The kidney is one of the major loci for the expression of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH). While CBS-deficient (Cbs-/-) mice display homocysteinemia/methioninemia and severe growth retardation, and rarely survive beyond the first 4 weeks, CTH-deficient (Cth-/-) mice show homocysteinemia/cystathioninemia but develop with no apparent abnormality. This study examined renal amino acid reabsorption in those mice. Although both 2-week-old Cbs-/- and Cth-/- mice had normal renal architecture, their serum/urinary amino acid profiles largely differed from wild-type mice. The most striking feature was marked accumulation of Met and cystathionine in serum/urine/kidney samples of Cbs-/- and Cth-/- mice, respectively. Levels of some neutral amino acids (Val, Leu, Ile, and Tyr) that were not elevated in Cbs-/- serum were highly elevated in Cbs-/- urine, and urinary excretion of other neutral amino acids (except Met) was much higher than expected from their serum levels, demonstrating neutral aminoaciduria in Cbs-/- (not Cth-/-) mice. Because the bulk of neutral amino acids is absorbed via a B0AT1 transporter and Met has the highest substrate affinity for B0AT1 than other neutral amino acids, hypermethioninemia may cause hyperexcretion of neutral amino acids.
- amino acid reabsorption
- amino acid transport
- cystathionine gamma-lyase
- Copyright © 2013, American Journal of Physiology - Renal Physiology