Postnatal changes in hepatic microsomal enzyme activities in the puppy.
The in vitro activities of glucose-6-phosphatase (G6P), UDP-glucuronyl transferase (GT) and P-450 were measured in liver homogenate and/or microsomal suspensions from puppies, 0-42 days of age (n = 26), and adult dogs (n = 3). For each of these enzymes, an age-related increase in the in vitro activity was observed, with the lowest value detected at birth. By the 28th-42nd day of postnatal life, P-450-specific activity was 350 and 85%, G6P 225 and 188%, p-nitrophenol GT 430 and 105% and bilirubin GT 317 and 123% of that seen in 0-hour-old puppies and adults dogs, respectively. The age-related changes in G6P and GT were observed when native enzymes or enzymes activated by deoxycholate or UDP-N-acetylglucosamine (GT) were used. However, the ratio between activated and native p-nitrophenol GT activity decreased as a function of age, and UDP-N-acetylglucosamine failed to activate bilirubin GT in puppies of 0-42 days of age. Total liver protein also increased with age, and hepatic water content was significantly higher in 0- to 42-day-old puppies (76.3%) than in adult dogs (71.4%). Thus, differences between puppies and adult animals were not the same when protein content or enzyme activities were expressed per unit of wet or dried liver weight. Phenobarbital, injected intraperitoneally at 15 mg/kg/day for 6 consecutive days to 8- to 13-day-old puppies (n = 3), produced induction of P-450 (235% of age-matched controls) and bilirubin GT activity (160%), diminished G6P activity (81%), and failed to modify p-nitrophenol GT activity (102%). These studies indicate that, in the puppy, (1) the in vitro activities of P-450, G6P and GT are immature at birth and develop during postnatal life; (2) as in other species, bilirubin and p-nitrophenol may be conjugated in the dog liver by two functionally distinct GT.
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D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001835:Body Weight; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004285:Dogs; D005260:Female; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009929:Organ Size; D010634:Phenobarbital / Q000494:pharmacology
D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D005952:Glucose-6-Phosphatase; D010634:Phenobarbital