ArticleThe Journal of biological chemistry2002
Distinct retinoid metabolic functions for alcohol dehydrogenase genes Adh1 and Adh4 in protection against vitamin A toxicity or deficiency revealed in double null mutant mice.
Article in The Journal of biological chemistry, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 102 citations in OpenAlex.
- Therapeutics for Alcohol-Associated Liver Disease.Annual review of pharmacology and toxicology · 2026Review
- UK Biobank-Based Genetic and Proteomic Network Insights into Metabolic Dysfunction-Associated Steatotic Liver Disease Pathogenesis.International journal of molecular sciences · 2026Article
- Connective tissue profiling in keratinized and non-keratinized oral mucosa reveals distinct extracellular and intracellular features.Frontiers in cell and developmental biology · 2026Article
- SPP1+ tumor-associated macrophages define a high-risk subgroup and inform personalized therapy in hepatocellular carcinoma.Frontiers in oncology · 2025Article
- Autophagy and biotransformation affect sorafenib resistance in hepatocellular carcinoma.Computational and structural biotechnology journal · 2023Article
- Jejunal Transcriptomic Profiling for Differences in Feed Conversion Ratio in Slow-Growing Chickens.Animals : an open access journal from MDPI · 2021Article
- Alcohol in Psoriasis-From Bench to Bedside.International journal of molecular sciences · 2021Review
- Genome-wide pQTL analysis of protein expression regulatory networks in the human liver.BMC biology · 2020Article
- Regulating Retinoic Acid Availability during Development and Regeneration: The Role of the CYP26 Enzymes.Journal of developmental biology · 2020Review
- Assessment of liver cancer biomarkers.Gastroenterology and hepatology from bed to bench · 2020Review
- Genetics and functions of the retinoic acid pathway, with special emphasis on the eye.Human genomics · 2019Review
- Genes lost during the transition from land to water in cetaceans highlight genomic changes associated with aquatic adaptations.Science advances · 2019Article
- The prevalence of ADH1B and OPRM1 alleles predisposing for alcohol consumption are increased in the Hungarian psoriasis population.Archives of dermatological research · 2019Article
- Recent insights on the role and regulation of retinoic acid signaling during epicardial development.Genesis (New York, N.Y. : 2000) · 2019Review
- Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.Nature genetics · 2018Article
- Effects of low dose of ethanol on the senescence score, brain function and gene expression in senescence-accelerated mice 8 (SAMP8).Experimental and therapeutic medicine · 2017Article
- New insights and changing paradigms in the regulation of vitamin A metabolism in development.Wiley interdisciplinary reviews. Developmental biology · 2017Review
- Review
- Coelimination and Survival in Gene Network Evolution: Dismantling the RA-Signaling in a Chordate.Molecular biology and evolution · 2016Article
- Computational studies of human class V alcohol dehydrogenase - the odd sibling.BMC biochemistry · 2016Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The ability of class I alcohol dehydrogenase (ADH1) and class IV alcohol dehydrogenase (ADH4) to metabolize retinol to retinoic acid is supported by genetic studies in mice carrying Adh1 or Adh4 gene disruptions. To differentiate the physiological roles of ADH1 and ADH4 in retinoid metabolism we report here the generation of an Adh1/4 double null mutant mouse and its comparison to single null mutants. We demonstrate that loss of both ADH1 and ADH4 does not have additive effects, either for production of retinoic acid needed for development or for retinol turnover to minimize toxicity. During gestational vitamin A deficiency Adh4 and Adh1/4 mutants exhibit completely penetrant postnatal lethality by day 15 and day 24, respectively, while 60% of Adh1 mutants survive to adulthood similar to wild-type. Following administration of a 50-mg/kg dose of retinol to examine retinol turnover, Adh1 and Adh1/4 mutants exhibit similar 10-fold decreases in retinoic acid production, whereas Adh4 mutants have only a slight decrease. LD(50) studies indicate a large increase in acute retinol toxicity for Adh1 mutants, a small increase for Adh4 mutants, and an intermediate increase for Adh1/4 mutants. Chronic retinol supplementation during gestation resulted in 65% postnatal lethality in Adh1 mutants, whereas only approximately 5% for Adh1/4 and Adh4 mutants. These studies indicate that ADH1 provides considerable protection against vitamin A toxicity, whereas ADH4 promotes survival during vitamin A deficiency, thus demonstrating largely non-overlapping functions for these enzymes in retinoid metabolism.
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