Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe hepatic damage with submassive necrosis induced in rats by an intraperitoneal injection of a single dose of galactosamine hydrochloride was studied. In the severely damaged liver, the remarkable decreases of glycogen and UDPG in the damaged liver were seen. This means extreme decrease in the reserve power of glycolysis. Moreover, the activities of glucose-6-phosphatase and fructose-1,6-diphosphatase decreased. Therefore, the glucose release from liver into the blood stream decreases and the inhibition of gluconeogenesis occurs. In the damaged liver, the decrease of UTP which is essential for the synthesis of sugar moiety of polysaccharide, was seen. Further, the activities of L-glutamine: D-fructose-6-phosphate amidotransferase and UDP N-acetylglucosamine 2'-epimerase which are two key enzymes of polysaccharide synthesizing enzyme were seen to decrease remarkably. In the damaged liver, the glycoprotein fraction decreased more strikingly than the acid mucopolysaccharide fraction. Moreover, the decrease of fructose-1,6-diphosphatase activity seems also to effect on the inhibition of polysaccharide synthesis. In these respects, in the severe hepatic damage, the synthesis of glycoprotein which is essential for liver cell seems to be inhibited.
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PMID:Studies on severe hepatic damage induced by galactosamine. 617 14

To study the relationship between the dose of phenobarbital (PB) and the magnitude of its effects on microsomal enzymes, cytochrome P-450, UDP-glucuronyl transferase (UDPGT), and glucose-6-phosphatase (G6P) activities were determined in liver homogenate and microsome preparations from control rats and rats treated for 6 days with PB at doses ranging from 1 to 125 mg/kg/day. Both P-450 and UDPGT activities were enhanced by PB in a dose-related fashion. However, while the lowest dose of the drug to produce significant induction of both enzymes was the same (3 mg/kg), maximal induction of P-450 (214%) and UDPGT (285%) was obtained with different doses of PB, namely 75 and 125 mg/kg, respectively. UDPGT induction could equally be demonstrated regardless of whether "native" enzyme or enzyme activated by UDP-N-acetyl glucosamine, digitonin or deoxycholate was employed. In contrast to these inducing effects of the drug on P-450 and UDPGT, PB treatment resulted in a dose-related inhibition of G6P activity. The inhibitory effect was observed with both "native" and deoxycholate-activated enzymes, and could be demonstrated whether the data were expressed as enzyme specific activity (nanomoles per minute per milligram microsomal protein) or as total G6P activity (micromoles per minute per 100 g body weight). These results indicate that: (I) enzyme induction by PB is dose-related; (ii) induction of both P-450 and UDPGT is obtained in the rat with doses of the drug similar to those given to man; and (iii) observed inhibition of G6P activity by PB does not solely reflect an enzymatic dilution secondary to the proliferated endoplasmic reticulum.
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PMID:Dose-related effects of phenobarbital on hepatic microsomal enzymes. 631 41

The activities of various enzymes involved in detoxication and carbohydrate metabolism in the liver and the gastrointestinal tract of germfree (GF) and conventional (CV) rats, 8 and 40 weeks' old, were measured in relationship to intestinal microflora and aging. In 8-week-old rats, the activities of nitroreductase (NR) and aniline hydroxylase (AH) in the liver, and of alkaline phosphatase (ALP), maltase and lactase in the duodenum were higher in GF than in CV rats, but the activities of arginosuccinate synthetase (ASS) and lactate dehydrogenase (LDH) in the liver were higher in CV than in GF rats. In 40-week-old rats, the activities of NR and glucose-6-phosphatase dehydrogenase (G-6-PDH) of the liver and ALP, maltase and lactase of the duodenum were higher in GF than in CV rats, but those of ASS, UDP-glucuronyl transferase (UDP-GT), AH, beta-glucuronidase, and LDH of the liver were higher in CV than in GF rats. Compared between 8- and 40-week-old rats the activities of NR, beta-glucuronidase, LDH, and acid phosphatase increased with aging in both GF and CV rats. The specific activities of ASS in CV and UDP-GT and AH in GF rats decreased with aging. The total activities of ASS and AH in GF rats also decreased with aging. The activities of ALP, maltase and lactase decreased with aging in both GF and CV rats. Thus, these data suggested that there are influences of indigenous intestinal microflora and aging on the activities of various enzymes in the liver and gastrointestinal tract.
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PMID:Intestinal microflora and aging: age-related change of enzymes in the liver and the small intestine of germ-free and conventional rats. 679 85

Measurement of hepatic glucose production (HGP) by standard isotope dilution reveals only the net release of glucose from the liver, not the flux across glucose-6-phosphatase ([G6Pase] or total hepatic glucose output), hepatic glucose cycling (HGC), irreversible glucose disposal into glycogen in the liver (hepatic Rd), or net hepatic glucose balance. We describe two independent isotopic techniques for measuring these parameters in vivo, both of which use secreted glucuronate (GlcUA). HGC can be quantified by measuring a correction factor for glucose label retained in hepatic glucose-6-phosphate (G6P), sampled as GlcUA. A complementary technique for measuring total hepatic glucose output is also described (reverse dilution), requiring administration of no labeled glucose but instead a labeled gluconeogenic precursor and unlabeled glucose. Hepatic Rd is calculated by multiplying the rate of appearance (Ra) of hepatic UDP-glucose ([UDP-glc] based on dilution of labeled galactose in GlcUA) times the direct entry of glucose into hepatic UDP-glc and the fraction of labeled UDP-glc retained in the liver. The sum of hepatic Rd plus HGC represents the total hepatic glucose phosphorylation rate. Rats received intravenous (i.v.) glucose infusions at a rate of 15 to 30 mg/kg/min after a 24-hour fast. Despite a suppression of net HGP more than 50%, total hepatic glucose output was not significantly decreased, because of increased HGC. Total hepatic glucose output calculated by reverse dilution yielded similar results during i.v. glucose infusions at 15 mg/kg/min, although values were higher than obtained by the correction-factor method at 30 mg/kg/min. The fraction of labeled UDP-glc released into blood glucose, representing a hepatic glycogen cycle, decreased from 35% (fasted) to nearly 0% (i.v. glucose 30 mg/kg/min). Hepatic Rd was 1.4, 4.6, and 7.5 mg/kg/min (fasted and i.v. glucose 15 and 30 mg/kg/min, respectively); total hepatic glucose phosphorylation increased substantially (from 4.2 to 8.5 to 12.7 mg/kg/min) and net hepatic glucose balance changed from negative to positive during i.v. glucose. In conclusion, hepatic G6Pase flux, glucose phosphorylation, HGC, disposal of glucose into glycogen, and net glucose balance can be measured noninvasively in vivo under various metabolic conditions by techniques involving the GlcUA probe.
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PMID:Hepatic glucose-6-phosphatase flux and glucose phosphorylation, cycling, irreversible disposal, and net balance in vivo in rats. Measurement using the secreted glucuronate technique. 943 32

Using insulin-secreting cells, we previously demonstrated that specific proteins associated with the cytosolic, secretory granule, and mitochondrial fractions undergo a novel type of phosphorylation on their histidine residues. Subsequently, we identified these proteins as the nucleoside diphosphate kinase (NDPK) [Kowluru and Metz, Biochemistry 1994;33:12495-503], the beta subunit of trimeric GTP-binding proteins [Kowluru et al., Biochem J 1996;313:97-107], and the alpha subunit of succinyl-CoA synthetase [Kowluru, Diabetologia 2001;44:89-94], respectively. Since several other enzymes of intermediary metabolism (e.g. ATP-citrate lyase and glucose-6-phosphatase) also undergo histidine phosphorylation, these initial findings may have a more generalized significance to beta cells. Herein, we characterized a novel protein histidine kinase in pancreatic beta cells, and determined it to be acid- and heat-labile as well as alkali-resistant in its phosphorylation of histone 4. Such an activity was detected in normal rat islets, human islets, and clonal beta (HIT-T15 and INS-1) cells, and could utilize either ATP or GTP as a phosphoryl donor (with K(m) values in the range of 60-100 microM). On a size-exclusion column, its molecular mass was estimated to be in the range of 60-70 kDa. It was stimulated by divalent cations (Mg(2+)>Mn(2+)>control=Ca(2+)=Zn(2+)=Co(2+)), but was resistant to polyamines. It was inactivated by known in vitro inhibitors of protein histidine phosphorylation (e.g. UDP or cromoglycate). Mastoparan, a global activator of G-proteins and insulin secretion from isolated beta cells, but not mastoparan-17, its inactive analog, stimulated histidine kinase activity and histidine phosphorylation of G(beta) subunit and insulin secretion from isolated rat islets. These studies identify, for the first time, a protein kinase activity in the pancreatic beta cell that does not act on traditional -Ser, -Tyr, or -Thr residues. They also establish a possible link between histidine kinase activity and G(beta) phosphorylation in isolated beta cells.
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PMID:Identification and characterization of a novel protein histidine kinase in the islet beta cell: evidence for its regulation by mastoparan, an activator of G-proteins and insulin secretion. 1211 Mar 68


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