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Biomedical subjects

M S Patel

Publications and source records attributed to M S Patel.

At least 181 records · Page 10Linked to original sources

Energy metabolism in feasting and fasting.

During feasting on a balanced carbohydrate, fat, and protein meal resting metabolic rate, body temperature and respiratory quotient all increase. The dietary components are utilized to replenish and augment glycogen and fat stores in the body. Excessive carbohydrate is also converted to lipid in the liver and stored along with the excessive lipids of dietary origin as triglycerides in adipose tissue, the major fuel storage depot. Amino acids in excess of those needed for protein synthesis are preferentially catabolized over glucose and fat for energy production. This occurs because there are no significant storage sites for amino acids or proteins, and the accumulation of nitrogenous compounds is ill tolerated. During fasting, adipose tissue, muscle, liver, and kidneys work in concert to supply, to convert, and to conserve fuels for the body. During the brief postabsorptive period, blood fuel homeostasis is maintained primarily by hepatic glycogenolysis and adipose tissue lipolysis. As fasting progresses, muscle proteolysis supplies glycogenic amino acids for heightened hepatic gluconeogenesis for a short period of time. After about three days of starvation, the metabolic profile is set to conserve protein and to supply greater quantities of alternate fuels. In particular, free fatty acids and ketone bodies are utilized to maintain energy needs. The ability of the kidney to conserve ketone bodies prevents the loss of large quantities of these valuable fuels in the urine. This delicate interplay among liver, muscle, kidney, and adipose tissue maintains blood fuel homeostasis and allows humans to survive caloric deprivation for extended periods.

Acid-Base Equilibrium↗

Age-dependent changes in the oxidative metabolism in rat brain.

The effects of aging on the oxidation of labeled glucose and 3-hydroxybutyrate and on several mitochondrial enzymes in rat brain were investigated. The oxidation of labeled glucose and labeled 3-hydroxybutyrate was diminished by about 40 and 35%, respectively, in cerebral cortex slices from 2-year-old rats compared to those from 3-mo-old animals. A significant reduction in the activities of 3-hydroxybutyrate dehydrogenase, 3-oxo acid CoA transferase, acetoacetyl CoA thiolase, and NAD-isocitrate dehydrogenase was observed in brains of 1- and 2-year-old rats compared to 3-mo-old animals. However, aging had no effect on the activities of citrate synthase and pyruvate carboxylase. These findings show that specific alterations occur in the activities of several mitochondrial enzymes in aging brain.

Aging↗

Lipogenesis from ketone bodies in rat brain. Evidence for conversion of acetoacetate into acetyl-coenzyme A in the cytosol.

The metabolism of acetoacetate via a proposed cytosolic pathway in brain of 1-week-old rats was investigated. (-)-Hydroxycitrate, an inhibitor of ATP citrate lyase, markedly inhibited the incorporation of carbon from labelled glucose and 3-hydroxybutyrate into cerebral lipids, but had no effect on the incorporation of labelled acetate and acetoacetate into brain lipids. Similarly, n-butylmalonate and benzene-1,2,3-tricarboxylate inhibited the incorporation of labelled 3-hydroxybutyrate but not of acetoacetate into cerebral lipids. These inhibitors had no effect on the oxidation to 14CO2 of the labelled substrates used. (-)-Hydroxycitrate decreased the incorporation of 3H from 3H2O into cerebral lipids by slices metabolizing either glucose or 3-hydroxybutyrate, but not in the presence of acetoacetate. (-)-Hydroxycitrate also differentially inhibited the incorporation of [2-14C]-leucine and [U-14C]leucine into cerebral lipids. The data show that, although the acetyl moiety of acetyl-CoA generated in brain mitochondria is largely translocated as citrate from these organelles to the cytosol, a cytosolic pathway exists by which acetoacetate is converted directly into acetyl-COA in this cellular compartment.

Acetates↗

Effect of hyperphenylalaninaemia on lipid synthesis from ketone bodies by rat brain.

The effect of hyperphenylalaninaemia on the metabolism of ketone bodies in vivo and in vitro by developing rat brain was investigated. The incorporation in vivo of [14C]acetoacetate into cerebral lipids was decreased by both chronic (for 3 days) and acute (for 6h) hyperphenylalaninaemia induced by injecting phenylalanine into 1-week-old rats. In studies in vitro it was observed that the incorporation of the radioactivity from [14C]acetoacetate and 3-hydroxy[14C]butyrate into cerebral lipids was inhibited by phenyl-pyruvate, but not by phenylalanine. Phenylpyruvate also inhibited the incorporation of 3H from 3H2O into lipids by brain slices metabolizing either 3-hydroxybutyrate or acetoacetate in the presence of glucose. These findings suggest that the decrease in the incorporation in vivo of [14C]acetoacetate into cerebral lipids in hyperphenylalaninaemic rats is most likely caused by phenylpyruvate and not by phenylalanine. Phenylpyruvate as well as phenylalanine had no inhibitory effects on ketone-body-catabolizing enzymes, namely 3-hydroxybutyrate dehydrogenase, 3-oxo acid CoA-transferase and acetoacetyl-CoA thiolase, in rat brain. Phenylpyruvate but not phenylalanine inhibited the activity of the 2-oxoglutarate dehydrogenase complex from rat and human brain. These findings suggest that the metabolism of ketone bodies is impaired in brains of untreated phenylketonuric patients, and in turn may contribute to the diminution of mental development and function associated with phenylketonuria.

Acetoacetates↗

Fatty acid synthesis by human adipose tissue.

The effect of age and nutritional status on the synthesis of fatty acids from a variety of labeled substrates by human adipose tissue in vitro was investigated. The results of this study clearly demonstrate that, although human adipose tissue is able to oxidize glucose to CO2, its ability to incorporate glucose-carbon into long chain fatty acids is negligible. Although the utilization of acetate for the synthesis of fatty acids by adipose tissue is substantial in the presence of glucose and insulin, its physiologic significance in human under normal dietary conditions is questionable. That the capacity of human adipose tissue is limited is further supported by (1) a negligible incorporation of pyruvate-3-14C (up to 25 mM concentration in the incubation medium) into fatty acids, (2) a lack of stimulation in lipogenesis by human adipose tissue after refeeding a diet high in carbohydrate and very low in fat to a previously starved human, and (3) an extremely low activity of pyruvate carboxylase and ATP-citrate lyase in adipose tissues from humans of varying ages. The activities of other key lipogenic enzymes, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-malate dehydrogenase, are also low. These enzymes can be stimulated in human adipose tissue after a fasting-refeeding regimen. The activity of phosphoenolpyruvate carboxykinase is also very low in human adipose tissue,and it is suggested that a pathway of glyceroneogenesis may not play a significant role in human adipose tissue. In light of our results, together with previous reports, it is possible to conclude that the capacity of human adipose tissue to utilize a dietary carbohydrate for the synthesis of fatty acids is extremely low and that the liver plays a major role in the biosynthesis of endogenous fatty acids from dietary carbohydrate in the human.

Acetates↗

Inhibition by the branched-chain 2-oxo acids of the 2-oxoglutarate dehydrogenase complex in developing rat and human brain.

1. The effect of the branched-chain amino acids, namely leucine, isoleucine and valine and their corresponding 2-oxo acids on the metabolism of 2-oxoglutarate by developing rat and human brain preparations was investigated. 2. The decarboxylation of 2-oxo[1-(14)C]glutarate to (14)CO(2) by mitochondria from adult rat brain was inhibited by the branched-chain 2-oxo acids whereas the branched-chain amino acids had no inhibitory effect on this process. 3. The activity of 2-oxoglutarate dehydrogenase complex was about 0.2unit/g of brain from 2-day-old rats and increased by about fourfold reaching an adult value by the end of the third postnatal week. 4. The K(m) value for 2-oxoglutarate of the 2-oxoglutarate dehydrogenase complex in rat and human brain was 100 and 83mum respectively. 5. The branched-chain 2-oxo acids competitively inhibited this enzyme from suckling and adult rats brains as well as from foetal and adult human brains, whereas the branched-chain amino acids had no effect on this enzyme. 6. Approximate K(i) values for the branched-chain 2-oxo acids found for this enzyme were in the range found for these 2-oxo acids in plasma from patients with maple-syrup-urine disease. 7. The possible significance of the inhibition by the branched-chain 2-oxo acids of the 2-oxoglutarate dehydrogenase complex in brains of untreated patients with maple-syrup-urine disease is discussed in relation to the energy metabolism and the biosynthesis of lipids from ketone bodies.

Age Factors↗