephrectomy did not affect significantly the levels of cyclic nucleotides in the remaining kidney.7. Cross-circulating anephric normal rats with 2 day hypophysectomized animals resulted in an increase of cyclic GMP content in their kidneys. The cross-circulation between anephric normal rats and 23 days hypophysectomized rats had no effect on the level of renal cyclic GMP of the latter.8. When rats hypophysectomized for either 2 or 23 days and which had been nephrectomized were cross-circulated with normal rats, there were no changes in the content of cyclic GMP in the kidneys of the latter.

Animals↗