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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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
JournalAmerican Journal of Physiology - Renal Physiology
Volume306
Issue number12
DOIs
Publication statusPublished - 2014 Jun 15

Fingerprint

Cystathionine
Homocystinuria
Neutral Amino Acids
Animal Models
Kidney
Lyases
Serum
Urine
Amino Acids
Growth

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Neutral aminoaciduria in cystathionine β-synthase-deficient mice, an animal model of homocystinuria. / Akahoshi, Noriyuki; Kamata, Shotaro; Kubota, Masashi; Hishiki, Takako; Nagahata, Yoshiko; Matsuura, Tomomi; Yamazaki, Chiho; Yoshida, Yuka; Yamada, Hidenori; Ishizaki, Yasuki; Suematsu, Makoto; Kasahara, Tadashi; Ishii, Isao.

In: American Journal of Physiology - Renal Physiology, Vol. 306, No. 12, 15.06.2014.

Research output: Contribution to journalArticle

Akahoshi, N, Kamata, S, Kubota, M, Hishiki, T, Nagahata, Y, Matsuura, T, Yamazaki, C, Yoshida, Y, Yamada, H, Ishizaki, Y, Suematsu, M, Kasahara, T & Ishii, I 2014, 'Neutral aminoaciduria in cystathionine β-synthase-deficient mice, an animal model of homocystinuria', American Journal of Physiology - Renal Physiology, vol. 306, no. 12. https://doi.org/10.1152/ajprenal.00623.2013
Akahoshi, Noriyuki ; Kamata, Shotaro ; Kubota, Masashi ; Hishiki, Takako ; Nagahata, Yoshiko ; Matsuura, Tomomi ; Yamazaki, Chiho ; Yoshida, Yuka ; Yamada, Hidenori ; Ishizaki, Yasuki ; Suematsu, Makoto ; Kasahara, Tadashi ; Ishii, Isao. / Neutral aminoaciduria in cystathionine β-synthase-deficient mice, an animal model of homocystinuria. In: American Journal of Physiology - Renal Physiology. 2014 ; Vol. 306, No. 12.
@article{c8a5788c730e47c6ac29186fdb159507,
title = "Neutral aminoaciduria in cystathionine β-synthase-deficient mice, an animal model of homocystinuria",
abstract = "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.",
keywords = "Amino acid reabsorption, Amino acid transporter, Cystathionine γ-lyase, Homocystinuria, Transsulfuration",
author = "Noriyuki Akahoshi and Shotaro Kamata and Masashi Kubota and Takako Hishiki and Yoshiko Nagahata and Tomomi Matsuura and Chiho Yamazaki and Yuka Yoshida and Hidenori Yamada and Yasuki Ishizaki and Makoto Suematsu and Tadashi Kasahara and Isao Ishii",
year = "2014",
month = "6",
day = "15",
doi = "10.1152/ajprenal.00623.2013",
language = "English",
volume = "306",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "12",

}

TY - JOUR

T1 - Neutral aminoaciduria in cystathionine β-synthase-deficient mice, an animal model of homocystinuria

AU - Akahoshi, Noriyuki

AU - Kamata, Shotaro

AU - Kubota, Masashi

AU - Hishiki, Takako

AU - Nagahata, Yoshiko

AU - Matsuura, Tomomi

AU - Yamazaki, Chiho

AU - Yoshida, Yuka

AU - Yamada, Hidenori

AU - Ishizaki, Yasuki

AU - Suematsu, Makoto

AU - Kasahara, Tadashi

AU - Ishii, Isao

PY - 2014/6/15

Y1 - 2014/6/15

N2 - 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.

AB - 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.

KW - Amino acid reabsorption

KW - Amino acid transporter

KW - Cystathionine γ-lyase

KW - Homocystinuria

KW - Transsulfuration

UR - http://www.scopus.com/inward/record.url?scp=84902670111&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902670111&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.00623.2013

DO - 10.1152/ajprenal.00623.2013

M3 - Article

C2 - 24761004

AN - SCOPUS:84902670111

VL - 306

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 12

ER -