About
Contact
Help
Sending publications
How to publish
Advanced Search
View Item 
  •   Home
  • Facultad de Ciencias Químicas y Farmacéuticas
  • Artículos de revistas
  • View Item
  •   Home
  • Facultad de Ciencias Químicas y Farmacéuticas
  • Artículos de revistas
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Browse byCommunities and CollectionsDateAuthorsTitlesSubjectsThis CollectionDateAuthorsTitlesSubjects

My Account

Login to my accountRegister
Biblioteca Digital - Universidad de Chile
Revistas Chilenas
Repositorios Latinoamericanos
Tesis LatinoAmericanas
Tesis chilenas
Related linksRegistry of Open Access RepositoriesOpenDOARGoogle scholarCOREBASE
My Account
Login to my accountRegister

Mutations in mitochondrial aldehyde dehydrogenase (ALDH2) change cofactor affinity and segregate with voluntary alcohol consumption in rats

Artículo
Thumbnail
Open/Download
IconSAPAG_2003.pdf (6.635Mb)
Publication date
2003-08
Metadata
Show full item record
Cómo citar
Sapag, Amalia
Cómo citar
Mutations in mitochondrial aldehyde dehydrogenase (ALDH2) change cofactor affinity and segregate with voluntary alcohol consumption in rats
.
Copiar
Cerrar

Author
  • Sapag, Amalia;
  • Tampier de Jong, Lutske;
  • Prieto, A.;
  • Quintanilla González, María Elena;
  • Moncada, C.;
  • Israel Jacard, Yedy;
Abstract
Genetic factors influence alcohol consumption and alcoholism. A number of groups have bred alcohol drinker and non drinker rat strains, but genetic determinants remain unknown. The University of Chile rat lines UChA (low drinkers) and UChB (high drinkers) display differences in the relative K-m for NAD(+) of mitochondrial aldehyde dehydrogenase (ALDH2) but no V-max differences. The relative K-m differences may be due to mitochondrial changes or to genetic differences coding for ALDH2. We investigated whether there are differences in the coding regions of ALDH2 cDNA in these lines and whether the AIdh2 genotype predicts the phenotype of alcohol consumption and the K-m of ALDH2 for NAD(+). Liver cDNA was prepared, and the Aldh2 transcript was amplified, cloned and sequenced. Genotyping was conducted by DNA amplification and restriction enzyme digestion. When compared to Aldh2(1) of Sprague-Dawley, 94% of the UChA (low drinker) rats (n = 61), presented a mutation that changes Gln(67) to Arg in the mature enzyme (allele referred to as Aldh2(2)). In UChB (high drinker) rats (n = 69), 58% presented the Aldh2(1) allele, while 42% presented the Gln(67)Arg change plus a second mutation that changed GIu(479) to Lys (allele Aldh2(3)). The Aldh2(2) allele was absent in high drinker rats. Rats of different AIdh2 genotypes displayed marked phenotypic differences in both ethanol consumption (g/kg/day; means +/- SE): (AIdh2(1)/ Aldh2(1)) = 5.7 +/- 0.2, (Aldh2(2)/Aldh2(2)) = 0.9 +/- 0.2 and (Aldh2(3)/Aldh2(3)) = 4.6 +/- 0.2; and K(m)s for NAD(+) of 43 +/- 3 muM, 132 +/- 13 muM and 41 +/- 2 mum, respectively (Aldh2(2) versus Aldh2(1) or Aldh2(3); P < 0.0001 for both phenotypes). Overall, the data show that alleles of Aldh2 strongly segregate with the phenotype of ethanol consumption and the relative K-m for NAD(+) of ALDH2. Bases mutated suggest that non drinker Aldh2(2) is ancestral with regard to the coding changes in either Aldh2(1) or Aldh2(3), variants which would allow ethanol consumption and may provide an evolutionary advantage by promoting calorie intake from fermented products along with carbohydrates.
General note
Artículo de publicación ISI
Identifier
URI: https://repositorio.uchile.cl/handle/2250/121284
ISSN: 0960-314X
Quote Item
PHARMACOGENETICS 13 (8): 509-515
Collections
  • Artículos de revistas
xmlui.footer.title
31 participating institutions
More than 73,000 publications
More than 110,000 topics
More than 75,000 authors
Published in the repository
  • How to publish
  • Definitions
  • Copyright
  • Frequent questions
Documents
  • Dating Guide
  • Thesis authorization
  • Document authorization
  • How to prepare a thesis (PDF)
Services
  • Digital library
  • Chilean academic journals portal
  • Latin American Repository Network
  • Latin American theses
  • Chilean theses
Dirección de Servicios de Información y Bibliotecas (SISIB)
Universidad de Chile

© 2020 DSpace
  • Access my account