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)

Mitiglinide (MGN) is a new potassium channel antagonist for the treatment of type 2 diabetes mellitus. In the present study, a potential metabolic pathway of MGN, via carboxyl-linked glucuronic acid conjugation, was found. MGN carboxyl-glucuronide was isolated from a reaction mixture consisting of MGN and human liver microsomes fortified with UDP-glucuronic acid (UDPGA) and identified by a hydrolysis reaction with beta-glucuronidase and HPLC-MS/MS. Kinetic analysis indicated that MGN from four species had the highest affinity for the rabbit liver microsomal enzyme (K(m)=0.202 mM) and the lowest affinity for the dog liver microsomal enzyme (K(m)=1.164 mM). The metabolic activity (V(max)/K(m)) of MGN to the carboxyl-glucuronidation was in the following order: rabbit>dog>rat>human. With the assessment of MGN glucuronide formation across a panel of recombinant UDP-glucuronosyltransferase (UGT) isoforms (UGT1A3, UGT1A4, UGT1A6, UGT1A9, and UGT2B7), only UGT1A3 and UGT2B7 exhibited high MGN glucuronosyltransferase activity. The K(m) values of MGN glucuronidation in recombinant UGT1A3 and UGT2B7 microsomes were close to those in human liver microsomes. The formation of MGN glucuronidation by human liver microsomes was effectively inhibited by quercetin (substrate for UGT1A3) and diclofenac (substrate for UGT2B7), respectively. The MGN glucuronidation activities in 15 human liver microsomes were significantly correlated with quercetin (r(2)=0.806) and diclofenac glucuronidation activities (r(2)=0.704), respectively. These results demonstrate that UGT1A3 and UGT2B7 are catalytic enzymes in MGN carboxyl-glucuronidation in human liver.
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PMID:Carboxyl-glucuronidation of mitiglinide by human UDP-glucuronosyltransferases. 1735 41

Little is known about the molecular and regulatory mechanisms of long-distance nitrate transport in higher plants. NRT1.5 is one of the 53 Arabidopsis thaliana nitrate transporter NRT1 (Peptide Transporter PTR) genes, of which two members, NRT1.1 (CHL1 for Chlorate resistant 1) and NRT1.2, have been shown to be involved in nitrate uptake. Functional analysis of cRNA-injected Xenopus laevis oocytes showed that NRT1.5 is a low-affinity, pH-dependent bidirectional nitrate transporter. Subcellular localization in plant protoplasts and in planta promoter-beta-glucuronidase analysis, as well as in situ hybridization, showed that NRT1.5 is located in the plasma membrane and is expressed in root pericycle cells close to the xylem. Knockdown or knockout mutations of NRT1.5 reduced the amount of nitrate transported from the root to the shoot, suggesting that NRT1.5 participates in root xylem loading of nitrate. However, root-to-shoot nitrate transport was not completely eliminated in the NRT1.5 knockout mutant, and reduction of NRT1.5 in the nrt1.1 background did not affect root-to-shoot nitrate transport. These data suggest that, in addition to that involving NRT1.5, another mechanism is responsible for xylem loading of nitrate. Further analyses of the nrt1.5 mutants revealed a regulatory loop between nitrate and potassium at the xylem transport step.
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PMID:Mutation of the Arabidopsis NRT1.5 nitrate transporter causes defective root-to-shoot nitrate transport. 1878 Aug 2

Altered membrane integrity has been suggested as a major factor in the development of cellular injury during myocardial necrosis. The present study was designed to investigate the effect of diosgenin on lysosomal hydrolases, membrane-bound enzymes, and electrolytes during isoproterenol (ISO)-induced myocardial necrosis in rats. Animals were pretreated with DIOS (80 mg/kg) for a period of 35 days. Myocardial infarction was experimentally induced with ISO (85 mg/kg) twice at 24 h interval. Experimental myocardial infarction was evidenced with marked elevation of creatine kinase-MB (CK-MB) in serum with concomitant increase in lipid peroxidation (plasma thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HP)). Activity of lysosomal hydrolases (beta-glucuronidase, beta-N-acetyl glucosaminidase, beta-D-galactosidase, cathepsin D, and acid phosphatase) was found to be increased in serum and heart tissue of ISO-alone treated animals. DIOS (80 mg/kg) pretreated groups showed significant decrease in CK-MB, lipid peroxidation, and lysosomal hydrolases activity. The membrane-bound enzymes such as Ca2+-ATPase and Mg2+-ATPase activity was increased and Na+/K+-ATPase activity was decreased in the heart tissues of ISO-alone treated animals. These enzyme alterations lead to the change in the electrolytes content such as sodium, potassium, and calcium in the heart tissue. However, DIOS (80 mg/kg) pretreatment reversed the membrane-bound enzymes activity and thereby maintained the normal electrolyte concentration. These results suggest the protective action of diosgenin in ISO-induced myocardial infarction. The salubrious effect observed in this study might be due to the antioxidant and membrane stabilizing potential of diosgenin.
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PMID:Antilipoperoxidative and membrane stabilizing effect of diosgenin, in experimentally induced myocardial infarction. 1923 76


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