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

The total activity of pyruvate dehydrogenase (PDH) complex in rat hind-limb muscle mitochondria was 76.4 units/g of mitochondrial protein. The proportion of complex in the active form was 34% (as isolated), 8-14% (incubation with respiratory substrates) and greater than 98% (incubation without respiratory substrates). Complex was also inactivated by ATP in the presence of oligomycin B and carbonyl cyanide m-chlorophenylhydrazone. Ca2+ (which activates PDH phosphatase) and pyruvate or dichloroacetate (which inhibit PDH kinase) each increased the concentration of active PDH complex in a concentration-dependent manner in mitochondria oxidizing 2-oxoglutarate/L-malate. Values giving half-maximal activation were 10 nM-Ca2+, 3 mM-pyruvate and 16 microM-dichloroacetate. Activation by Ca2+ was inhibited by Na+ and Mg2+. Mitochondria incubated with [32P]Pi/2-oxoglutarate/L-malate incorporated 32P into three phosphorylation sites in the alpha-chain of PDH; relative rates of phosphorylation were sites 1 greater than 2 greater than 3, and of dephosphorylation, sites 2 greater than 1 greater than 3. Starvation ( 48h ) or induction of alloxan-diabetes had no effect on the total activity of PDH complex in skeletal-muscle mitochondria, but each decreased the concentration of active complex in mitochondria oxidizing 2-oxoglutarate/L-malate and increased the concentrations of Ca2+, pyruvate or dichloracetate required for half-maximal reactivation. In extracts of mitochondria the activity of PDH kinase was increased 2-3-fold by 48 h starvation or alloxan-diabetes, but the activity of PDH phosphatase was unchanged.
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PMID:Reversible phosphorylation of pyruvate dehydrogenase in rat skeletal-muscle mitochondria. Effects of starvation and diabetes. 633 93

The contribution that starvation makes to the altered glucose metabolism in injured rats was evaluated. Food intake, weight change, nitrogen balance, and muscle tissue concentrations of glycogen, glucose, and the glycolytic intermediates were determined in these animals. This study concluded that the wounded and pair fed control groups presented adequately represent the metabolic states associated with injury and semistarvation in experimental animals, decreased food intake plays a major role in the weight loss and nitrogen balance in this wound model, wounding overrides two of the controlling steps of glycolysis (hexokinase and phosphofructokinase) in skeletal muscle during starvation, the finding of similar pyruvate dehydrogenase activity after wounding and starvation as demonstrated by tissue lactate to pyruvate ratios and lactate and pyruvate concentrations suggest that lactate production in wounded tissue may not be simply a manifestation of an altered redox state secondary to anaerobic conditions.
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PMID:Effect of starvation on the local and systemic metabolic effects of the lambda-carrageenan wound. 671 47

The effect of long-chain acyl-CoA on subcellular adenine nucleotide systems was studied in the intact liver cell. Long-chain acyl-CoA content was varied by varying the nutritional state (fed and starved states) or by addition of oleate. Starvation led to an increase in the mitochondrial and a decrease in the cytosolic ATP/ADP ratio in liver both in vivo and in the isolated perfused organ as compared with the fed state. The changes were reversed on re-feeding glucose in liver in vivo or on infusion of substrates (glucose, glycerol) in the perfused liver, respectively. Similar changes in mitochondrial and cytosolic ATP/ADP ratios occurred on addition of oleate, but, importantly, not with a short-chain fatty acid such as octanoate. It is concluded that long-chain acyl-CoA exerts an inhibitory effect on mitochondrial adenine nucleotide translocation in the intact cell, as was previously postulated in the literature from data obtained with isolated mitochondria. The physiological relevance with respect to pyruvate metabolism, i.e. regulation of pyruvate carboxylase and pyruvate dehydrogenase by the mitochondrial ATP/ADP ratio, is discussed.
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PMID:Effect of long-chain fatty acyl-CoA on mitochondrial and cytosolic ATP/ADP ratios in the intact liver cell. 674 76

The effect of halothane anaesthesia on the activity of the mitochondrial enzyme pyruvate dehydrogenase was studied in starved lactating rats. Extracts of freeze-clamped mammary gland and liver were assayed for pyruvate dehydrogenase activity. The fraction of the enzyme in the phosphorylated inactive form was increased greatly by starvation or by streptozotocin diabetes, and halothane anaesthesia did not disturb this effect. In starved animals not exposed to halothane, injection of insulin led to a rapid increase in the active fraction of the enzyme in mammary gland but not in liver. In animals under halothane anaesthesia this effect of insulin was largely abolished. The combination of starvation and halothane anaesthesia may impair mitochondrial accumulation of calcium which may be involved in the stimulation of pyruvate dehydrogenase by insulin.
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PMID:Halothane anaesthesia can block insulin stimulation of pyruvate dehydrogenase activity in mammary glands of 24-hour starved lactating rats. 700 Jan 4

Glucose or insulin increased lipogenesis (measured in vivo using 3H2O) in brown fat of starved rats. Such increases were associated with activation of pyruvate dehydrogenase and increased use of glucose as a lipogenic precursor (monitored as an increase in the 14C/3H ratio in brown-fat fatty acids in rats injected with both 3H20 and [U-14C]glucose). (-) Hydroxycitrate did not inhibit basal rates of brown-fat lipogenesis in starved rats but suppressed the increases in lipogenesis and glucose utilization observed in response to insulin. (-)Hydroxycitrate did not, however, inhabit the increase in 14C/3H observed after insulin treatment. The results indicate that in brown fat, glucose is utilized for fatty-acid synthesis predominantly via citrate, and that insulin acts to increase lipogenesis at site(s) prior to citrate cleavage. As basal rates of lipogenesis were not inhibited by (-)hydroxycitrate, it is suggested that acetate may be a lipogenic substrate for brown fat in starvation, and experiments are described which support this suggestion.
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PMID:Brown-adipose-tissue lipogenesis in starvation: effects of insulin and (-) hydroxycitrate. 704 28

1. Previous studies showed that the activation of pyruvate dehydrogenase within intact rat heart mitochondria of pyruvate is much diminished in mitochondria from starved or diabetic animals [see Kerbey, Randle, Cooper, Whitehouse, Pask & Denton (1976) Biochem. J. 154, 327-348]. In the present study, diminished responses to added Ca2+ and ADP were also found in these mitochondria. 2. Starvation or diabetes did not affect the mitochondrial respiratory control ratio of the ATP content. Moreover, starvation and diabetes did not alter the response of the intramitochondrial Ca2+-sensitive enzyme, 2-oxoglutarate dehydrogenase, to changes in the extramitochondrial concentration of Ca2+ and 2-oxoglutarate, thus indicating that there were no appreciable changes in the distribution of Ca2+ and H+ across the mitochondrial inner membrane. 3. Pyruvate, Ca2+ and ADP were found to have synergistic effects on pyruvate dehydrogenase activity, particularly in mitochondria from starved and diabetic rats. 4. The results suggest that the effects of diabetes and starvation on pyruvate dehydrogenase are not brought about by changes in the distribution of these effectors across the mitochondrial inner membrane or by changes in the intrinsic sensitivity of the kinase or phosphatase of the pyruvate dehydrogenase system to pyruvate, Ca2+ or ADP; rather it is probably that there is an increase in the maximum activity of kinase relative to that of the phosphatase. 6. The results also lend further support to the hypothesis that adrenaline may bring about the activation of pyruvate dehydrogenase in the rat heart by an increase in the intramitochondrial concentration of Ca2+.
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PMID:Studies on the interactions of Ca2+ and pyruvate in the regulation of rat heart pyruvate dehydrogenase activity. Effects of starvation and diabetes. 709 23

1. Inactive pyruvate dehydrogenase phosphate complexes were partially purified from hearts of fed, starved or alloxan-diabetic rats by using conditions that prevent phosphorylation or dephosphorylation. 2. Unoccupied sites of phosphorylation were assayed by incorporation of 32P from [gamma-32P]ATP into the complexes. Total sites of phosphorylation were assayed by the same method after complete reactivation, and thus dephosphorylation, of complexes by incubation with pyruvate dehydrogenase phosphate phosphatase. Occupancy is assumed from the difference (total sites--unoccupied sites). Percentage incorporation into individual sites was measured by high-voltage electrophoresis after tryptic digestion. 3. Values (means +/- S.E.M., in nmol of phosphate/unit of inactive complex) for total sites, occupied sites and percentage occupancies, with numbers of observations in parentheses were: fed, 2.1 +/- 0.04, 1.15 +/- 0.04, 54.8 +/- 1.6% (39); starved, 2.05 +/- 0.03, 1.85 +/- 0.03, 90.2 +/- 1.4% (28); alloxan-diabetic, 1.99 +/- 0.03, 1.72 +/- 0.03, 86.4 +/- 1.4% (68%). 4. Values (means +/- S.E.M. for percentage occupancy) for individual sites of phosphorylation in pyruvate dehydrogenase phosphate given in the order sites 1, 2 and 3 were : fed, 100 +/- 2.7, 27.8 +/- 1.6, 33.9 +/- .9; starved, 100 +/- 1.4, 76.2 +/- 2.0, 92.4 +/- 1.5; alloxan-diabetic, 100 +/- 1.2, 64.0 +/- 1.7, 94.6 +/- 1.4. 5. It is concluded that starvation or alloxan-diabetes leads to a 2--3-fold increase in the occupancy of phosphorylation sites 2 and 3 in pyruvate dehydrogenase phosphate in rat heart in vivo.
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PMID:Occupancy of sites of phosphorylation in inactive rat heart pyruvate dehydrogenase phosphate in vivo. 730 68

Molecular cloning has provided evidence for a new family of protein kinases in eukaryotic cells. These kinases show no sequence similarity with other eukaryotic protein kinases, but are related by sequence to the histidine protein kinases found in prokaryotes. These protein kinases, responsible for phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase and pyruvate dehydrogenase complexes, are located exclusively in mitochondrial matrix space and have most likely evolved from genes originally present in respiration-dependent bacteria endocytosed by primitive eukaryotic cells. Long-term regulatory mechanisms involved in the control of the activities of these two kinases are of considerable interest. Dietary protein deficiency increases the activity of branched-chain alpha-ketoacid dehydrogenase kinase associated with the branched-chain alpha-ketoacid dehydrogenase complex. The amount of branched-chain alpha-ketoacid dehydrogenase kinase protein associated with the branched-chain alpha-ketoacid dehydrogenase complex and the message level for branched-chain alpha-ketoacid dehydrogenase kinase are both greatly increased in the liver of rats starved for protein, suggesting increased expression of the gene encoding branched-chain alpha-ketoacid dehydrogenase kinase. The increase in branched-chain alpha-ketoacid dehydrogenase kinase activity results in greater phosphorylation and lower activity of the branched-chain alpha-ketoacid dehydrogenase complex. The metabolic consequence is conservation of branched chain amino acids for protein synthesis during periods of dietary protein deficiency. Two isoforms of pyruvate dehydrogenase kinase have been identified and cloned. Pyruvate dehydrogenase kinase 1, the first isoform cloned, corresponds to the 48 kDa subunit of the pyruvate dehydrogenase kinase isolated from rat heart tissue. Pyruvate dehydrogenase kinase 2, the second isoform cloned, corresponds to the 45 kDa subunit of this enzyme. In addition, it also appears to correspond to a possibly free or soluble form of pyruvate dehydrogenase kinase that was originally named kinase activator protein. Assuming that differences in kinetic and/or regulatory properties of these isoforms exist, tissue specific expression of these enzymes and/or control of their association with the complex will probably prove to be important for the long term regulation of the activity of the pyruvate dehydrogenase complex. Starvation and the diabetic state are known to greatly increase activity of the pyruvate dehydrogenase kinase in the liver, heart and muscle of the rat. This contributes in these states to the phosphorylation and inactivation of the pyruvate dehydrogenase complex and conservation of pyruvate and lactate for gluconeogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A new family of protein kinases--the mitochondrial protein kinases. 757 41

This review examines the molecular mechanisms underlying substrate competition between glucose and lipid in starvation and in insulin-resistant states. We demonstrate that lipid-derived substrates are oxidized in preference to glucose by skeletal muscle in vivo during prolonged starvation. An accelerated and exaggerated lipolytic and ketogenic response to starvation in late pregnancy is associated with more rapid suppression of glucose oxidation by the maternal skeletal-muscle mass. These benign adaptations to changes in lipid availability (which occur secondarily to changes in carbohydrate supply and demand) contrast with the well-documented detrimental effects to health of an inappropriately high supply of dietary lipid. We present results that indicate that the prolonged consumption of a diet high in saturated fat is associated with a stable enhancement of pyruvate dehydrogenase (PDH) kinase activity at least in two oxidative tissues--liver and heart. This long-term enhancement of PDH kinase activity is concomitant with the development of whole-body insulin resistance and adds a new dimension to the potential role of dietary composition in the pathogenesis of insulin resistance.
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PMID:The pyruvate dehydrogenase complex: nutrient control and the pathogenesis of insulin resistance. 778 39

The branched-chain alpha-ketoacid dehydrogenase (BCKDH) and pyruvate dehydrogenase (PDH) complexes are regulated by phosphorylation cycles catalyzed by complex-specific protein kinases and phosphoprotein phosphatases. Molecular cloning of these mitochondrial protein kinases has established a new family of protein kinases in eukaryotes that appears related by primary sequence to the histidine protein kinase family of prokaryotes. Changes in the activities of both kinases that are stable, i.e., not caused directly by allosteric effectors, correlate inversely with the changes in the activity states of the complexes that occur in different nutritional states. For example, BCKDH kinase activity is increased and the BCKDH complex activity state is decreased in rats fed diets deficient in protein. The increase in BCKDH kinase activity is due to an increase in the amount of BCKDH kinase protein bound to the BCKDH complex. The message level for BCKDH kinase also increases in the liver of rats starved for protein, suggesting a pretranslational mechanism exists for the long-term regulation of BCKDH kinase. Starvation and high-fat feeding cause a stable increase in PDH kinase activity and a corresponding decrease in activity state of the PDH complex. The mechanism responsible has not been defined.
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PMID:Nutritional regulation of the protein kinases responsible for the phosphorylation of the alpha-ketoacid dehydrogenase complexes. 778 41


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