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AKR7A2  -  aldo-keto reductase family 7, member A2...

Homo sapiens

Synonyms: AFAR, AFAR1, AFB1 aldehyde reductase 1, AFB1-AR 1, AFB1-AR1, ...
 
 
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Disease relevance of AKR7A2

  • Elevation of AKR7A2 (succinic semialdehyde reductase) in neurodegenerative disease [1].
  • Overall, 73 (19.7%) were HIV-1 positive, but prevalence was three times higher among the 237 women of Amhara ethnicity compared to the 112 of Afar ethnicity (24.9% vs 8.0%, p < 0.001), and almost three times higher for urban compared to rural residents (23.2% vs 8.8%, p < 0.001) [2].
  • There was a significant difference in the prevalence of brucellosis (chi2 = 7.91, p < 0.05), which was highest in Afar (5.2%) followed by Somali (2.8%) and Borena (1.2%) regions [3].
  • Mastitis in lactating camels (Camelus dromedarius) in Afar Region, north-eastern Ethiopia [4].
  • Haematobium schistosomiasis among seminomadic and agricultural Afar in Ethiopia [5].
 

High impact information on AKR7A2

  • Resolution of these problems would shed light on hominid phylogeny in general and on the ancestry of later Australopithecus and Homo. Fossils discovered in the Afar of Ethiopia in 1990 constitute the first major addition to the 3-4 million year (Myr) hominid record since the 1970s [6].
  • From this region we have now cloned a gene encoding a protein of 330 amino acids that is 78% identical with the Rattus norvegicus aflatoxin B1 aldehyde reductase (Afar) and, therefore, likely represents its human homologue [7].
  • In rat liver, Afar is strongly inducible by the antioxidants ethoxyquin and butylated hydroxyanisole, which protect the rat against aflatoxin B1-induced liver tumorigenesis by detoxifying its genotoxic and cytotoxic dialdehyde [7].
  • Fluorescent in situ hybridization localized AFAR1 to rat chromosome 5q36.5, a region that is syntenic with human chromosome 1p35-1p36.1 where AKR7A2 resides [8].
  • The 5'-flanking region of AFAR1 was isolated by polymerase chain reaction-based genome walking, and resulted in the isolation of approximately 900 bp of genomic DNA upstream from the TSS [8].
 

Chemical compound and disease context of AKR7A2

  • Reliable estimation of HIV-1 prevalence in Afar Region will require more flexible strategies that permit sampling of rural Afar residents [2].
 

Biological context of AKR7A2

 

Anatomical context of AKR7A2

 

Associations of AKR7A2 with chemical compounds

  • Aflatoxin B1 aldehyde reductases, specifically the NADPH-dependent aldo-keto reductases of rat (AKR7A1) and human (AKR7A2), are known to metabolize the AFB1 dihydrodiol by forming AFB1 dialcohol [10].
  • Comparison between the kinetic properties of AKR7A2 and AKR1A1 showed that both recombinant enzymes exhibited roughly similar k(cat)/K(m) values for SSA, 1,2-NQ and 16-ketoestrone [9].
  • In the present study, we examined the cellular expression of AKR family member, succinic semialdehyde reductase (AKR7A2) that reduces toxic aldehydes as well as catalyzing the biosynthesis of the neuromodulator gamma-hydroxybutyrate (GHB) [1].
  • Although the two AKR7 proteins are predicted to possess distinct secondary structural features which distinguish them from the prototypic AKR1 family of AKRs, the catalytic- and NADPH-binding residues appear to be conserved in both families [11].
  • Both BHA and BHT were also able to induce this enzyme but, by contrast, PB was found to be a poor inducer of AFB1-AR [12].
 

Analytical, diagnostic and therapeutic context of AKR7A2

  • Immunohistochemistry of human kidney demonstrated that AKR7A2 is expressed in a similar fashion to the AKR1 family members in proximal and distal convoluted renal tubules [9].
  • Molecular cloning, expression and catalytic activity of a human AKR7 member of the aldo-keto reductase superfamily: evidence that the major 2-carboxybenzaldehyde reductase from human liver is a homologue of rat aflatoxin B1-aldehyde reductase [11].
  • Here we report on stratigraphically associated Late Middle Pleistocene artefacts and fossils from fluvial and lake margin sandstones of the Upper Herto Member of the Bouri Formation, Middle Awash, Afar Rift, Ethiopia [13].
  • HIV-1 seroprevalence and subtypes in police recruits from Afar regional state, Ethiopia [14].
  • According to the Demographic and Health Survey (DHS) 2000, only 4.5% of the population of Afar Region is of Amhara ethnicity, and 7.8% urban residents [2].

References

  1. Elevation of AKR7A2 (succinic semialdehyde reductase) in neurodegenerative disease. Picklo, M.J., Olson, S.J., Hayes, J.D., Markesbery, W.R., Montine, T.J. Brain Res. (2001) [Pubmed]
  2. Overall HIV-1 prevalence in pregnant women over-estimates HIV-1 in the predominantly rural population of Afar Region. Assefa, T., Davey, G., Dukers, N., Wolday, D., Worku, A., Messele, T., Tegbaru, B., Dorigo, W., Sanders, E.J. Ethiop. Med. J. (2003) [Pubmed]
  3. A seroprevalence study of camel brucellosis in three camel-rearing regions of Ethiopia. Teshome, H., Molla, B., Tibbo, M. Tropical animal health and production. (2003) [Pubmed]
  4. Mastitis in lactating camels (Camelus dromedarius) in Afar Region, north-eastern Ethiopia. Bekele, T., Molla, B. Berl. Munch. Tierarztl. Wochenschr. (2001) [Pubmed]
  5. Haematobium schistosomiasis among seminomadic and agricultural Afar in Ethiopia. Kloos, H., Polderman, A.M., Desole, G., Lemma, A. Tropical and geographical medicine. (1977) [Pubmed]
  6. New discoveries of Australopithecus at Maka in Ethiopia. White, T.D., Suwa, G., Hart, W.K., Walter, R.C., WoldeGabriel, G., de Heinzelin, J., Clark, J.D., Asfaw, B., Vrba, E. Nature (1993) [Pubmed]
  7. Cloning of the human aflatoxin B1-aldehyde reductase gene at 1p35-1p36.1 in a region frequently altered in human tumor cells. Praml, C., Savelyeva, L., Perri, P., Schwab, M. Cancer Res. (1998) [Pubmed]
  8. Characterization of the rat aflatoxin B1 aldehyde reductase gene, AKR7A1. Structure and chromosomal localization of AKR7A1 as well as identification of antioxidant response elements in the gene promoter. Ellis, E.M., Slattery, C.M., Hayes, J.D. Carcinogenesis (2003) [Pubmed]
  9. Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members. O'connor, T., Ireland, L.S., Harrison, D.J., Hayes, J.D. Biochem. J. (1999) [Pubmed]
  10. cDNA cloning, expression and activity of a second human aflatoxin B1-metabolizing member of the aldo-keto reductase superfamily, AKR7A3. Knight, L.P., Primiano, T., Groopman, J.D., Kensler, T.W., Sutter, T.R. Carcinogenesis (1999) [Pubmed]
  11. Molecular cloning, expression and catalytic activity of a human AKR7 member of the aldo-keto reductase superfamily: evidence that the major 2-carboxybenzaldehyde reductase from human liver is a homologue of rat aflatoxin B1-aldehyde reductase. Ireland, L.S., Harrison, D.J., Neal, G.E., Hayes, J.D. Biochem. J. (1998) [Pubmed]
  12. Regulation of aflatoxin B1-metabolizing aldehyde reductase and glutathione S-transferase by chemoprotectors. McLellan, L.I., Judah, D.J., Neal, G.E., Hayes, J.D. Biochem. J. (1994) [Pubmed]
  13. Stratigraphic, chronological and behavioural contexts of Pleistocene Homo sapiens from Middle Awash, Ethiopia. Clark, J.D., Beyene, Y., WoldeGabriel, G., Hart, W.K., Renne, P.R., Gilbert, H., Defleur, A., Suwa, G., Katoh, S., Ludwig, K.R., Boisserie, J.R., Asfaw, B., White, T.D. Nature (2003) [Pubmed]
  14. HIV-1 seroprevalence and subtypes in police recruits from Afar regional state, Ethiopia. Zewde, A., Bahiru, S., Sanders, E., Tilahun, T., Beyene, A., Alebachew, M., Schaap, A., Wolday, D., Rinke de Wit, T.F. Ethiop. Med. J. (2002) [Pubmed]
 
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