Neutral aminoaciduria in cystathionine β-synthase-deficient mice, an animal model of homocystinuria

Noriyuki Akahoshi, Shotaro Kamata, Masashi Kubota, Takako Hishiki, Yoshiko Nagahata, Tomomi Matsuura, Chiho Yamazaki, Yuka Yoshida, Hidenori Yamada, Yasuki Ishizaki, Makoto Suematsu, Tadashi Kasahara, Isao Ishii

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13 Citations (Scopus)


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 wk, 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-wk-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.

Original languageEnglish
Pages (from-to)F1462-F1476
JournalAmerican Journal of Physiology - Renal Physiology
Issue number12
Publication statusPublished - 2014 Jun 15


  • Amino acid reabsorption
  • Amino acid transporter
  • Cystathionine γ-lyase
  • Homocystinuria
  • Transsulfuration

ASJC Scopus subject areas

  • Physiology
  • Urology


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