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

The hepatic branched-chain alpha-keto acid dehydrogenase complex plays an important role in regulating branched-chain amino acid levels. These compounds are essential for protein synthesis but are toxic if present in excess. When dietary protein is deficient, the hepatic enzyme is present in the inactive, phosphorylated state to allow conservation of branched-chain amino acids for protein synthesis. When dietary protein is excessive, the enzyme is in the active, dephosphorylated state to commit the excess branched-chain amino acids to degradation. Inhibition of protein synthesis by cycloheximide, even when the animal is starving for protein, results in activation of the hepatic branched-chain alpha-keto acid dehydrogenase complex to prevent accumulation of branched-chain amino acids. Likewise, the increase in branched-chain amino acids caused by body wasting during starvation and uncontrolled diabetes is blunted by activation of the hepatic branched-chain alpha-keto acid dehydrogenase complex. The activity state of the hepatic branched-chain alpha-keto acid dehydrogenase complex is regulated in the short term by the concentration of branched-chain alpha-keto acids (inhibitors of branched-chain alpha-keto acid dehydrogenase kinase) and in the long term by alteration in the total branched chain alpha-keto acid dehydrogenase kinase activity.
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PMID:Nutritional and hormonal regulation of the activity state of hepatic branched-chain alpha-keto acid dehydrogenase complex. 263 49

The activation state of branched-chain alpha-keto acid dehydrogenase (BCDH) was studied in rat hindlimb muscles during starvation and insulinopenic diabetes, conditions in which circulating branched-chain amino acids (BCAA) are increased and their oxidation is accelerated. Muscle BCDH is predominantly inactive (phosphorylated) in postabsorptive rats but is activated by increased circulating leucine. Diabetes (streptozotocin-induced and spontaneous BB/W) increased circulating BCAA four- to fivefold and BCDH activity approximately threefold. Insulin treatment caused near normalization of circulating BCAA without correcting BCDH activity. Adrenalectomy of diabetics decreased (without normalizing) circulating BCAA and BCDH activation. Starvation caused mild, progressive increases in circulating BCAA and significant activation of BCDH only after 4 days. Leucine infusion activated BCDH in muscle but the activation by leucine was markedly blunted by diabetes. In isolated perfused hindlimbs (control and diabetic) insulin did not affect BCDH significantly; perfusion with leucine activated BCDH, and this response appeared blunted in diabetics. Activation of muscle BCDH may contribute to increased BCAA catabolism in diabetes; the blunted activation response to hyperleucinemia may spare BCAA and contribute to their persistent elevation in plasma.
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PMID:Effects of diabetes and starvation on skeletal muscle branched-chain alpha-keto acid dehydrogenase activity. 296 88

The effects of acute exercise and starvation on hepatic branched-chain alpha-keto acid dehydrogenase (BCKDH) complex activity were examined in female rats fed high (30%)- or low (8%)-protein diets. The total activity of the complex was significantly higher in the high protein-fed rats than in the low protein-fed rats but was not affected by acute exercise and starvation in either diet group. The proportion of the active form of BCKDH complex was less than 10% in both diet groups. Acute exercise and starvation markedly increased the active form of the complex in both diet groups. The activity of BCKDH kinase, which is responsible for inactivation of the BCKDH complex by phosphorylation, tended to be decreased by acute exercise and starvation in both diet groups. These results suggest that the activity of the BCKDH kinase is an important factor determining the proportion of the active form of BCKDH complex in exercise and starvation, and that the female rat is a useful model for studying the regulation of hepatic BCKDH complex activity.
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PMID:Hepatic branched-chain alpha-keto acid dehydrogenase complex in female rats: activation by exercise and starvation. 1052 49

Branched-chain amino acids are toxic in excess but have to be conserved for protein synthesis. This is accomplished in large part by control of the activity of the branched-chain alpha-keto acid dehydrogenase complex by phosphorylation/dephosphorylation. Regulation of the activity of the hepatic enzyme appears particularly important, at least in rats, since an exceptional high activity of the complex in this tissue makes the liver the primary clearing house for excess branched-chain alpha-keto acids released by other tissues. The degree to which the branched-chain alpha-keto acid dehydrogenase complex is inactivated by phosphorylation is determined by the activity of the branched-chain alpha-keto acid dehydrogenase kinase, which is itself regulated by allosteric effectors as well as factors that affect its level of expression. Well established among these are the alpha-keto acid produced by leucine transamination, which is a potent inhibitor of the kinase, and starvation for dietary protein, which causes increased expression of the branched-chain alpha-keto acid dehydrogenase kinase. The latter finding resulted in the working hypothesis that nutrients and hormones regulate expression of the branched-chain alpha-keto acid dehydrogenase kinase. Evidence has been obtained for the involvement of thyroid hormone, glucocorticoids and ligands for peroxisome proliferator-activated receptor alpha. Thyroid hormone induces, whereas glucocorticoids and peroxisome proliferator-activated receptor alpha ligands repress, expression of the kinase. Increased blood levels of thyroid hormone are proposed to be responsible for increased expression of branched-chain alpha-keto acid dehydrogenase kinase in animals starved for protein.
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PMID:Regulation of branched-chain alpha-keto acid dehydrogenase kinase expression in rat liver. 1123 71

The aim of the present study was to investigate changes in the activity of branched-chain alpha-keto acid dehydrogenase (BCKAD) in skeletal muscle and the heart during brief and prolonged starvation. Fed control rats and rats starved for 2, 4 and 6 days were anesthetized with pentobarbital sodium before heart and hindlimb muscles were frozen in situ by liquid nitrogen. Basal (an estimate of in vivo activity) and total (an estimate of enzyme amount) BCKAD activities were determined by measuring the release of 14CO2 from alpha-keto[1-(14)C]isocaproate. The activity state of BCKAD complex was calculated as basal activity in percentages of total activity. Both basal and total activities and the activity state of the BCKAD were lower in skeletal muscles than in the heart. In both tissues, starvation for 2 or 4 days caused a decrease in the basal activity and activity state of BCKAD. On the contrary, in the heart and muscles of animals starved for 6 days a marked increase in basal activity and activity state of BCKAD was observed. The total BCKAD activity was increasing gradually during starvation both in muscles and the heart. The increase was significant in muscles on the 4th and 6th day of starvation. The demonstrated changes in BCKAD activity indicate significant alterations in branched-chain amino acid (BCAA) and protein metabolism during starvation. The decreased BCKAD activity in skeletal muscle and heart observed on the 2nd and 4th day of starvation prevents the loss of essential BCAA and is an important factor involved in protein sparing. The increased activity of BCKAD on the 6th day of starvation indicates activated oxidation of BCAA and accelerated protein breakdown.
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PMID:Effect of starvation on branched-chain alpha-keto acid dehydrogenase activity in rat heart and skeletal muscle. 1130 Feb 23

Branched-chain alpha-keto acid dehydrogenase kinase is responsible for the inactivation and phosphorylation of the branched-chain alpha-keto acid dehydrogenase complex, the enzyme that catalyses the committed step of branched-chain amino acid catabolism. The activity of the branched-chain alpha-keto acid dehydrogenase complex is inversely correlated with kinase activity, suggesting that the relative activity of the kinase is the primary regulator of the activity of the complex. It has been shown that kinase activity and expression are affected by nutritional states imposed by low-protein diet feeding, starvation, diabetes, and exercise. Evidence has also been presented that certain hormones, particularly insulin, glucocorticoid, thyroid hormone and female sex hormones, affect the activity and expression of the kinase. The findings indicate that nutritional and hormonal control of the activity and expression of branched-chain alpha-keto acid dehydrogenase kinase provides an important means of control of the activity of the branched-chain alpha-keto acid dehydrogenase complex, with inactivation serving to conserve branched-chain amino acids for protein synthesis in some situations and activation serving to provide carbon for gluconeogenesis in others.
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PMID:Regulation of branched-chain amino acid catabolism: nutritional and hormonal regulation of activity and expression of the branched-chain alpha-keto acid dehydrogenase kinase. 1156 2

Sugar starvation exerted by sub-10 mM levels of sucrose on Arabidopsis T87 suspension-cultured cells triggered marked accumulation of the transcripts of genes for E1beta and E2 subunit of the branched-chain alpha-keto acid dehydrogenase complex. Similar levels of sugar starvation increased the luciferase activity in transgenic tobacco BY-2 lines expressing the Arabidopsis E1beta- or E2-promoter-luciferase fusion gene. These results indicate that sugar levels tightly regulate the E1beta and E2 promoter activity in the heterologous plant system. We further showed in the transgenic tobacco BY-2 lines that sugar-starvation-induced activation of the E1beta and E2 promoters was prevented by K-252a, an inhibitor of Ser/Thr protein kinase, and was enhanced by okadaic acid, an inhibitor of protein phosphatases. By contrast, the cauliflower mosaic virus 35S promoter activity in sugar-starved BY-2 cells was not significantly affected by K-252a and only slightly enhanced by okadaic acid. Taken together, we propose that transcriptional activation of genes for the branched-chain alpha-keto acid dehydrogenase complex and its modulation by specific protein kinases/phosphatases are of critical importance in branched-chain amino acid catabolism in plant cells under sugar starvation.
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PMID:Activation of the promoters of Arabidopsis genes for the branched-chain alpha-keto acid dehydrogenase complex in transgenic tobacco BY-2 cells under sugar starvation. 1191 81