Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whereas the phosphorolytic breakdown of liver glycogen is known to be of great physiological importance, the functional role of the hydrolytic glycogenolysis in the lysosomal system is less well understood. In the present study the effects of fasting, alpha- and beta-adrenoceptor antagonism and insulin-induced hypoglycaemia on liver lysosomal glycogen-hydrolysing enzyme activity were investigated in mice. In freely fed mice the glycogen-hydrolysing activity (acid amyloglucosidase) was only 50% of the maltose-hydrolysing activity (acid maltase). Starvation for 24 h reduced the acid amyloglucosidase activity by approximately 30% (P less than 0.001), whereas the activities of acid maltase, acid phosphatase and beta-glucuronidase appeared unaffected. N-acetyl-beta-D-glucosaminidase activity was moderately (20%; P less than 0.01) enhanced by fasting. Thus, liver lysosomal enzyme activities may change independently of each other during fasting. Further, during short-term hypoglycaemic conditions (45 min) induced by endogenous or exogenous insulin, the activity of liver acid amyloglucosidase was found to be moderately reduced (15-20%). Blockade of alpha- and beta-adrenoceptors by phentolamine and propranolol did not result in any apparent influence on acid amyloglucosidase activity except for the indirect effect exerted by the phentolamine-induced hypoglycaemia. A moderate negative correlation (r = -0.51; P less than 0.001) between total liver glycogen concentration and acid amyloglucosidase activity was observed in a series of 43 freely fed NMRI mice. Our data show that in mouse liver the acid maltase activity predominates over the acid amyloglucosidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Glycogen and glycogen-hydrolysing lysosomal enzyme activity in mouse liver: effects of fasting, adrenoceptor antagonism and insulin-induced hypoglycaemia. 289 Feb 62

Previous studies have suggested that increased alpha adrenergic activity stimulated prostaglandin synthesis and may be involved in the modulation of eicosanoid metabolism. These observations prompted investigation of the effect of the alpha adrenergic receptor antagonist phenoxybenzamine and the cyclo-oxygenase inhibitor indomethacin on endotoxin-induced shock severity, and on plasma immunoreactive iTxB2 and i6-keto-PGF1 alpha, the stable metabolites of TxA2 and PGI2, respectively. Pretreatment with indomethacin alone blunted the endotoxin- (8 mg/kg) induced hypoglycemia. Phenoxybenzamine pretreatment also blunted endotoxin-induced mortality (LD80), hypoglycemia, hemoconcentration, and decreased plasma beta-glucuronidase (BG). The combination of phenoxybenzamine and indomethacin resulted in the improvement of all indices of shock severity. Rats pretreated with phenoxybenzamine and indomethacin alone or conjointly also exhibited significantly (P less than 0.05) enhanced survival compared to that of shocked control rats. Percent survival at 48 hr was 24, 64, 80, and 92 in untreated, indomethacin, phenoxybenzamine, and indomethacin + phenoxybenzamine treated, respectively. Mean plasma iTxB2 values at 30 min postendotoxin (15 mg/kg i.v.) were 1,532 +/- 319 pg/ml (N = 10). Phenoxybenzamine pretreatment decreased iTxB2 to 719 +/- 114 pg/ml (N = 10). Phenoxybenzamine pretreatment decreased iTxB2 to 719 +/- 114 pg/ml (N = 10) (P less than 0.05). Plasma i6-keto-PGF1 alpha was increased 4 hr after endotoxin in shocked controls to 4,161 +/- 885 pg/ml (N = 5) and attenuated by phenoxybenzamine to a value of 1,184 +/- 363 pg/ml (N = 4) (P less than 0.05). The results suggest that increased alpha adrenergic activity may be an important stimulus for arachidonic acid metabolism during endotoxemia.
 ...
PMID:The effects of alpha adrenergic blockade on arachidonic acid metabolism and shock sequelae in endotoxemia. 309 91

Streptococcal pyrogenic exotoxin (SPE) dramatically potentiates the lethal shock induced by gram-negative bacterial endotoxin. To provide further understanding of the mechanism underlying the potentiating effect, the physiological basis for the toxic synergism of the two toxins was investigated. Pretreatment of rabbits with an intravenous (i.v.) dose (10 micrograms/kg of body weight) of SPE greatly enhanced the endotoxin lethality and reduced the 50% lethal dose to less than 5 micrograms of endotoxin per kg. The SPE pretreatment dose caused severe pathophysiological changes in combination with a small i.v. dose of endotoxin (1 microgram/kg). These changes included transient hyperglycemia followed by profound hypoglycemia, elevation of the blood lipoperoxide level, and an acute increase in plasma beta-glucuronidase activity. These changes were comparable with those in animals given a large i.v. dose of endotoxin (100 micrograms/kg) alone. An injection of SPE alone did not alter any of the parameters described above. These results suggest that SPE renders rabbits more sensitive to extensive pathophysiologic effects of endotoxin, and the potentiating effect on endotoxin lethality may thus involve a general potentiation of physiologic failures. The SPE pretreatment depressed the vascular clearance of a large dose of endotoxin (100 micrograms/kg) but failed to affect that of a small dose of endotoxin (1 microgram/kg). The data suggest that the potentiating effect is not readily explained solely on the basis of the decreased clearance of endotoxin.
 ...
PMID:Physiology of the potentiation of lethal endotoxin shock by streptococcal pyrogenic exotoxin in rabbits. 330 6

Octanoyl-beta-D-glucuronide was identified in the urine of five patients with hypoketotic hypoglycemia and dicarboxylic aciduria due to a defective beta-oxidation of medium-chain fatty acids. Two subjects who ingested large amounts of medium-chain triglycerides also excreted large amounts of the glucuronide. The substance was extracted from the urine with ethyl acetate and analyzed by: (1) gas chromatography/mass spectrometry (GC-MS) of the trimethylsilyl derivative and (2) preparative one-dimensional thin-layer chromatography followed by enzymatic hydrolysis with beta-glucuronidase and again GC-MS. A quantitative analysis was performed indirectly by measuring the urinary bound octanoate after the removal of octanoylcarnitine. Octanoylglucuronide represents an additional mechanism for the detoxification of octanoate; its formation may be of help for the maintenance of carnitine homeostasis in patients with medium-chain acyl-CoA dehydrogenase deficiency.
 ...
PMID:Octanoylglucuronide excretion in patients with a defective oxidation of medium-chain fatty acids. 406 33

Endotoxic shock is associated with increased metabolism of arachidonic acid to thromboxanes (TX) and prostaglandins (PG). This study assessed the effects of varied doses of aspirin, an inhibitor of arachidonic acid metabolism, on Salmonella enteriditis endotoxin (20 mg/kg)-induced mortality, plasma levels of arachidonate metabolites and other pathophysiological sequelae in Long-Evans rats. Aspirin, in doses of 3.75, 15 an 30 mg/kg, given 30 min before endotoxin significantly (P less than .01) improved 24-hr survival from 11% to 60 to 70%, but 100 mg/kg afforded no protection. Pretreatment with aspirin (15 or 100 mg/kg) 30 min before endotoxin significantly (P less than .001) decreased the endotoxin-induced elevations in plasma levels of immunoreactive (i) TXB2, a stable metabolite of TXA2, i6-keto PGF1 alpha, a stable metabolite of PGI2 and significantly (P less than .05) inhibited thrombin-induced in vitro platelet iTXB2 synthesis. Endotoxin-induced hypoglycemia and elevations in serum acid phosphatase and beta-glucuronidase activities, lysosomal enzymes, were all significantly (P less than .01) attenuated by pretreatment with aspirin (15 mg/kg) 30 min before endotoxin. Aspirin (15 or 100 mg/kg) given 24 h before challenge with endotoxin significantly improved 24-hr survival to 42 (P less than .01) and 44% (P less than .005), respectively. Although 24 hr pretreatment with aspirin (15 or 100 mg/kg) significantly (P less than .001) reduced endotoxin-induced elevations in iTXB2, only the 100 mg/kg dose significantly lowered plasma levels of i6-keto PGF1 alpha. These observations are consistent with the notion that the beneficial effects of aspirin seen in experimental endotoxic shock may be mediated, in part, via reduction of platelet TXA2 synthesis.
 ...
PMID:Protective effects of aspirin in endotoxic shock. 689 70

The response of the pony to increasing doses of Escherichia coli endotoxin was evaluated using intravenous and intraperitoneal administration models. Marked changes were seen in all parameters measured following endotoxin administration. Leukopenia (neutropenia, lymphopenia) and thrombocytopenia were not dose-dependent. Similarly, elevated plasma fibrinogen and altered glucose concentrations (hyperglycemia and hypoglycemia), pyrexia and increased lactate/pyruvate ratios were apparent at all endotoxin doses but were not dose related. The widely used packed cell volume and capillary refill time, we well as blood lactate and possibly serum beta-glucuronidase, were increased in a dose-related manner.
 ...
PMID:Dose-response of ponies to parenteral Escherichia coli endotoxin. 702 Aug 94

Klotho gene mutation leads to a syndrome strangely resembling chronic kidney disease patients undergoing dialysis with multiple accelerated age-related disorders, including hypoactivity, sterility, skin thinning, muscle atrophy, osteoporosis, vascular calcifications, soft-tissue calcifications, defective hearing, thymus atrophy, pulmonary emphysema, ataxia, and abnormalities of the pituitary gland, as well as hypoglycemia, hyperphosphatemia, and paradoxically high-plasma calcitriol levels. Conversely, mice overexpressing klotho show an extended existence and a slow aging process through a mechanism that may involve the induction of a state of insulin and oxidant stress resistance. Two molecules are produced by the klotho gene, a membrane bound form and a circulating form. However, their precise biological roles and molecular functions have been only partly deciphered. Klotho can act as a circulating factor or hormone, which binds to a not yet identified high-affinity receptor and inhibits the intracellular insulin/insulin-like growth factor-1 (IGF-1) signaling cascade; klotho can function as a novel beta-glucuronidase, which deglycosylates steroid beta-glucuronides and the calcium channel transient receptor potential vallinoid-5 (TRPV5); as a cofactor essential for the stimulation of fibroblast growth factor (FGF) receptor by FGF23. The two last functions have propelled klotho to the group of key factors regulating mineral and vitamin D metabolism, and have also stimulated the interest of the nephrology community. The purpose of this review is to provide a nephrology-oriented overview of klotho and its potential implications in normal and altered renal function states.
 ...
PMID:Klotho: an antiaging protein involved in mineral and vitamin D metabolism. 2241 41