title: In vivo role of aldehyde reductase.
abstract: BACKGROUND
  Aldehyde reductase (AKR1A; EC 1.1.1.2) catalyzes the reduction of various types of aldehydes. To ascertain the physiological role of AKR1A, we examined AKR1A knockout mice.
  
  
  METHODS
  Ascorbic acid concentrations in AKR1A knockout mice tissues were examined, and the effects of human AKR1A transgene were analyzed. We purified AKR1A and studied the activities of glucuronate reductase and glucuronolactone reductase, which are involved in ascorbic acid biosynthesis. Metabolomic analysis and DNA microarray analysis were performed for a comprehensive study of AKR1A knockout mice.
  
  
  RESULTS
  The levels of ascorbic acid in tissues of AKR1A knockout mice were significantly decreased which were completely restored by human AKR1A transgene. The activities of glucuronate reductase and glucuronolactone reductase, which are involved in ascorbic acid biosynthesis, were suppressed in AKR1A knockout mice. The accumulation of d-glucuronic acid and saccharate in knockout mice tissue and the expression of acute-phase proteins such as serum amyloid A2 are significantly increased in knockout mice liver.
  
  
  CONCLUSIONS
  AKR1A plays a predominant role in the reduction of both d-glucuronic acid and d-glucurono-γ-lactone in vivo. The knockout of AKR1A in mice results in accumulation of d-glucuronic acid and saccharate as well as a deficiency of ascorbic acid, and also leads to upregulation of acute phase proteins.
  
  
  CONCLUSIONS
  AKR1A is a major enzyme that catalyzes the reduction of d-glucuronic acid and d-glucurono-γ-lactone in vivo, besides acting as an aldehyde-detoxification enzyme. Suppression of AKR1A by inhibitors, which are used to prevent diabetic complications, may lead to the accumulation of d-glucuronic acid and saccharate.
authors: Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo, Japan. takam@sapmed.ac.jp
authors: Motoko
authors: M
authors: Takahashi
authors: Satoshi
authors: S
authors: Miyata
authors: Junichi
authors: J
authors: Fujii
authors: Yoko
authors: Y
authors: Inai
authors: Shigemitsu
authors: S
authors: Ueyama
authors: Motoko
authors: M
authors: Araki
authors: Tomoyoshi
authors: T
authors: Soga
authors: Reiko
authors: R
authors: Fujinawa
authors: Chiaki
authors: C
authors: Nishitani
authors: Shigeru
authors: S
authors: Ariki
authors: Takeyuki
authors: T
authors: Shimizu
authors: Tomomi
authors: T
authors: Abe
authors: Yoshito
authors: Y
authors: Ihara
authors: Morimitsu
authors: M
authors: Nishikimi
authors: Yasunori
authors: Y
authors: Kozutsumi
authors: Naoyuki
authors: N
authors: Taniguchi
authors: Yoshio
authors: Y
authors: Kuroki
mesh_terms: D000449:Aldehyde Reductase / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001205:Ascorbic Acid / Q000032:analysis; D002135:Calcium-Binding Proteins / Q000032:analysis; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D020723:Glucuronic Acid / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis; D008099:Liver / Q000737:chemistry; D008297:Male; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D002135:Calcium-Binding Proteins; D005965:Glucuronates; D047908:Intracellular Signaling Peptides and Proteins; C513324:Rgn protein, mouse; C004940:glucuronolactone; D020723:Glucuronic Acid; D000449:Aldehyde Reductase; D001205:Ascorbic Acid