Tissue distribution of and species differences in deacetylation of N-acetyl-L-cysteine and immunohistochemical localization of acylase I in the primate kidney.
Species differences in the biotransformation of N-acetyl-L-cysteine (NAC) have been investigated to evaluate the usefulness of NAC as a constituent in parenteral nutrition solutions in place of cysteine. The activity of NAC-deacetylating enzyme (acylase) was measured in various tissues of different species (rat, rabbit, dog, monkey, and man). Acylase activity was highest in the kidney in all species studied. Enzyme activity in the liver was 10 %-22 % of that in the kidney in the rat, rabbit, monkey, and man, but almost no hepatic activity was seen in the dog. NAC-deacetylating activity was very low in other organs. The tissue distribution of acylase I was determined by Western blotting and an immunohistochemical method employing specific antibody against porcine acylase I (EC 3.5.1.14). The immunoblotting study showed a 46-kDa protein band corresponding to porcine acylase I in the kidney of all species. In liver cytosol, 46 kDa and/or 29 kDa bands were observed in the rat, rabbit, monkey, and man, but not in the dog. In the immunohistochemical study, positive staining with anti-acylase I antibody was observed clearly in the renal proximal tubules in the monkey and man. These results suggested that the kidney and liver were the main organs responsible for the biotransformation of NAC to cysteine in mammals other than the dog.
Yamauchi
Aiko
A
Department of Pharmaceutical Information Science, Graduate School of Pharmacy, The University of Tokushima, Japan. aiko@ph2.tokushima-u.ac.jp
Ueda
Nobuhiko
N
Hanafusa
Sayuri
S
Yamashita
Eri
E
Kihara
Masaru
M
Naito
Shinsaku
S
D000107:Acetylation; D000111:Acetylcysteine / Q000493:pharmacokinetics*; D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology; D008252:Macaca fascicularis; D009928:Organ Specificity; D010288:Parenteral Nutrition; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D014018:Tissue Distribution
D000581:Amidohydrolases; C019672:aminoacylase I; D000111:Acetylcysteine