RGD Reference Report - In vivo role of aldehyde reductase. - Rat Genome Database

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In vivo role of aldehyde reductase.

Authors: Takahashi, Motoko  Miyata, Satoshi  Fujii, Junichi  Inai, Yoko  Ueyama, Shigemitsu  Araki, Motoko  Soga, Tomoyoshi  Fujinawa, Reiko  Nishitani, Chiaki  Ariki, Shigeru  Shimizu, Takeyuki  Abe, Tomomi  Ihara, Yoshito  Nishikimi, Morimitsu  Kozutsumi, Yasunori  Taniguchi, Naoyuki  Kuroki, Yoshio 
Citation: Takahashi M, etal., Biochim Biophys Acta. 2012 Nov;1820(11):1787-96. doi: 10.1016/j.bbagen.2012.07.003. Epub 2012 Jul 20.
RGD ID: 13825440
Pubmed: PMID:22820017   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbagen.2012.07.003   (Journal Full-text)


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.
GENERAL SIGNIFICANCE: 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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Akr1a1RatD-glucuronate catabolic process involved_inIMP PMID:22820017UniProt 
Akr1a1RatL-ascorbic acid biosynthetic process involved_inIMP PMID:22820017UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Akr1a1Ratglucuronolactone reductase activity enablesIDA PMID:22820017UniProt 
Akr1a1RatL-glucuronate reductase activity enablesIDA PMID:22820017UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Akr1a1  (aldo-keto reductase family 1 member A1)


Additional Information