The hypotaurine-taurine pathway as an antioxidative mechanism in patients with acute liver failure

Takamasa Mizota, Takako Hishiki, Masahiro Shinoda, Yoshiko Naito, Kazuya Hirukawa, Yohei Masugi, Osamu Itano, Hideaki Obara, Minoru Kitago, Hiroshi Yagi, Yuta Abe, Kentaro Matsubara, Makoto Suematsu, Yuko Kitagawa

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The liver has been thought to protect against oxidative stress through mechanisms involving reduced glutathione (GSH) that consumes high-energy phosphor-nucleotides on its synthesis. However, hepatoprotective mechanisms in acute liver failure (ALF) where the phosphor-nucleotides are decreased in remain to be solved. Liver tissues were collected from patients with ALF and liver cirrhosis (LC) and living donors (HD) who had undergone liver transplantation. Tissues were used for metabolomic analyses to determine metabolites belonging to the central carbon metabolism, and to determine sulfur-containing metabolites. ALF and LC exhibited a significant decline in metabolites of glycolysis and pentose phosphate pathways and high-energy phosphor-nucleotides such as adenosine triphosphate as compared with HD. Conversely, methionine, S-adenosyl-L-methionine, and the ratio of serine to 3-phosphoglycerate were elevated significantly in ALF as compared with LC and HD, suggesting a metabolic boost from glycolysis towards trans-sulfuration. Notably in ALF, the increases in hypotaurine (HTU) + taurine (TU) coincided with decreases in the total amounts of reduced and oxidized glutathione (GSH + 2GSSG). Plasma NH3 levels correlated with the ratio of HTU + TU to GSH + 2GSSG. Increased tissue levels of HTU + TU vs total glutathione appear to serve as a biomarker correlating with hyperammonemia, suggesting putative roles of the HTU-TU pathway in anti-oxidative protective mechanisms.

Original languageEnglish
Pages (from-to)54-63
Number of pages10
JournalJournal of Clinical Biochemistry and Nutrition
Volume70
Issue number1
DOIs
Publication statusPublished - 2021

Keywords

  • Acute liver failure
  • Glutathione
  • Hyperammonemia
  • Hypotaurine
  • Metabolome analysis

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Clinical Biochemistry

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