d-Serine is reabsorbed in rat renal pars recta

Abstract

d-Serine normally contributes up to 3% to total plasma serine and up to 23% in chronic renal failure. d-Serine is metabolized by tubular d-amino acid oxidase (D-AAO), and highd-serine plasma levels are nephrotoxic; both events are localized in the straight part of the proximal tubule. We therefore investigated if and howd-serine is reabsorbed there. We microinfused14C-labeledd- or -l-serine + [3H]inulin into early proximal (EP), late proximal (LP), or early distal (ED) tubule sections of superficial nephrons and into long loops of Henle (LLH) of rats in vivo and in situ. The fractional reabsorption (FR) of the14C label was determined from the14C:3H ratio in the final urine. At 0.36 mM, FR ofd-[14C]serine was 86% (EP), 90% (LP), and ≈0 (ED, LLH). FR ofd-serine could be saturated and inhibited by l-serine (and vice versa). d-methionine, but notd-glutamate ord-arginine, blocked FR ofd-serine (LP). We conlude that filtered d-serine is able to enter the pars recta cells, thereby getting access to D-AAO. The uptake carrier has a very low stereospecificity and is, therefore, different from that in the proximal convolution. The colocalization of exclusive reabsorption and metabolism makes the pars recta the tubule site for the recycling of the carbon structure of d-amino acids and, at the same time, the target ofd-serine nephrotoxicity.