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)

To elucidate the causes of changes of carbohydrate metabolic pathways, the time course of utilization of dietary [U-14C]sucrose and induction of enzyme activities in the livers of rats were investigated. Adult male rats of BHE strain were refed after a fast of 2 days. The nutritionally complete refeeding diet contained 60% sucrose as the only source of carbohydrate. [U-14C]Sucrose was included in the diet on either day 1 or day 2, or both of refeeding. During the first day of refeeding, the radioactivity was incorporated mainly into liver glycogen which rose to over 100 mg/g. During the second day, little 14C appeared in the liver glycogen, which decreased sharply while glucose-6-phosphatase activity increased. The glycogenic pathway thus appeared to be blocked. On the other hand, 14C incorporation in the liver fat was minimal during the first day, but was quite extensive during the second day of refeeding. The enhanced lipogenesis was accompanied by large increases of activities of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and NADP-malic dehydrogenase. Results clearly indicate that the carbohydrate load in the liver of intact animals was initially metabolized by the glycogenic pathway. When glycogenesis stopped, carbohydrate was metabolized differently. The enhanced incorporation of [U-14C]sucrose into liver lipids indicates an increased formation of acetyl CoA and an accelerated formation and use of NADPH, probably from increasing dehydrogenase activities. Our data suggest that the blockage of synthesis of glycogen with the continuation of carbohydrate load was a primary cause in over-shooting induction of hepatic dehydrogenase activities and lipogenesis.
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PMID:Stoppage of glycogenesis and "over-shoot" of induction of lipogenesis and its related enzyme activities in the liver of fasted-refed rats. 17 17

1. The relationships between food intake self-selection and liver substrates (glycogen, fat) or activities of pyruvate kinase, glucose-6-phosphate dehydrogenase, malic enzyme, acetyl CoA carboxylase, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase were determined during the spontaneous variations of body weight in the dormouse. 2. The results show that during the phase of increasing body weight, carbohydrate intake and enzyme activities involved in lipogenesis are on a high level. 3. On the last part of the body weight increasing phase, when lipid intake occurs, lipogenesis is depressed and a gluconeogenetic activity is set on, while total caloric intake is important and body weight is still increasing. 4. These metabolic changes are interpreted as a preparation to hibernating conditions in the dormouse.
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PMID:Relationships between spontaneous food intake and metabolic activities in the dormouse (Glis glis L.). 31 73

2-Bromopalmitate and 2-bromopalmitoyl-CoA have been shown to inhibit a variety of enzymes and proteins associated with lipid metabolism. We found that both of the brominated compounds were non-competitive inhibitors of two microsomal activities of triacylglycerol biosynthesis, the mono- and diacylglycerol acyltransferases. With both compounds, the calculated Ki values were lower than the Km value for the palmitoyl-CoA substrate. In addition to inhibiting two other lipid synthetic activities, fatty acid CoA ligase and glycerol-3-P acyltransferase, 2-bromopalmitate and 2-bromopalmitoyl-CoA also inhibited two microsomal enzyme activities that are not related to lipid metabolism, NADPH cytochrome-c reductase and glucose-6-phosphatase. Inhibition of the three acyltransferases and fatty acid CoA ligase could be overcome by the addition of phospholipid vesicles, and 2-bromo[14C]palmitate readily labeled a large number of membrane-bound proteins as well as cytosolic proteins that had been solubilized in SDS. Thus, it appears likely that the inhibitory properties of the brominated compounds strongly depend on the effective concentration of the inhibitor within membranes rather than on any specific affinity for an acyl-chain binding region of the enzyme.
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PMID:2-Bromopalmitoyl-CoA and 2-bromopalmitate: promiscuous inhibitors of membrane-bound enzymes. 157 64

In order to find the markers of the toxicity of the autoxidized lipids in the liver, rats were given a lethal amount of secondary autoxidation products of linoleic acid (400 mg/rat/day for 3 days) and then changes in the hepatic metabolic functions were analyzed. A decrease in acetyl-CoA level to half caused by the depletion of CoASH was reported in an associated paper (J. Nutr. Sci. Vitaminol., 35, 11-23, 1989). Citrate, isocitrate, and 2-oxoglutarate also decreased to half the level of those of the control group. Reduction in isocitrate dehydrogenase activity was only 25%, while NADH2 and ATP levels remained unchanged. Thus, the reduction in the citrate cycle activity was due to the decrease in acetyl-CoA. The activity of mitochondrial succinate dehydrogenase was decreased to 1/5. Other appreciable changes were depletion of glucose 6-phosphate and fructose 6-phosphate, accumulation of glucose 1-phosphate, reductions in hexokinase, phosphofructokinase, glucose-6-phosphatase, phosphoglucomutase, and phosphogluconate dehydrogenase activities, and decrease in the NADPH2 level. It was considered that these changes were caused by the depletion of glucose 6-phosphate whose synthetic pathways were abnormal. Therefore, the markers of the hepatotoxicity of secondary products were the changes in the CoASH level and the activities of succinate dehydrogenase and synthetic pathways for glucose 6-phosphate.
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PMID:Succinate dehydrogenase and synthetic pathways of glucose 6-phosphate are also the markers of the toxicity of orally administered secondary autoxidation products of linoleic acid in rat liver. 254 8

The saturation of the fat contained in the diet has been observed to affect the acylcoenzyme A:cholesterol acyltransferase (ACAT) activity of rat liver microsomes. ACAT activity in microsomes (Mp) prepared from livers of rats fed a polyunsaturated fat-enriched diet containing 14% sunflower seed oil was 70-90% higher than in microsomes (Ms) prepared from livers of rats fed a saturated fat-enriched diet containing 14% coconut oil. This difference was observed within 20 days after the diets were begun, the earliest time tested, and persisted throughout the 70-day experimental period. The difference was noted at all [1-14C]palmitoyl CoA concentrations tested, 2.5-33 micronM, and at temperatures between 18 and 40 degrees C. Arrhenius plots revealed a single transition in enzyme activity, occurring at 29 degrees C in both microsomal preparations. Likewise, the activation energy above this transition was the same in Mp and Ms, 12.5 KCal/mol. Addition of albumin to the incubation medium increased the ACAT activity of both microsome preparations, but the difference between Mp and Ms persisted. Mp was enriched in polyenoic fatty acids, primarily 18:2 and 20:4, while Ms was enriched in monoenoic acids. Although the 20:4 increase in Mp occurred in all phosphoglycerides, it was especially pronounced in the serine and inositol phosphoglyceride fraction. There were no differences in the phospholipid or cholesterol content, phospholipid head group composition, or protein composition of the two microsomal preparations. The possibility is discussed that the changes in ACAT activity result from the differences in fatty acid composition of the microsomes. Other microsomal enzymes exhibited varying responses to these dietary fatty acid modifications. Palmitoyl CoA hydrolase and NADPH cytochrome c reductase activities were unchanged. UDP glucuronyl transferase activity was 50% higher in Mp, but glucose-6-phosphatase and NADH cytochrome b5 reductase activities were 25% higher in Ms. Therefore, dietary fat modifications do not produce a uniform effect on the activity of microsomal enzymes.
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PMID:Effect of dietary fat saturation on acylcoenzyme A:cholesterol acyltransferase activity of rat liver microsomes. 610 16

The subcellular localization of glutamine synthetase, an enzyme fundamental to the compartmentation of glutamate hypothesis, was investigated using brain tissue of adult rats. The distribution of this enzyme in relation to the distribution of glucose-6-phosphatase, glutamate dehydrogenase and acetycholine esterase was studied using a fractionation scheme which had been previously extensively characterized in terms of intramitochondrial enzyme complements. Glutamine synthetase was found to be predominantly localized at the nerve terminal and a number of results suggested a possibble association with the synaptic membrane. The observations are discussed in relation to the compartmentation of glutamate metabolism. Acetate and ammonia are precursors of the 'small' pool of glutamate from which most of the synthesis of glutamine occurs. Since one population of synaptic mitochondria has previously been shown to be enriched in glutamate dehydrogenase and acetyl CoA synthetase and in view of the current observtions that synaptosomes are probably in association with a large proportion of brain glutamine synthetase, it is tentatively suggested that the synaptic complex represents at least in part the site of the 'small' glutamate pool.
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PMID:The distribution of glutamine synthetase in subcellular fractions of rat brain. 610 1

The topography of phosphatidylcholine, phosphatidylethanolamine and triacylglycerol biosynthetic enzymes within the transverse plane of rat liver microsomes was investigated using two impermeant inhibitors, mercury-dextran and dextran-maleimide. Between 70 and 98% of the activities of fatty acid : CoA ligase (EC 6.2.1.3), sn-glycerol-3-phosphate acyltransferase (EC 2.3.1.15), phosphatidic acid phosphatase (EC 3.1.3.4), diacylglycerol acyltransferase (EC 2.3.1.20), diacylglycerol cholinephosphotransferase (EC 2.7.8.2) and diacylglycerol ethanolaminephosphotransferase (EC 2.7.8.1) were inactivated by mercury-dextran. Dextran-maleimide caused 52% inactivation of the sn-glycerol-3-phosphate acyltransferase. Inactivation of each of these activities except fatty acid : CoA ligase occurred in microsomal vesicles which remained intact as evidenced by the maintenance of highly latent mannose-6-phosphatase activity (EC 3.1.3.9). These glycerolipid biosynthetic activities were not latent, indicating that substrates have free access to the active sites. Moreover, ATP, CDP-choline and CMP appeared unable to penetrate the microsome membrane. These data indicate that the active sites of thease enzymes are located on the external surface of microsomal vesicles. It is concluded that the biosynthesis of phosphatidylcholine, phosphatidylethanolamine and triacylglycerol occurs asymmetrically on the cytoplasmic surface of the endoplasmic reticulum.
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PMID:Topography of phosphatidylcholine, phosphatidylethanolamine and triacylgycerol biosynthetic enzymes in rat liver microsomes. 615 20

1. The development of rat liver acyl-CoA:sn-glycerol-3-phosphate-O-acyl-transferase (EC 2.3.1.15) is characterized by an increase and decrease in activity during the neonatal period, followed by a second increase and decrease during the late weaning period. Kidney acyltransferase exhibits a similar peak in activity during the neonatal period before increasing to adult levels of activity during the late weaning period. 2. Nucleosidediphosphatase activity increases rapidly during the neonatal period and thereafter gradually rises to adult levels in both liver and kidney. The latency of the enzyme increases rapidly after birth and thereafter shows little change with age. The enzyme appears to be more latent in the liver than in the kidney at all ages studied. 3. NADPH-cytochrome c reductase of liver has a single steep maximum and minimum in activity during the neonatal period, before increasing again to adult levels during the late weaning period. The enzyme in kidney shows a similar developmental pattern but at much lower levels of specific activity. 4. sn-Glycerol-3-phosphate acyltransferase activity was significantly higher in rough than in smooth membranes throughout the neonatal period of rapid smooth membrane proliferation. This distribution of enzyme activity is unlike that reported by others in phenobarbital-induced smooth membrane proliferation and suggests a major role for rough membranes in phospholipid synthesis during the neonatal period. 5. The qualitative similarity in development in rough and smooth microsomal subfractions for each of these enzymes is in distinct contrast with results previously reported for glucose-6-phosphatase.
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PMID:Postnatal development of some membrane-bound enzymes of rat liver and kidney. 626 Feb 25

1,2-Diacyl-sn-glycerol : CDPcholine cholinephosphotransferase (EC 2.7.8.2) and acyl-CoA : 1-acyl-sn-glycero-3-phosphocholine acyltransferase (EC 2.3.1.23) activities of rat liver microsomes can be inhibited by centrophenoxine (N,N-dimethylaminoethyl p-chlorophenoxyacetate). This inhibition is brought about by the intact centrophenoxine molecule rather than by the products of hydrolysis. A nonhydrolyzable ether analog of centrophenoxine was synthesized (neophenoxine; N,N-dimethylaminoethyl p-chlorophenoxyethyl ether) and proved most effective in inhibiting the two routes of phosphatidylcholine biosynthesis. While 50% inhibition of the cholinephosphotransferase was attained at 5 mM neophenoxine, 50% inhibition of the acyltransferase required 0.6 mM neophenoxine levels only. Inhibition of the cholinephosphotransferase (Ki approximately 1.5 mM) and the acyltransferase (Ki approximately 1 mM) by neophenoxine was shown to be noncompetitive. Other membrane-bound enzymes, such as glucose-6-phosphatase, monoacylglycerol lipase, alkaline phosphatase or phospholipase A2 were not affected by the inhibitors. Because of this specificity, and because of the high affinity of the microsomal membrane for such agents, centrophenoxine and neophenoxine should prove useful for controlling phosphatidylcholine synthesis and for modulating the phosphatidylcholine deacylation-reacylation cycle.
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PMID:Modulation of phosphatidylcholine synthesis in vitro. Inhibition of diacylglycerol cholinephosphotransferase and lysophosphatidylcholine acyltransferase by centrophenoxine and neophenoxine. 626 46

In native rat liver microsomes glucose 6-phosphatase activity is dependent not only on the activity of the glucose-6-phosphatase enzyme (which is lumenal) but also on the transport of glucose-6-phosphate, phosphate and glucose through the respective translocases T1, T2 and T3. By using enzymic assay techniques, palmitoyl-CoA or CoA was found to inhibit glucose-6-phosphatase activity in intact microsomes. The effect of CoA required ATP and fatty acids to form fatty acyl esters. Increasing concentrations (2-50 microM) of CoA (plus ATP and 20 microM added palmitic acid) or of palmitoyl-CoA progressively decreased glucose-6-phosphatase activity to 50% of the control value. The inhibition lowered the Vmax without significantly changing the Km. A non-hydrolysable analogue of palmitoyl-CoA also inhibited, demonstrating that binding of palmitoyl-CoA rather than hydrolysis produces the inhibition. Light-scattering measurements of osmotically induced changes in the size of rat liver microsomal vesicles pre-equilibrated in a low-osmolality buffer demonstrated that palmitoyl-CoA alone or CoA plus ATP and palmitic acid altered the microsomal permeability to glucose 6-phosphate, but not to glucose or phosphate, indicating that T1 is the site of palmitoyl-CoA binding and inhibition of glucose-6-phosphatase activity in native microsomes. The type of inhibition found suggests that liver microsomes may comprise vesicles heterogeneous with respect to glucose-6-phosphate translocase(s), i.e. sensitive or insensitive to fatty acid ester inhibition.
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PMID:Fatty acyl-CoA esters inhibit glucose-6-phosphatase in rat liver microsomes. 773 74


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