Localization and capacity of the last step of mercapturic acid biosynthesis and the reabsorption and acetylation of cysteine S-conjugates in the rat kidney.
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)
Heuner
A
A
Physiologisches Institut, Universität Würzburg, Federal Republic of Germany.
Dekant
W
W
Schwegler
J S
JS
Silbernagl
S
S
D000107:Acetylation; D000111:Acetylcysteine / Q000378:metabolism*; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
C002206:S-benzylcysteine; D003545:Cysteine; D000111:Acetylcysteine