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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data are presented on the metabolic and endocrine effects of intravenous infusions in normal fasting man observed under highly controlled conditions over a period of six to eight days duration. There are comparative data on a variety of intravenous feeding programs. The data on total starvation are based on studies from the literature, some of which were carried out in this laboratory. The data on low dose glucose, high dose glucose, glycerol, fat emulsion, and amino acids, each given separately, demonstrate changes seen with simple infusion of a single substrate in fasting. These data are now compared with the utilization of amino acid infusions when accompanied by low dose glucose, high dose glucose, glycerol, and fat emulsion. In all, nine experimental intravenous feeding programs are presented, based on data from 35 subjects observed over a total of 370 subject-days. The findings show a strong interaction between glucose or lipid and protein metabolism. In fasting, glucose had protein sparing effect, most evident when given at high dose. Glycerol, in an amount equal to that contained in 2000 ml of ten per cent fat emulsion, had a mild protein sparing effect. Fat emulsion was no more effective. When amino acids were given alone, normal fasting human subjects were always in negative nitrogen balance with the daily nitrogen loss half that seen in starvation alone. Although amino acids given alone have a protein sparing effect, this is accomplished only at the expense of a high nitrogen excretion including an amount equivalent to the entire infusion plus an additional loss from the body's native proteins. The provision of energy yielding non-protein substrates with the amino acids markedly improved nitrogen economy in the following order: glycerol, low dose glucose, fat emulsion and high dose glucose. When caloric provision with glucose approached the isocaloric level for normal diet, the utilization of amino acids was maximized. When given with amino acids, fat emulsion was more effective than the available glycerol alone. THE ACCOMPANYING ENDOCRINE AND BIOCHEMICAL CHANGES SUGGEST THAT THE MILIEU FOR IDEAL UTILIZATION OF INFUSED AMINO ACIDS IS VARIABLE: ketones at low range (carbohydrate) or moderately elevated (fat emulsion); insulin elevated (carbohydrate) or unchanged (fat emulsion). The utilization of the infused amino acids was markedly improved in both endocrine settings, suggesting that it is the provision of energy as substrate as well as the endocrine setting that determines amino acid utilization. There were other changes in plasma intermediates, particularly fatty acids, glucose and urea, all consistent with the concept that when amino acids are given without other substrates, the amino acids must be maximally utilized for gluconeogenesis. When other substrates are provided (particularly glucose at high dose) then this mandate no longer exists and protein synthesis from the amino acids is favored. Several of the plasma amino acid concentrations responded to glucose when added to amino acid infusion. Amino acids alone produced increases in concentration of all the amino acids found in the infusion with the exception of alanine, arginine, and threonine. Many of these increases were abated by the addition of glucose to the amino acid infusion, suggesting an increased utilization rate. Glycerol and fat emulsion, while modulating increases in the plasma amino acid concentration, did so to a lesser extent than did glucose. This lowering of amino acid concentration was unaccompanied by an increase in urinary excretion. The assumption is therefore made that the provision of the added glucose favors the incorporation of amino acid into protein. There is no evidence from these data to suggest that a rising concentration of ketones in the blood favors amino acid utilization or protein synthesis.
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PMID:Substrate interaction in intravenous feeding: comparative effects of carbohydrate and fat on amino acid utilization in fasting man. 41 Mar 76

Phosphate starvation induced teichuronic acid synthesis in cells of Bacillus subtilis 168trp-which had previously been grown with excess phosphate. This induction was prevented when protein systhesis was inhibited immediately prior to phosphate starvation and under these conditions cells continued to form teichoic acid. The converse was true when phosphate was added to cells previously grown in a phosphate-limited chemostat. The increase in teichoic acid synthesis normally following phosphate addition was prevented by chloramphenicol or amino acid starvation and cells continued to make teichuronic acid. This suggestion that repression of enzyme synthesis is involved in controlling the type of wall polymer made was supported by the low levels of UDP-glucose dehydrogenase found in cells grown with excess phosphate and of CDP-glycerol pyrophosphorylase in phosphate-limited cells. The greater amounts of teichoic acid made under phosphate limitation and of teichuronic acid with excess phosphate when protein synthesis was also inhibited indicated that modulation of enzyme activity occurs. Glycerol starvation of a glycerol-requiring mutant did not derepress teichuronic acid synthesis, indicating that glycerol-containing imtermediates do not act as repressors.
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PMID:Control of teichoic and teichuronic acid biosynthesis in Bacillus subtilis 168trp. Evidence for repression of enzyme synthesis and inhibition of enzyme activity. 81 32

Extracts of Acetobacter xylinum catalyze the phosphorylation of glycerol and dihydroxyacetone (DHA) by adenosine 5'-triphosphate (ATP) to form, respectively, L-alpha-glycerophosphate and DHA phosphate. The ability to promote phosphorylation of glycerol and DHA was higher in glycerol-grown cells than in glucose- or succinate-grown cells. The activity of glycerol kinase in extracts is compatible with the overall rate of glycerol oxidation in vivo. The glycerol-DHA kinase has been purified 210-fold from extracts, and its molecular weight was determined to be 50,000 by gel filtration. The glycerol kinase to DHA kinase activity ratio remained essentially constant at 1.6 at all stages of purification. The optimal pH for both reactions was 8.4 to 9.2. Reaction rates with the purified enzyme were hyperbolic functions of glycerol, DHA, and ATP. The Km for glycerol is 0.5 mM and that for DHA is 5 mM; both are independent of the ATP concentration. The Km for ATP in both kinase reactions is 0.5 mM and is independent of glycerol and DHA concentrations. Glycerol and DHA are competitive substrates with Ki values equal to their respective Km values as substrates. D-Glyceraldehyde and l-Glyceraldehyde were not phosphorylated and did not inhibit the enzyme. Among the nucleotide triphosphates tested, only ATP was active as the phosphoryl group donor. Fructose diphosphate (FDP) inhibited both kinase activities competitively with respect to ATP (Ki= 0.02 mM) and noncompetitively with respect to glycerol and DHA. Adenosine 5'-diphosphate (ADP) and adenosine 5'-monophosphate (AMP) inhibited both enzymic activities competitively with respect to ATP (Ki (ADP) = 0.4 mM; Ki (AMP) =0.25 mM). A. xylinum cells with a high FDP content did not grow on glycerol. Depletion of cellular FDP by starvation enabled rapid growth on glycerol. It is concluded that a single enzyme from A. xylinum is responsible for the phosphorylation of both glycerol and DHA. This as well as the sensitivity of the enzyme to inhibition by FDP and AMP suggest that it has a regulatory role in glycerol metabolism.
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PMID:Phosphorylation of glycerol and dihydroxyacetone in Acetobacter xylinum and its possible regulatory role. 95 17

Glycerol starvation of an Escherichia coli glycerol auxotroph results in a specific inhibition of membrane phospholipid synthesis. Mindich ((1972) J. Bacteriol. 110, 96-102) observed only a trace accumulation of free fatty acid following glycerol deprivation. We have repeated these experiments using glycerol auxotrophs which also possess a lesion in beta oxidation. This defect was introduced in order to control fatty acid degradation. In contrast to the previous results, we find free fatty acid does accumulate during glycerol starvation. Similar results were found using beta oxidation-defective (fadE-) derivatives of both gpsA and plsB glycerol auxotrophs. Upon glycerol starvation of a plsB- fadE- strain, phospholipid synthesis is 90 percent inhibited. Following a lag of 20 to 40 min, free fatty acid synthesis begins and proceeds at a rate that steadily increases until the rate of fatty acid synthesis is equal to that found in glycerol-supplemented cultures. The accumulation of free fatty acid is the result of de novo synthesis. The average chain length of the fatty acid in the unesterified fraction is abnormally long. Two 20-carbon fatty acids, cis-13-eicosenoic acid and arachidic acid, are found in this frction. Furthermore, a greatly increased level of stearic acid and a small amount of a C-22 (behenic) acid are found in the free fatty acid fraction. These data indicate that acyl transfer into phospholipid is a major determinant of phospholipid acyl moiety chain length. Other experiments have shown that the free fatty acid fraction in glycerol-starved cells is metabolically active. This fraction turns over despite the defective beta oxidation system. Restoration of glycerol to starved cells allows the incorporation of the unesterified fatty acids into phospholipid.
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PMID:Regulation of membrane lipid synthesis in Escherichia coli. Accumulation of free fatty acids of abnormal length during inhibition of phospholipid synthesis. 109 44

During the first half of gestation in the rat, maternal net body weight increases rapidly, whereas in the second half of gestation, the mass of maternal structures declines, coincident with the rate of maternal fat accumulation. Enhanced maternal food intake, extrahepatic tissue lipoprotein lipase (LPL) activity, and adipose tissue lipogenesis are responsible for the progressive accumulation of maternal fat. However, during late gestation, decreased fat synthesis in maternal adipose tissue, enhanced lipolytic activity, and decreased LPL activity deplete maternal fat depots. These changes, plus enhanced endogenous production of triglyceride-rich lipoproteins, are also responsible for maternal hypertriglyceridemia. This condition benefits the offspring in two ways: 1) enhanced LPL activity in maternal liver when fasting increases triglyceride consumption for ketone body synthesis, giving the basis for accelerated starvation; and 2) induction of LPL activity in the mammary gland before parturition diverts maternal circulating triglycerides to milk synthesis in preparation for lactation. The magnitude of the maternal-fetal glucose transfer was higher than that of any of the other substrates studied, including alanine, and despite actions to spare glucose, this transfer causes maternal hypoglycemia, which is especially intense in the fasting condition. This increases sympathoadrenal activity in the mother, which may contribute to her active gluconeogenesis. Glycerol was a more efficient glucose precursor than alanine and pyruvate, and whereas glycerol placental transfer is very small, it is proposed that the fetus benefits from this product of adipose tissue lipolysis when it is previously converted into glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intermediary metabolism in pregnancy. First theme of the Freinkel era. 174 73

The basal blood glycerol concentration was determined and the rate of glycerol turnover was assessed by a nonradioactive infusion technique in six healthy nonobese adults after an overnight fast and again after four days of total starvation. Simultaneously, estimates of total energy expenditure and net fat oxidation were made from measurements of oxygen consumption, carbon dioxide production, and urinary nitrogen excretion. The data were combined to provide quantitative estimates of the activity of the triglyceride/fatty acid cycle. The basal concentration of glycerol in venous blood rose from a mean value of 54 +/- 8 mumol/L (SEM) before starvation to 154 +/- 5 mumol/L on day 4 of starvation. Glycerol turnover rates correlated well with the basal blood glycerol concentration (r = .95) and increased from a mean value of 115 +/- 17 mumol/min before starvation (equivalent to mobilization of about 3.95 kJ triglyceride/min) to 304 +/- 20 mumol/min (equivalent to mobilization of about 18.41 kJ/min). The estimated rate of net fat oxidation was 3.00 +/- 0.47 kJ/min before starvation and 4.00 +/- 0.14 kJ/min on day +4 of starvation. The rate of triglyceride energy recycling or rate of deposition of triglyceride energy into fat stores was calculated from the difference in the rate of fat energy mobilization and the rate of energy released during net fat oxidation. The values were found to be 0.94 +/- 0.26 kJ/min before starvation and 6.29 +/- 0.54 kJ/min on day +4 of starvation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The energy cost of triglyceride-fatty acid recycling in nonobese subjects after an overnight fast and four days of starvation. 382 5

While malnutrition attending cancer cachexia may be associated with variable losses of body fat, lipid metabolism has been only minimally studied. To clarify potential aberrations of lipid metabolism in weight losing cancer patients, the whole body rate of lipolysis was determined in 9 cancer patients in the postabsorptive state and compared to that in 5 normal subjects. A primed-three stage infusion of glycerol was used to measure plasma glycerol clearance and turnover. A positive correlation between glycerol turnover and plasma concentration was demonstrated in both cancer patients (r = 0.72) and in normal subjects (r = 0.81). Glycerol turnover rate in cancer patients (2.05 +/- 0.14 mumol X kg-1 X min-1) was not different from that in normals (2.31 +/- 0.50); while glycerol clearance in cancer patients (1.72 +/- 0.13 L/min) was significantly lower (P less than 0.025) by 32% than that in normals. This study demonstrates that the whole body lipolytic rate in cancer patients is not different from healthy normals. As a consequence, the loss of body fat in patients with cancer cachexia may be due to a reduced rate of lipogenesis rather than augmented lipolysis as is observed in nonmalignant malnutrition, starvation, or injury.
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PMID:Cancer cachexia and the rate of whole body lipolysis in man. 395 2

In order to relate the biogenesis of the lactose transport system to lipid synthesis, a glycerol-requiring mutant of Escherichia coli K-12 with a specific defect in l-glycerol-3-phosphate synthesis was isolated and characterized. The defective enzyme is the biosynthetic l-glycerol-3-phosphate dehydrogenase [l-glycerol-3-phosphate: NAD (P) oxidoreductase, EC 1.1.1.8] which functions as a dihydroxyacetone phosphate reductase to provide l-glycerol-3-phosphate for lipid synthesis. In this mutant, removal of glycerol from the growth medium results in inhibition of the synthesis of protein, deoxyribonucleic acid, and phospholipid. Inhibition of phospholipid synthesis immediately follows glycerol removal, whereas the inhibition of deoxyribonucleic acid and protein synthesis is preceded by a short lag period. Glycerol starvation does not change the turnover pattern of previously synthesized phospholipids. The blocking of lipid synthesis by glycerol starvation causes a drastic decrease in inducibility of beta-galactoside transport activity relative to beta-galactosidase, indicating that induction of lactose transport requires de novo lipid synthesis.
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PMID:Induction of the lactose transport system in a lipid-synthesis-defective mutant of Escherichia coli. 491 67

The oxidation and turnover of plasma glycerol has been studied in lean and obese, fed and starving man by means of a long-term infusion of glycerol-(14)C, and the participation of glycerol in gluconeogenesis has been determined. Under none of the experimental conditions did glycerol contribute more than 10% of the total respiratory CO(2). Glycerol turnover in fed lean subjects was 106 mmoles/min. Glycerol levels and turnover were higher in the obese subjects and with all subjects after starvation. There was a direct correlation between plasma levels and turnover values for which a regression equation was derived: y = 1556 x + 33.1, when y = turnover in micromoles per minute and x = glycerol level in micromoles per milliliter. Whereas a direct relation was established between glycerol and FFA levels, the FFA/glycerol turnover ratio was 4.7:1 in the lean group indicating incomplete hydrolysis of adipose tissue triglycerides.During starvation plasma glycerol is nearly or completely converted to glucose in the lean and obese groups, respectively. Of the new glucose formed from protein and glycerol 38% is derived from glycerol in the lean and 79% in the obese. Protein and glycerol have been shown to be adequate as precursors to supply at least as much glucose as is being oxidized per day.
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PMID:Glycerol turnover and oxidation in man. 502 45

1. Anaerobic formation of lactate from glucose by isolated perfused rat kidney (411mumol/h per g dry wt.) was three times as fast as in aerobic conditions (138mumol/h per g). 2. In aerobic or in anaerobic conditions, the ratio of lactate production to glucose utilization was about 2. 3. Starvation or acidosis caused a decline of about 30% in the rate of aerobic glycolysis. 4. The rate of formation of glucose from lactate by perfused kidney from a well-fed rat, in the presence of 5mm-acetoacetate (83mumol/h per g dry wt.), was of the same order as the rate of aerobic glycolysis. 5. During perfusion with physiological concentrations of glucose (5mm) and lactate (2mm) there were negligible changes in the concentration of either substrate. 6. Comparison of kidneys perfused with lactate, from well-fed or starved rats, showed no major differences in contents of intermediates of gluconeogenesis. 7. The tissue concentrations of hexose monophosphates and C(3) phosphorylated glycolytic intermediates (except triose phosphate) were decreased in anaerobic conditions. 8. Aerobic metabolism of fructose by perfused kidney was rapid: the rate of glucose formation was 726mumol/h per g dry wt. and of lactate formation 168mumol/h per g (dry wt.). Glycerol and d-glyceraldehyde were also released into the medium. 9. Aerobically, fructose generated high concentrations of glycolytic intermediates. 10. Anaerobic production of lactate from fructose (74mumol/h per g dry wt.) was slower than the aerobic rate. 11. In both anaerobic and aerobic conditions the ratio [lactate]/[pyruvate] in kidney or medium was lower during perfusion with fructose than with glucose. 12. These results are discussed in terms of the regulation of renal carbohydrate metabolism.
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PMID:Carbohydrate metabolism in the isolated perfused rat kidney. 508 98


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