Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.4.1.2 (acetyl-CoA carboxylase)
 2,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic exposure of pancreatic beta-cells to high glucose has pleiotropic action on beta-cell function. In particular, it induces key glycolytic genes, promotes glycogen deposition, and causes beta-cell proliferation and altered insulin secretion characterized by sensitization to low glucose. Postglycolytic events, in particular, anaplerosis and lipid signaling, are thought to be implicated in beta-cell activation by glucose. To understand the biochemical nature of the beta-cell adaptive process to hyperglycemia, we studied the regulation by glucose of lipogenic genes in the beta-cell line INS-1. A 3-day exposure of cells to elevated glucose (5-25 mmol/l) increased the enzymatic activities of fatty acid synthase 3-fold, acetyl-CoA carboxylase 30-fold, and malic enzyme 1.3-fold. Pyruvate carboxylase and citrate lyase expression remained constant. Similar observations were made at the protein and mRNA levels except for malic enzyme mRNA, which did not vary. Metabolic gene expression changes were associated with chronically elevated levels of citrate, malate, malonyl-CoA, and conversion of glucose carbon into lipids, even in cells that were subsequently exposed to low glucose. Similarly, fatty acid oxidation was suppressed and phospholipid and triglyceride synthesis was enhanced independently of the external glucose concentration in cells preexposed to high glucose. The results suggest that a coordinated induction of glycolytic and lipogenic genes in conjunction with glycogen and triglyceride deposition, as well as increased anaplerosis and altered lipid partitioning, contribute to the adaptive process to hyperglycemia and glucose sensitization of the beta-cell.
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PMID:Long-term exposure of beta-INS cells to high glucose concentrations increases anaplerosis, lipogenesis, and lipogenic gene expression. 964 32

Pyruvate carboxylase (PC) is distributed in many eukaryotes as well as in some prokaryotes. PC catalyzes the ATP-dependent carboxylation of pyruvate to form oxalacetate. PC has three functional domains, one of which is a biotin carboxylase (BC) domain. The BC subunit of PC from Aquifex aeolicus (PC-beta) was crystallized in an orthorhombic form with space group P2(1)2(1)2, unit-cell parameters a = 92.4, b = 122.1, c = 59.0 A and one molecule in the asymmetric unit. Diffraction data were collected at 100 K on BL24XU at SPring-8. The crystal structure was determined by the molecular-replacement method and refined against 20.0-2.2 A resolution data, giving an R factor of 0.199 and a free R factor of 0.236. The crystal structure revealed that PC-beta forms a dimeric quaternary structure consisting of two molecules related by crystallographic twofold symmetry. The overall structure of PC-beta is similar to other biotin-dependent carboxylases, such as acetyl-CoA carboxylase (ACC). Although some parts of domain B were disordered in ACC, the corresponding parts of PC-beta were clearly determined in the crystal structure. From comparison between the active-site structure of ACC with ATP bound and a virtual model of PC-beta with ATP bound, it was shown that the backbone torsion angles of Glu203 in PC-beta change and some of water molecules in the active site of PC-beta are excluded upon ATP binding.
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PMID:Structure of the biotin carboxylase subunit of pyruvate carboxylase from Aquifex aeolicus at 2.2 A resolution. 1499 73


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