Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Tacrolimus is widely used for immunosuppressant therapy, including various organ transplantations. One of its main side effects is hyperglycemia due to reduced insulin secretion, but the mechanism remains unknown. We have investigated the metabolic effects of tacrolimus on insulin secretion at a concentration that does not influence insulin content. Twenty-four-hour exposure to 3 nM tacrolimus reduced high glucose (16.7 mM)-induced insulin secretion (control 2.14 +/- 0.08 vs. tacrolimus 1.75 +/- 0.02 ng.islet(-1).30 min(-1), P < 0.01) without affecting insulin content. In dynamic experiments, insulin secretion and NAD(P)H fluorescence during a 20-min period after 10 min of high-glucose exposure were reduced in tacrolimus-treated islets. ATP content and glucose utilization of tacrolimus-treated islets in the presence of 16.7 mM glucose were less than in control (ATP content: control 9.69 +/- 0.99 vs. tacrolimus 6.52 +/- 0.40 pmol/islet, P < 0.01; glucose utilization: control 103.8 +/- 6.9 vs. tacrolimus 74.4 +/- 5.1 pmol.islet(-1).90 min(-1), P < 0.01). However, insulin release from tacrolimus-treated islets was similar to that from control islets in the presence of 16.7 mM alpha-ketoisocaproate, a mitochondrial fuel. Glucokinase activity, which determines glycolytic velocity, was reduced by tacrolimus treatment (control 65.3 +/- 3.4 vs. tacrolimus 49.9 +/- 2.8 pmol.islet(-1).60 min(-1), P < 0.01), whereas hexokinase activity was not affected. These results indicate that glucose-stimulated insulin release is decreased by chronic exposure to tacrolimus due to reduced ATP production and glycolysis derived from reduced glucokinase activity.
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PMID:Tacrolimus suppresses glucose-induced insulin release from pancreatic islets by reducing glucokinase activity. 1547 52