Chemical synthesis of N-acetylcysteine conjugates of bile acids and in vivo formation in cholestatic rats as shown by liquid chromatography/electrospray ionization-linear ion trap mass spectrometry.
N-Acetylcysteine (NAC) conjugates of the five major bile acids occurring in man were synthesized in order to investigate the possible formation in vivo of these conjugates. Upon collision-induced dissociation, structurally informative daughter ions were observed. The transformation of cholyl-adenylate and cholyl-CoA thioester into a N-acetyl-S-(cholyl)cysteine by rat hepatic glutathione S-transferase was confirmed by liquid chromatography/electrospray ionization-linear ion trap mass spectrometry (LC/ESI-MS(2)). Lithocholic acid was administered orally to bile duct-ligated rats that also received NAC intraperitoneally. The NAC conjugate of lithocholic acid was identified in urine by means of LC/ESI-MS(2). Rapid hydrolysis of the BA-NAC conjugates by rabbit liver carboxylesterase was found, demonstrating the possible labile nature of the NAC conjugates formed in the liver.
Mitamura
Kuniko
K
Faculty of Pharmaceutical Sciences, Kinki University, Higashi-osaka 577-8502, Japan.
Watanabe
Saai
S
Sakai
Toshihiro
T
Okihara
Rika
R
Sogabe
Mitsuru
M
Wakamiya
Tateaki
T
Hofmann
Alan F
AF
Ikegawa
Shigeo
S
D000111:Acetylcysteine / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001647:Bile Acids and Salts / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D043182:Carboxylesterase / Q000378:metabolism; D002779:Cholestasis / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D011817:Rabbits; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D001647:Bile Acids and Salts; D043182:Carboxylesterase; D000111:Acetylcysteine