Metabolic Coordination of Liver and Kidney in Mercapturic Acid Biosynthesis In Vivo

✍ Scribed by Masayasu Inoue; Kenji Okajima; Yoshimasa Morino

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 697 KB
• Volume: 2
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840020304

✦ Synopsis

When S-carbamido(14C)methy1 glutathione, a model compound of glutathione S-conjugate, was administered i.v. to mice, radioactivity accumulated in the kidney within 1 to 2 min and then decreased gradually during the following 10 to 16 min with concomitant increase in hepatic radioactivity. Most hepatic radioactivity was accounted for by S-carbamidomethyl cysteine and its N-acetyl derivative, a mercapturic acid. The i.v. administration of S-carbamido('*C)rnethyl cysteine resulted in rapid and predominant accumulation of radioactivity in the liver. In both cases, the radioactive urinary metabolites were fully accounted for by N-acetyl-S-carbamidomethyl cysteine. N-Acetyl-S-carbamid~(*~C)methyl cysteine administered to mice was accumulated preferentially in the kidney and was excreted into urine very rapidly. These results suggest the following series of events: glutathione S-conjugate accumulated mainly in the kidney and is hydrolyzed into its component amino acids, presumably by y-glutamyl transferase and some peptidase(s) on the renal brush border membranes. The cysteine S-conjugate which is formed in the tubular lumen is reabsorbed and transferred to the liver, acetylated to form N-acetylcysteine S-conjugate, and excreted in the urine. Thus, renal hydrolysis of glutathione S-conjugates seems to be coordinated with acetylation in liver and with mercapturic acid biosynthesis in vivo.