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

Knowledge of the structure of actin in its various conformational states is important for understanding the diverse motile activities carried out by eukaryotic cells. Profilin:actin crystals provide a unique system for studying conformational states of actin, because they exhibit a high degree of polymorphism in response to environmental conditions while maintaining crystalline order. A preliminary comparison of two states of profilin:beta-actin crystals shows that crystal polymorphism involves movements of actin subdomains at hinge points homologous to those found in hexokinase, a protein whose polypeptide fold is related to actin. The homology of the hinge points in actin to those in hexokinase suggests that actin subdomain movements in profilin:beta-actin crystals have functional significance. We discuss how these movements could be related to structural transitions between states of filamentous actin in muscle contraction.
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PMID:Structural studies on the ribbon-to-helix transition in profilin: actin crystals. 778 53

A single bout of acute exercise increases hexokinase (HK) II mRNA and enzyme activity [R. M. O'Doherty, D. P. Bracy, H. Osawa, D. H. Wasserman, and D. K. Granner. Am. J. Physiol. 266 (Endocrinol. Metab. 29): E171-E178, 1994]. The present study addresses the mechanism of the increase in HK II mRNA. Male rats undertook a single bout of treadmill exercise and were then killed immediately or after a predetermined recovery period. The gastrocnemius/plantaris muscle complex, composed of mixed fiber types, was excised; the nuclei were isolated; and HK I, HK II, beta-actin, and alpha-tubulin gene transcription rates were measured. Genomic DNA and plasmid DNA were used as positive and negative controls, respectively. Immediately after the cessation of 30, 45, or 90 min of exercise, HK II gene transcription rates were 1.3 +/- 0.3-,2.9 +/- 0.3-, and 4.0 +/- 0.6-fold, respectively, above those of sedentary controls. The increases after 45 and 90 min of exercise were statistically significant (P < 0.01). One hour after the cessation of 30 min of exercise, HK II gene transcription was significantly increased (1.40 +/- 0.03-fold; P < 0.05). At all time points, transcription of the HK I, beta-actin, and alpha-tubulin genes was unchanged. We conclude that the exercise-induced increase in HK II gene transcription appears to play a major role in the increase of HK II mRNA and activity.
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PMID:Transcription of the rat skeletal muscle hexokinase II gene is increased by acute exercise. 887 47

The importance of the glucose transporter isoform, GLUT2, in the construction of glucose-sensitive surrogate insulin-secreting cells was evaluated using murine pituitary AtT20 cells. The cells were double transfected with cDNAs for human preproinsulin (hppI-1) driven by the cytomegalovirus promoter, and human GLUT2 driven by the beta-actin promoter. The stably transfected clone, AtTinsGLUT2.36, which strongly expressed both the hppI-1 and GLUT2 genes, constitutively released 7.5 ng/10(6) cells/24 h of immunoreactive insulin-like material, 75% of which was fully processed mature human insulin. Increasing glucose concentrations in the subphysiological range up to 50 microM increased insulin release, but greater glucose concentrations did not further increase insulin release. Suppression of the low-K(m) glucose-phosphorylating enzyme, hexokinase, with 2-deoxy-D-glucose increased glucose-stimulated insulin release by two- to threefold in the presence of subphysiological and physiological glucose concentrations up to 10 mM. Physiological glucose concentrations increased the amount of GLUT2 mRNA, indicating that the beta-actin promoter responds in a glucose-dependent manner. Implantation of 2 x 10(7) AtTinsGLUT2.36 cells intraperitoneally into streptozotocin-diabetic nude mice slowed the progression of hyperglycaemia. The implanted cells formed vascularised tumour-like cell aggregates attached to the peritoneum. The results demonstrate that the beta-actin promoter is partially regulated by glucose. Expression of GLUT2 enables glucose to enter the cell at high K(m), but high-K(m) glucose phosphorylation is also required to signal glucose-stimulated genes affecting insulin release.
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PMID:Expression of GLUT2 in insulin-secreting AtT20 pituitary cells. 951 84

Nitrosative stress has been implicated in the pathophysiology of several CNS disorders, including multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). We have recently shown that protein nitrosothiols (PrSNOs) accumulate in the brain of MS patients, and there is indirect evidence that PrSNO levels are also increased in EAE. In this study we sought to identify the major PrSNOs in the spinal cord of EAE animals prepared by active immunization of C57/BL6 mice with MOG(35-55) peptide. For this purpose, PrSNOs from control and EAE mice at various disease stages were derivatized with HPDP-biotin, and the biotinylated proteins were isolated with streptavidin-agarose. Proteins from total and streptavidin-bound fractions were then analyzed by Western blotting using antibodies against the major S-nitrosylated substrates of CNS tissue. With this approach we found that the proportion of S-nitrosylated neurofilament proteins, NMDA receptors, alpha/beta-tubulin, beta-actin, and GAPDH is increased in EAE. Other potential substrates either were not S-nitrosylated in vivo (HCN3, HSP-72, CRMP-2, gamma-actin, calbindin) or their S-nitrosylation levels were unaltered in EAE (Na/K ATPase, hexokinase, glycogen phosphorylase). We also discovered that neuronal specific enolase is the major S-nitrosylated protein in acute EAE. Given that S-nitrosylation affects protein function, it is likely that the observed changes are significant to the pathophysiology of inflammatory demyelination.
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PMID:Identification of major S-nitrosylated proteins in murine experimental autoimmune encephalomyelitis. 1940 5