Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leucine aminotransferase (EC 2.6.1.6) and 2-oxoisocaproate dehydrogenase (EC 1.2.4.3) were studied in rat cerebral cortex, cerebellum, brain stem, liver, and muscle in normal and animals starved for 48 hours. In the brain, leucine aminotransferase, valine aminotransferase, and 2-oxoisocaproate dehydrogenase showed a significant increase in starvation only in cerebellum while there was increase in 2-oxoisocaproate dehydrogenase in cerebral cortex only. A significantly high increase in the activity of 2-oxoisocaproate dehydrogenase was observed in muscle in starvation. A significant decrease in the activity of leucine aminotransferase was observed in liver in starvation. The increase in the activity of 2-oxoisocaproate dehydrogenase in muscle and a decrease in the activity of leucine aminotransferase in liver in starvation indicate that the leucine is predominantly metabolized in extra hepatic tissues particularly in muscle. As a result of intraperitoneal administration of 2 ml of leucine (5 mM), a significant increase in 2-oxoisocaproate dehydrogenase occurred in cerebral cortex, liver, and muscle while a profound increase in the activity of glutamate dehydrogenase (EC 1.4.1.2) was observed in all the brain regions and liver under these conditions. A significant increase in the content of glutamic acid, alanine, and GABA was observed in all the three regions of the brain after the administration of leucine. A significant increase in the content of glutamine was observed only in the cerebellum and cerebral cortex after leucine administration. These results indicate that leucine in brain might contribute to the formation of glutamate, not only by transamination, but also by promoting glutamate dehydrogenase activity. Thus, there is a change in the metabolism of glutamate family of amino acids and energy depletion. These results are discussed in relation to the brain function.
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PMID:Studies on metabolism of branched chain amino acids in brain and other tissues of rat with special reference to leucine. 714 88

Four mitochondrial protein kinases have been cloned. These proteins represent a new family of protein kinases, related by sequence to the bacterial protein kinases but by function to the eukaryotic serine protein kinases. Arg288 is required for recognition by BCKDK of the phosphorylation site on the E1alpha subunit of the BCKDH complex. BCKDK inhibits the dehydrogenase activity of the BCKDH complex by introducing a negative charge into the active-site pocket of the E1 component. Protein starvation of rats induces an increase in the amount of BCKDK bound to the BCKDH complex. This causes inactivation of the BCKDH complex and conserves branched-chain amino acids for protein synthesis in the protein-starved state. Expression of the different PDK isoenzymes is tissue specific, and the different PDK isoenzymes are unique with respect to kinetic parameters for ATP and ADP and sensitivity to allosteric effectors (NADH, NAD+, coenzyme A, acetyl-CoA, pyruvate, and dichloroacetate). Preliminary experiments indicate that an increased amount of PDK2 protein partly explains the increase in PDK activity that occurs in rat liver in response to chemically induced diabetes.
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PMID:Mitochondrial alpha-ketoacid dehydrogenase kinases: a new family of protein kinases. 934 45

Branched-chain alpha-keto acid dehydrogenase (BCKDH), a multienzyme complex, plays a key role in branched-chain amino acid catabolism. However, it remains unclear whether expression of each subunit is coordinately regulated in plants, which should be important for the efficient assembly of subunits into a functional multienzyme complex. We show that the transcripts from the Arabidopsis E1alpha subunit gene accumulated in dark-adapted leaves and in sugar-starved suspension cells. These results are complementary to our previous report that the transcripts for the E1beta and E2 subunit genes accumulated in sugar-starved cells. Expression of the E1alpha gene is likely to be regulated by hexokinase-mediated sugar signaling, indicating that sugar plays a regulatory role in the coordinated expression of BCKDH subunit genes. Furthermore, Leu and its metabolite alpha-ketoisocaproate have synergistic effects on the enhanced expression of BCKDH subunit genes under sugar starvation. We hence suggest that branched-chain amino acids activate their own degradation pathway in sugar-starved cells through co-induction of each subunit gene of BCKDH.
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PMID:Leucine and its keto acid enhance the coordinated expression of genes for branched-chain amino acid catabolism in Arabidopsis under sugar starvation. 1141 32

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