Localization and capacity of the last step of mercapturic acid biosynthesis and the reabsorption and acetylation of cysteine S-conjugates in the rat kidney
- PMID: 2011474
- DOI: 10.1007/BF00370949
Localization and capacity of the last step of mercapturic acid biosynthesis and the reabsorption and acetylation of cysteine S-conjugates in the rat kidney
Abstract
We investigated the capacity and the localization of N-acetylation of the mercapturic acid precursor S-benzyl-L-cysteine (BC), as well as the tubular reabsorption of this compound in the rat kidney in vivo et situ by renal clearance and continuous microinfusion and microperfusion experiments. In renal clearance experiments. 450 mumol BC was infused intravenously for 180 min. During the time of BC infusion and the following 180 min, the two kidneys excreted 400 mumol or 90% of the infused BC dose as the mercapturate N-acetyl-S-benzyl-L-cysteine (AcBC). Comparison of the amounts of BC and AcBC entering the left kidney via the renal artery with those leaving it via the renal vein and the ureter showed that 0.13 +/- 0.04 mumol BC/min (mean +/- SEM) was extracted and 0.24 +/- 0.08 mumol AcBC/min was formed by one kidney. The intrarenal acetylation can account for the formation of 38% of the mercapturate excreted in the final urine. In additional experiments, 50 pmol/min [14C]BC was microinfused into single superficial tubules at three different sites. During microinfusion into early proximal tubules, the final urine contained 16.3 +/- 1.8% of the microinfused radioactivity as AcBC, but no BC. When [14C]BC was microinfused into late proximal tubules, 13.0 +/- 2.3% of the infused label was recovered as BC, 28.1 +/- 2.3% as AcBC. During microinfusion into early distal tubules, the final urine contained no AcBC, but 90.3 +/- 2.1% of the infused [14C]BC was recovered.(ABSTRACT TRUNCATED AT 250 WORDS)
Similar articles
-
Hepato-renal cooperation in biotransformation, membrane transport, and elimination of cysteine S-conjugates of xenobiotics.J Biochem. 1984 Jan;95(1):247-54. doi: 10.1093/oxfordjournals.jbchem.a134591. J Biochem. 1984. PMID: 6706912
-
Metabolism of L-cysteine S-conjugates and N-(trideuteroacetyl)-L-cysteine S-conjugates of four fluoroethylenes in the rat. Role of balance of deacetylation and acetylation in relation to the nephrotoxicity of mercapturic acids.Biochem Pharmacol. 1991 Jun 21;42(1):31-8. doi: 10.1016/0006-2952(91)90677-w. Biochem Pharmacol. 1991. PMID: 2069595
-
Metabolic coordination of liver and kidney in mercapturic acid biosynthesis in vivo.Hepatology. 1982 May-Jun;2(3):311-6. doi: 10.1002/hep.1840020304. Hepatology. 1982. PMID: 7076112
-
Glutathione conjugation and conversion to mercapturic acids can occur as an intrahepatic process.J Toxicol Environ Health. 1994 Apr;41(4):387-409. doi: 10.1080/15287399409531852. J Toxicol Environ Health. 1994. PMID: 8145281 Review.
-
Mercapturate Pathway in the Tubulocentric Perspective of Diabetic Kidney Disease.Nephron. 2019;143(1):17-23. doi: 10.1159/000494390. Epub 2019 Jan 9. Nephron. 2019. PMID: 30625494 Review.
Cited by
-
On leaking into the lumen, amino acids cross the tubule cells. Secretion of L-citrulline in the isolated-perfused non-filtering kidney of the African clawed toad (Xenopus laevis).Pflugers Arch. 1991 Nov;419(5):499-503. doi: 10.1007/BF00370795. Pflugers Arch. 1991. PMID: 1775372
-
Simultaneous detection of the tetrachloroethylene metabolites S-(1,2,2-trichlorovinyl) glutathione, S-(1,2,2-trichlorovinyl)-L-cysteine, and N-acetyl-S-(1,2,2-trichlorovinyl)-L-cysteine in multiple mouse tissues via ultra-high performance liquid chromatography electrospray ionization tandem mass spectrometry.J Toxicol Environ Health A. 2017;80(9):513-524. doi: 10.1080/15287394.2017.1330585. Epub 2017 Jul 11. J Toxicol Environ Health A. 2017. PMID: 28696834 Free PMC article.
-
Developing urinary pyrrole-amino acid adducts as non-invasive biomarkers for identifying pyrrolizidine alkaloids-induced liver injury in human.Arch Toxicol. 2021 Oct;95(10):3191-3204. doi: 10.1007/s00204-021-03129-6. Epub 2021 Aug 14. Arch Toxicol. 2021. PMID: 34390356 Free PMC article.