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)

We have proposed that glucose-6-phosphatase (EC 3.1.3.9) is a two-component system consisting of (a) a glucose-6-P-specific transporter which mediates the movement of the hexose phosphate from the cytosol to the lumen of the endoplasmic reticulum (or cisternae of the isolated microsomal vesicle), and (b) a nonspecific phosphohydrolase-phosphotransferase localized on the luminal surface of the membrane (Arion, W.J., Wallin, B.K., Lange, A.J., and Ballas, L.M. (1975) Mol. Cell. Biochem. 6, 75-83). Additional support for this model has been obtained by studying the interactions of D-mannose-6-P and D-mannose with the enzyme of untreated (i.e. intact) and taurocholate-disrupted microsomes. An exact correspondence was shown between the mannose-6-P phosphohydrolase activity at low substrate concentrations and the permeability of the microsomal membrane to EDTA. The state of intactness of the membrane influenced the kinetics of mannose inhibition of glucose-6-P hydrolysis; uncompetitive and noncompetitive inhibitions were observed for intact and disrupted microsomes, respectively. The apparent Km for glucose-6-P was smaller with intact preparations at mannose concentrations above 0.3 M. Mannose significantly inhibited total glucose-6-P utilization by intact microsomes, whereas D-glucose had a stimulatory effect. Both hexoses markedly enhanced the rate of glucose-6-P utilization by disrupted microsomes. The actions of mannose on the glucose-6-phosphatase of intact microsomes fully support the postulated transport model. They are predictable consequences of the synthesis and accumulation of mannose-6-P in the cisternae of microsomal vesicles which possess a nonspecific, multifunctional enzyme on the inner surface and a limiting membrane permeable to D-glucose, D-mannose, glucose-6-P, but impermeable to mannose-6-P. The latency of the mannose-6-P phosphohydrolase activity is proposed as a reliable, quantitative index of microsomal membrane integrity. The inherent limitations of the use of EDTA permeability for this purpose are discussed.
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PMID:Microsomal membrane permeability and the hepatic glucose-6-phosphatase system. Interactions of the system with D-mannose 6-phosphate and D-mannose. 18 83

Iodoacetamide, N-ethylmaleimide, p-hydroxymercuribenzoate (p-MB) and HgCl2 were tested as inhibitors of microsomal glucose-6-phosphatase. Iodoacetamide had no effect at 2 mM. N-ethylmaleimide inhibited only crude, but not purified microsomal preparations (M2) or crude microsomes exposed to deoxycholate. 14C-labelled N-ethylmaleimide was not bound by the M2 protein fraction. p-MB inhibited all types of preparations and the inhibition was not counteracted by detergent. A more detailed study was carried out with the purified M2 fraction (specific activity: 2-4 mumoles Pi/min/mg protein). Glucose-6-phosphate hydrolysis was inhibited 50% by 5 X 10(-5) M p-MB. The inhibition was completely reversible by dithiothreitol except when the enzyme was pre-incubated with p-MB in the absence of substrate. Then p-MB accelerated the temperature-dependent inactivation of glucose-6-phosphatase. Binding studies showed that around 3 mumoles 14C-p-MB were incorporated into 100 mg M2 protein regardless of the concentration of mercurial in the incubation mixture. That is, over a 25 fold range of p-MB concentration, causing up to 80% inhibition of enzyme activity, no difference was seen in the amount of labelled p-MB which was irreversibly bound to M2 protein. Kinetically p-MB behaved like a reversible inhibitor and this was confirmed by dilution experiments. Several compounds, including some amino acids, antagonized the inhibition by p-MB. The order of effectiveness was EDTA greater than barbital greater than tryptophan greater than histidine greater than lysine greater than other amino acids. Glycine, Tris and urea were ineffective competitors of p-MB inhibition. Double reciprocal plots showed that the Km for glucose-6-phosphate was increased and the Vmax reduced in the presence of p-MB. HgCl2 was a more effective inhibitor than p-MB with a Ki of 6 X 10(-6) M. We conclude that a reaction of p-MB with M2 sulfhydryls does not play a part in the inhibition of enzyme activity. It is suggested that p-MB may interact with one or more amino acid side chains in such a way that enzyme conformation is altered.
Mol Cell Biochem 1976 Jul 30
PMID:The effect of p-hydroxymercuribenzoate and congeners on microsomal glucose-6-phosphatase. 18 75

Pregnenolone and progesterone concentrated in the microsomal fraction of cryptorchid mouse testis compared with mitochondria and cytosol. While the concentrating mechanisms had high capacity and low association constants the effect did not seem to be due to nonspecific solubility in the lipid components since 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione and testosterone did not show differential concentration. Also digestion with phospholipases A2 and C to the point where most of the phospholipids were specifically split, only lowered the differential binding of pregnenolone and progesterone by less than half. Trypsin had a greater effect, short digestion at 0 degrees C lowering the specific binding to 35-40% and decreasing the steroid dehydrogenases to a similar extent. The members of the mixed function oxidase system in the testis microsomes were particularly sensitive to trypsin, cytochrome P-450 and, as a consequence, 17alpha-hydroxylase and 17, 20-lyase activity being eliminated under tha same conditions while liver microsomal cytochrome P-450 was hardly affected. Bonds split by trypsin seem to play a more important role in the hydroxylase activity of testis microsomes than in the hepatic system.
Mol Cell Endocrinol 1976 Dec
PMID:Effects of trypsin and phospholipases A2 and C on enzyme organization in testis microsomes. 18 6

The interaction between the plant lectin concanavalin A (Con A) and hepatic receptors for human growth hormone (GH) has been studied in particulate and soluble microsomal membrane preparations from rabbit and rat liver. Con A shows a dose-dependent, partial (30%) inhibition of 125I-human GH binding which is reversed by the Con A competitor, alpha-methyl mannoside. The Con A effect is dependent on the receptor concentration. The inhibition by Con A in rabbit liver is a reflection of a decreased number of available binding sites--there is no effect on binding affinity. It would appear that Con A binds directly to the GH-binding protein and not to an adjacent membrane glycoprotein. The GH receptor may consist of more than one molecular species, differing only in the carbohydrate type or content.
Mol Cell Endocrinol 1979 Nov
PMID:Interaction between the hepatic growth hormone receptor and concanavalin A. 22 48

A model for microsomal glucose 6-phosphatase (EC 3.1.3.9) is presented. Glucose 6-phosphatase is postulated to be resultant of the coupling of two components of the microsomal membrane: 1) a glucose 6-phosphate - specific transport system which functions to shuttle the sugar phosphate from the cytoplasm to the lumen of the endoplasmic reticulum; and 2) a catalytic component, glucose-6-P phosphohydrolase, bound to the luminal surface of the membrane. A large body of existing data was shown to be consistent with this hypothesis. In particular, the model reconciles well-documented differences in the kinetic properties of the enzyme of untreated and modified microsomal preparations. Characteristic responses of the enzyme to changes in nutritional and hormonal states may be attributed to adaptations which alter the relative capacities of the transport and catalytic components.
Mol Cell Biochem 1975 Feb 28
PMID:On the involvement of a glucose 6-phosphate transport system in the function of microsomal glucose 6-phosphatase. 23 36

1. Marker enzymes for the principal subcellular organelles of rat liver were asayed in the liver of rats 1 day and 8 days after bile-duct ligation or after laparotomy as a control procedure. 2. The microsomal enzymes in liver tissue showed complex changes. Benz[alpha]pyrene hydroxylase activity, predominantly found in the smooth endoplasmic reticulum, was decreased. Glucose 6-phosphatase activity and ribonucleic acid, which are localized predominantly in the rough endoplasmic reticulum, were increased. 3. The plasma membrane enzyme, alkaline phosphatase, increased in activity after bile-duct ligation. 4. No changes in mitochondrial enzyme activities were noted after 1 day but there was a 50% reduction 8 days after ligation. Lysosomal enzyme activities did not change in the liver tissue. 5. Liver catalase and D-amino acid oxidase activities showed a slight increase at 1 day postligation but a significant fall by 8 days. 6. Lactate dehydrogenase, a cytosol enzyme, showed a decrease in activity after 1 day but an increase in tissue activities 8 days after ligation. 7. Serum activities of mitochondrial, plasma membrane, microsomal, lysosomal and cytosol marker enzymes tended to increase post-ligation, particularly at 8 days. 8. Monoamine oxidase, a predominantly mitochondrial enzyme, was greatly elevated in the serum after 1 day but had returned to normal activities by 8 days.
Clin Sci Mol Med 1975 Apr
PMID:Effect of bile-duct ligation on organelle marker enzymes in the liver and serum of rats. 23 11

The incorporation of [3H]-glucosamine into polypeptides of three fractions of polysomes in MPC-11 cells was studied. After short term incubation greatest incorporation was observed in a fraction of membrane-bound polysomes, which after nitrogen cavitation of cells, remained bound to the endoplasmic reticulum (ER) associated with the nucleus (fraction 2). Polypeptide chains on membrane-bound polysomes in the microsomal fraction (fraction 1) and free polysomes contained much less radioactivity. Since nascent polypeptide chains contained within membrane-bound polysomes of fraction 2 are glycosylated at an earlier stage than those in fraction 1 it is likely that this represents a difference in type of proteins synthesized in the respective fractions of ER.
Mol Biol Rep 1979 Feb 15
PMID:Differences in the incorporation of [3H]-glucosamine into nascent polypeptide chains on free polysomes and two fractions of membrane-bound polysomes in mouse myeloma cells. 44 Mar 1

Fluid mixed solvents appear to supply an effective tool for investigation of enzyme catalysis at subzero temperatures. Labile reaction intermediates may be stabilized, characterized and separated. Cycling of reaction processes and side reactions can be slowed or stopped to permit single turnover of individual molecular events, and kinetic response to temperature and other physical parameters can provide dynamic and thermodynamic analysis of single enzyme systems. Multienzyme systems can furnish reliable probes of potential, limitations and possible procedural artefacts of the method. Amply explored examples are supplied by the studies of two components of the soluble camphor hydroxylase and the hepatic R450LM2 in solution and in the subcellular microsomal organelles, to reveal labile single enzyme compounds and multienzyme processes.
Mol Cell Biochem 1979 Jul 15
PMID:Testing cosolvent cryoenzymology on multi-enzyme systems. 49 56

The subcellular localization and characterization of some of the components involved in the glycosylation of asparagine type glycoproteins was attempted using dolichyl diphosphate [14C]mannose oligosaccharide as precursor of the glycosylation reaction in vitro. Isolated rough and smooth microsomal fractions were able to carry out the transfer of the carbohydrate moiety from lipid oligosaccharide to endogenous protein acceptors. The protein glycosylating activity remained practically the same after stripping the vesicles from their robosomes or partially releasing their vesicular content. Isolation of polysomes from rough microsomes after glycosylation has taken place, reveals that a large proportion of mannose labeled glycoproteins is in the membranous fraction. The remaining labeled glycoproteins co-sediment with the polysomal fraction. If the isolation is carried out before glycosylation only the membranous fraction shows enzyme activity, whereas the polysomes alone are not able to carry out glycosylation. All these results taken together indicate that the protein glycosylating enzyme is a structural component of the rough and smooth microsomes of rat liver.
Mol Cell Biochem 1979 Jul 31
PMID:Oligosaccharide transfer from lipid sugar intermediates to endogenous protein(s) of rat liver microsomal subfractions. 50 56

1. To evaluate potential alterations in hepatic metabolism of drugs occurring in patients with renal insufficiency the fate of aminopyrine was studied in 17 patients with chronic renal failure and in 27 normal subjects. 2. Although patients with chronic renal failure exhibited large variations, their aminopyrine plasma disappearance times (mean 0.62 +/- SD 0.24 h-1) were significantly higher than those found in normal subjects (0.30 +/- 0.07 h-1, P less than 0.002). 3. 14CO2 derived from [dimethylamine-14C]aminopyrine disappeared from breath more rapidly in patients with chronic renal failure and a history of analgesic abuse (0.40 +/- 0.04 h-1) than in control subjects (0.22 +/- 0.03 h-1, P less than 0.01) and in other patients with chronic renal failure (0.24 +/- 0.04 h-1). 4. Dialysis treatment and serum creatinine concentrations were not correlated with the rates of aminopyrine metabolism. Two additional patients, however, with combined renal and hepatic disease, exhibited markedly slowed rates of aminopyrine demethylation. 5. Although chronic renal failure by itself might not alter microsomal drug metabolism it is concluded that, in patients with a history of abuse of phenacetin-containing analgesics, marked acceleration in aminopyrine N-demethylation may be observed.
Clin Sci Mol Med 1978 Feb
PMID:Hepatic metabolism of aminopyrine in patients with chronic renal failure. 62 May 2


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