Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Promastigotes from late log phase and 3-day stationary phase cultures of Leishmania donovani were collected, washed in buffer, and the cell pellet was treated with boiling KOH. A putative carbohydrate storage material was then precipitated and washed in ethanol/LiBr. This material did not liberate glucose when treated with amyloglucosidase, indicating that it was not glycogen. Acid hydrolysis released a hexose which was identified as mannose by several criteria. Considerably more of this mannan-like carbohydrate is present in cells from 3-day stationary phase than from late log phase cultures, consistent with the ability of 3-day stationary phase cells to survive in non-nutrient buffer and maintain oxygen consumption for longer than log phase cells. The amount of this mannan-like compound decreased by over 50% during a 3-h incubation in buffer of cells from 3-day stationary phase cultures. The presence of glucose during the incubation prevented the utilization of this carbohydrate, consistent with the possibility that it serves as an energy reserve.
Mol Biochem Parasitol 1992 Jul
PMID:Utilization of a carbohydrate reserve comprised primarily of mannose by Leishmania donovani. 150 39

At 3-4 degrees C, the transport of 3-O-methyl-D-glucose (30 mM) was severely impaired in islets prepared from adult rats injected with streptozotocin during the neonatal period. However, at 37 degrees C, the first and second phase of glucose-stimulated insulin release were decreased to the same relative extent in perifused islets of diabetic, as compared to control, animals. Moreover, the time-related increase in the oxidative response of the islets to 16.7 mM D-glucose was less pronounced in diabetic than control rats. The activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase in islet homogenates of diabetic rats only represented one-fifth of that found in control rats, whereas the activity of the cytosolic NAD-glycerophosphate dehydrogenase was comparable in both types of rats. This coincided with the fact that a rise in D-glucose concentration from 2.8 to 16.7 mM failed to increase significantly L-[2-3H]glycerol conversion to 3HOH in islets from diabetic rats, in contrast to the situation found in control animals. The activity of 2-ketoglutarate dehydrogenase in islet homogenates when expressed per microgram protein was not different in control and diabetic rats. Likewise, the ratio between D-[6-14C]glucose oxidation and D-[3,4-14C]glucose oxidation and the capacity of either a non-metabolized analog of L-leucine or 3-phenylpyruvate to preferentially stimulated D-[6-14C]glucose oxidation relative to D-[5-3H]glucose utilization were both unaffected in islets from diabetic rats. These findings argue against the existence of a primary defect in the Krebs cycle of diabetic rats. It is proposed that, despite an obvious alteration of the hexose transport system in the islet cells of diabetic rats, the preferential impairment of the B-cell secretory response to D-glucose, as distinct from other secretagogues, in this model of non-insulin-dependent diabetes is mainly attributable to the low activity of FAD-linked glycerophosphate dehydrogenase, resulting in a decreased metabolic flow through the glycerol phosphate shuttle and a reduced rate of aerobic glycolysis.
Mol Cell Endocrinol 1992 Feb
PMID:Study of hexose transport, glycerol phosphate shuttle and Krebs cycle in islets of adult rats injected with streptozotocin during the neonatal period. 153 53

A cDNA cloned from Trypanosoma brucei brucei codes for a putative membrane protein which is homologous to the erythrocyte glucose transporter and several other sugar transporters from Escherichia coli, yeast, algae and Leishmania. This cDNA hybridizes to a 2.3-kb mRNA that accumulates to a much higher degree in the bloodstream mammalian form than in the procyclic insect form of the parasite. The correlation between the expression of this gene and the hexose metabolism of Leishmania enriettii and T. brucei suggest that these 2 related genes probably encode hexose transporters. The gene encoding this mRNA is a member of a multigene family. The putative hexose transporter gene is highly conserved among Kinetoplastidae, indicating an important role for this protein in the parasite life cycle.
Mol Biochem Parasitol 1992 May
PMID:A potential hexose transporter gene expressed predominantly in the bloodstream form of Trypanosoma brucei. 162 98

The exchange of protons and deuterons by phosphoglucoisomerase during the single passage conversion of D-[2-13C,1-2H]fructose 6-phosphate in H2O or D-[2-13C]fructose 6-phosphate in D2O to D-[2-13C]glucose 6-phosphate, as coupled with the further generation of 6-phospho-D-[2-13C]gluconate in the presence of excess glucose-6-phosphate dehydrogenase was investigated by 13C NMR spectroscopy of the latter metabolite. In H2O, the intramolecular deuteron transfer from the C1 of D-fructose 6-phosphate to the C2 of D-glucose 6-phosphate amounted to 65%, a value only slightly lower than the 72% intramolecular proton transfer in D2O. Both percentages, especially the latter one, were lower than those previously recorded during the single passage conversion of D-[1-13C,2-2H]glucose 6-phosphate in H2O or D-[1-13C]glucose 6-phosphate in D2O to D-fructose 6-phosphate and then to D-fructose 1,6-bisphosphate. These differences indicate that the sequence of interactions between the hexose esters and the binding sites of phosphoglucoisomerase is not strictly in mirror image during, respectively, the conversion of the aldose phosphate to ketose phosphate and the opposite process.
Mol Cell Biochem 1991 May 15
PMID:Phosphoglucoisomerase-catalyzed interconversion of hexose phosphates. Study by 13C NMR of proton and deuteron exchange. 164 80

The nucleotide sequence of a 5.1 kb fragment from the streptomycin biosynthetic gene cluster from Streptomyces griseus revealed the presence of five open reading frames which form part of two convergently oriented transcription units strDEL and strNB2M. The coding capacity for polypeptide products was calculated to be 35.7 kDa (StrE), 32.2 kDa (StrL), 35.6 kDa (StrN), 38.2 kDa (StrB2), and 21.9 kDa (StrM), respectively. Various observations suggested that the gene products StrD (dTDP-glucose synthase), StrE (dTDP-glucose dehydratase), StrM (dTDP-4-keto-6-deoxyglucose 3,5-epimerase), and StrL (dTDP-dihydrostreptose synthase) are involved in biosynthesis of the streptose moiety of streptomycin. StrE and StrL are significantly similar in primary structure to each other and to other oxidoreductases (epimerases) involved in hexose metabolism. Genes for dTDP-glucose synthase and dehydratase occur in other gene clusters for antibiotic production. Therefore, the strD and strE genes could serve as universal probes indicative of the presence of biosynthetic capacity for 6-deoxyhexose moieties. The StrB2 protein showed 69% amino acid identity to the first-step amidinotransferase StrB1. The presence of both strB genes appears to be the result of a gene duplication event. The gene product StrN contains sequence motifs also conserved in the putative catalytic and/or substrate recognition domains of aminoglycoside phosphotransferases and eucaryotic protein kinases. The possible role of a TTA codon, located near the start of the strN reading frame, in regulation of the str cluster is discussed.
Mol Gen Genet 1991 Dec
PMID:Genetics of streptomycin production in Streptomyces griseus: molecular structure and putative function of genes strELMB2N. 166 69

We show that D- but not L-hexoses modulate the accumulation of radioactive vinblastine in injected Xenopus laevis oocytes expressing the murine Mdr1b P-glycoprotein. We also show that X. laevis oocytes injected with RNA encoding the rat erythroid/brain glucose transport protein (GLUT1) and expressing the corresponding functional transporter exhibit a lower accumulation of [3H]vinblastine and show a greater capacity to extrude the drug than do control oocytes not expressing the rat GLUT1 protein. Cytochalasin B and phloretin, two inhibitors of the mammalian facilitative glucose transporters, can overcome the reduced drug accumulation conferred by expression of the rat GLUT1 protein in Xenopus oocytes but have no significant effect on the accumulation of drug by Xenopus oocytes expressing the mouse Mdr1b P-glycoprotein. These drugs also increase the accumulation of [3H]vinblastine in multidrug-resistant Chinese hamster ovary cells. Cytochalasin E, an analog of cytochalasin B that does not affect the activity of the facilitative glucose transporter, has no effect on the accumulation of vinblastine by multidrug-resistant Chinese hamster cells or by oocytes expressing either the mouse Mdr1b P-glycoprotein or the GLUT1 protein. In all three cases, the drug verapamil produces a profound effect on the cellular accumulation of vinblastine. Interestingly, although immunological analysis indicated the presence of massive amounts of P-glycoprotein in the multidrug-resistant cells, immunological and functional studies revealed only a minor increase in the expression of a hexose transporter-like protein in resistant versus drug-sensitive cells. Taken together, these results suggest the participation of the mammalian facilitative glucose transporter in the development of drug resistance.
Mol Cell Biol 1991 Jul
PMID:A possible role for a mammalian facilitative hexose transporter in the development of resistance to drugs. 167 25

We report the functional expression of the mammalian muscle-adipocyte insulin-sensitive hexose transporter in Xenopus laevis oocytes. Oocytes microinjected with RNA synthesized in vitro showed enhanced hexose transport activity compared with uninjected controls. However, like the endogenous oocyte hexose transporter, activity was stimulated only twofold by 1 microM insulin. X. laevis oocytes injected with in vitro-synthesized RNA encoding the human insulin proreceptor expressed a functionally active insulin receptor that enhanced the insulin sensitivity of injected oocytes. This increase was not observed in oocytes expressing a mutant insulin receptor that lacked protein tyrosine kinase activity. In the presence of the coexpressed human insulin receptor, insulin induced a two- to threefold increase in hexose transport. The muscle-, brain-, and liver-type hexose carriers normally expressed in tissues with different responses to insulin exhibited the same insulin sensitivity when expressed in oocytes. This was observed whether or not the insulin signal was transduced through a coexpressed human insulin receptor or the endogenous oocyte insulin-like growth factor I receptor. We conclude that the expressed human insulin receptor is able to couple efficiently with preexisting postreceptor regulatory pathways in oocytes and that the regulation of hexose transport in these cells can be mediated through the combined actions of the expressed human insulin receptor and the endogenous oocyte insulin-like growth factor I receptor.
Mol Cell Biol 1990 Feb
PMID:Reconstitution of an insulin signaling pathway in Xenopus laevis oocytes: coexpression of a mammalian insulin receptor and three different mammalian hexose transporters. 168 99

Hep G2 cells were used to study the early sequence of events regulating production of insulin-like growth factor-binding protein-1 (IGFBP-1). Cytochalasin B (100 microM) specifically inhibited 2-deoxyglucose uptake by Hep G2 cells and stimulated IGFBP-1 production 2-fold. Insulin (300 nM) did not stimulate hexose uptake but inhibited IGFBP-1 production more than 50%. A change in IGFBP-1 secretion was observed as early as 2 h after a 15-min or 2-h pulse exposure to either effector. In contrast to IGFBP-1, albumin production was diminished in the presence of cytochalasin B and increased by insulin. From these results we conclude that IGFBP-1 synthesis is (i) stimulated by transient inhibition of cellular glucose uptake and further stimulated by long-term glucose deprivation, and (ii) inhibited by transient exposure to insulin with further inhibition on long-term exposure. These effects are consistent with the dynamic regulation of IGFBP-1 by nutritional status.
Mol Cell Endocrinol 1991 May
PMID:Cytochalasin B stimulates insulin-like growth factor-binding protein-1 production by Hep G2 cells. 172 53

In rat pancreatic islets, a rise in extracellular D-glucose concentration is known to cause a greater increase in the oxidation of D-[6-14C]glucose than utilization of D-[5-3H]glucose. In the present study, such a preferential stimulation of acetyl residue oxidation relative to glycolytic flux was mimicked by nutrient secretagogues such as 2-aminobicyclo[2,2,1]heptane-2-carboxylate, 3-phenylpyruvate, L-leucine, 2-ketoisocaproate, D-fructose and ketone bodies. The preferential stimulation of D-[6-14C]glucose oxidation by these nutrients was observed at all hexose concentrations (0.5, 6.0 and 16.7 mM), coincided with an unaltered rate of D-[3,4-14C]glucose oxidation, was impaired in the absence of extracellular Ca2+, and failed to be affected by NH4+. Although the ratio between D-[6-14C]glucose oxidation and D-[5-3H]glucose utilization in islets exposed to other nutrient secretagogues could be affected by factors such as isotopic dilution and mitochondrial redox state, the present data afford strong support to the view that the preferential stimulation of oxidative events in the Krebs cycle of nutrient-stimulated islets is linked to the activation of key mitochondrial dehydrogenases, e.g. 2-ketoglutarate dehydrogenase. The latter activation might result from the mitochondrial accumulation of Ca2+, as attributable not solely to stimulation of Ca2+ inflow into the islet cells but also to an increase in ATP availability.
Mol Cell Biochem 1991 Oct 16
PMID:Hexose metabolism in pancreatic islets. Activation of the Krebs cycle by nutrient secretagogues. 179 28

In rat pancreatic islets, a rise in D-glucose concentrations increases the oxidation of hexose-derived acetyl residues relative to glycolytic flux, an effect possibly attributable, in part at least, to the activation of key mitochondrial dehydrogenases by Ca2+ accumulated in the mitochondria of glucose-stimulated islet cells. The effects of non-nutrient insulinotropic agents upon D-[6-14C]glucose oxidation and D-[5-3H]glucose utilization were investigated. At an intermediate concentration of D-glucose (6 mM), the oxidation of D-[6-14C]glucose was unaffected by hypoglycemic sulfonylureas, an organic Ca2+ agonist, a cholinergic agent, forskolin, theophylline and cytochalasin B. At a higher concentration of the hexose (17 mM), however, the 14CO2/3H2O production rate was decreased by organic and inorganic Ca(2+)-antagonists and by ouabain, whilst being increased by NH+4 (10 mM) and aminooxyacetate. These findings suggest that the preferential stimulation of oxidative events in the Krebs cycle is largely independent of the rate of insulin release, and not merely consequential to the stimulation of Ca2+ inflow into the B-cell. It might be regulated, in a feedback process, by the rate of ATP utilization and, both directly and indirectly, by the mitochondrial redox state. The glucose-induced mitochondrial accumulation of Ca2+ and subsequent activation of the Krebs cycle appear to require an increase in both cytosolic Ca2+ activity and ATP availability.
Mol Cell Endocrinol 1991 Apr
PMID:Hexose metabolism in pancreatic islets. Regulation of D-[6-14C]glucose oxidation by non-nutrient secretagogues. 182 Sep 66


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