PMID- 3606632
OWN - NLM
STAT- MEDLINE
DCOM- 19870803
LR  - 20190623
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 36
IP  - 13
DP  - 1987 Jul 1
TI  - Inter-organ metabolism and transport of a cysteine-S-conjugate of xenobiotics in 
      normal and mutant analbuminemic rats.
PG  - 2145-50
AB  - Biosynthesis of N-acetylcysteine S-conjugates of toxic electrophiles, mercapturic 
      acids, occurs via inter-organ metabolism and transport in which liver, small 
      intestine and kidney play an important role. Since a mercapturic acid is a 
      hydrophobic organic anion and strongly binds to plasma albumin in vitro, the 
      ligand-albumin interaction may affect the metabolic fate of this final metabolite 
      in vivo. To investigate the role of the circulating albumin in detoxication and 
      elimination of a toxic electrophile, urinary occurrence of the final metabolite 
      was determined in normal and mutant Nagase analbuminemic rats (NAR) after 
      administration of S-benzylcysteine, a model compound of cysteine conjugates. 
      S-Benzylcysteine intravenously administered was excreted rapidly into urine as 
      its N-acetyl derivative in both animal groups. However, the urinary recovery of 
      this mercapturic acid was significantly lower in NAR than in normal animals. The 
      lower urinary recovery in NAR was due to a rapid and random distribution of the 
      unbound metabolite in the circulation to extrarenal tissues. In contrast, no 
      significant difference in the urinary recovery of the final metabolite was 
      observed between the two animal groups if S-benzylcysteine was given orally. 
      Kinetic analysis revealed that the major part of the orally administered 
      S-benzylcysteine was transferred to the liver and acetylated predominantly in 
      this organ in both animal groups; the mercapturic acid which was synthesized in 
      the liver can be transferred to the kidney and excreted into urine even in the 
      absence of the circulating albumin. These results indicate that albumin is 
      important for a final elimination of a mercapturic acid when animals were 
      extraorally challenged with a large dose of toxic electrophiles by which the rate 
      of biosynthesis and the plasma level of the amphipathic metabolites were 
      increased.
FAU - Inoue, M
AU  - Inoue M
FAU - Okajima, K
AU  - Okajima K
FAU - Nagase, S
AU  - Nagase S
FAU - Morino, Y
AU  - Morino Y
LA  - eng
PT  - Journal Article
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Blood Proteins)
RN  - 0 (Serum Albumin)
RN  - 9VRE13M548 (S-benzylcysteine)
RN  - EC 2.3.1.5 (Arylamine N-Acetyltransferase)
RN  - K848JZ4886 (Cysteine)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylation
MH  - Acetylcysteine/*metabolism
MH  - Animals
MH  - Arylamine N-Acetyltransferase/metabolism
MH  - Blood Proteins/metabolism
MH  - Cysteine/*analogs & derivatives/urine
MH  - Intestine, Small/enzymology
MH  - Kidney/enzymology
MH  - Kinetics
MH  - Liver/enzymology
MH  - Male
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Serum Albumin/*deficiency/physiology
EDAT- 1987/07/01 00:00
MHDA- 1987/07/01 00:01
CRDT- 1987/07/01 00:00
PHST- 1987/07/01 00:00 [pubmed]
PHST- 1987/07/01 00:01 [medline]
PHST- 1987/07/01 00:00 [entrez]
AID - 0006-2952(87)90143-2 [pii]
AID - 10.1016/0006-2952(87)90143-2 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1987 Jul 1;36(13):2145-50. doi: 10.1016/0006-2952(87)90143-2.