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)

Using male Fischer 344 rats classified as young (2-4 months), middle aged (12-14 months), and old (22-25 months), the activities of several Phase I and Phase II biotransformation pathways in the large intestine were investigated, including benzo[a]pyrene hydroxylase (BPOH), alcohol dehydrogenase (ADH), glutathione S-transferase (GST), glutathione peroxidase (GSH-PX), beta-glucuronidase (BG), and microsomal and nuclear glucuronyltransferase (UDPGT). Levels of oxidized (GSSG) and reduced (GSH) glutathione and uridine 5'-diphosphoglucuronic acid (UDPGA) were also measured. BPOH increased 33% in old rats, while ADH and BG activity remained unchanged with age. Nuclear UDPGT remained unchanged with age, whereas form I of GSH-PX declined slightly in old rats. GST, microsomal UDPGT, and form II of GSH-PX declined by 38, 37 and 44%, respectively, in old rats. The decrease in GST and microsomal UDPGT was also significant in middle aged rats. Levels of colonic GSH, GSSG and UDPGA were found to be unchanged with age. These in vitro data suggest the possibility that if reactive intermediates are generated to the same extent in old rats as in young rats, decreased detoxification mechanisms in the old rat may increase susceptibility of the colon to actions of chemical carcinogens.
 ...
PMID:Changes in phase I and phase II biotransformation with age in male Fischer 344 rat colon: relationship to colon carcinogenesis. 311 59

Renal cytochrome P-450 levels, metabolism of acetaminophen (APAP) and aminopyrine, and activities of several phase II-associated enzymes [UDPGT, beta-glucuronidase, and glutathione-S-transferase (GST)] were determined in sedentary and exercised young and middle-aged Fischer-344 male rats. After an 8-week exercise regimen consisting of treadmill running at a moderate intensity, renal microsomal cytochrome P-450 levels were increased 60% and 37% in young and middle-aged runners, respectively. Exercise was found to increase renal deacetylation of APAP to the nephrotoxic metabolite p-aminophenol by 54% in young and 26% in middle-aged rats. Aminopyrine N-demethylase activity was increased 97% in the young runners only. In contrast, UDPGT, beta-glucuronidase, and GST activities were unchanged by treadmill running. NADPH-cytochrome c reductase activity, determined in young animals only, was also unaltered by exercise. Advanced age decreased renal cortical cytochrome P-450 content by 34% while having no effect on p-aminophenol production. Aminopyrine N-demethylase activity was increased by 130% with increased age. The only phase II-associated enzyme altered by age was GST activity, as sedentary middle-aged animals exhibited a 43% decrease in activity when compared with young rats. Young exercised rats did not gain weight as rapidly as sedentary rats, and middle-aged rats had a slight loss in weight during exercise. Moreover, running resulted in 30-36% less food consumption during the experimental period. In conclusion, this study demonstrated that exercise increased renal phase I drug metabolism without influencing phase II processes; furthermore, a substrate-specific modification of the response to exercise was observed in the aged rats.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Increased renal drug metabolism in treadmill-exercised Fischer-344 male rats. 810 May 4