Skip to Content
Merck
  • Pharmacological recruitment of aldehyde dehydrogenase 3A1 (ALDH3A1) to assist ALDH2 in acetaldehyde and ethanol metabolism in vivo.

Pharmacological recruitment of aldehyde dehydrogenase 3A1 (ALDH3A1) to assist ALDH2 in acetaldehyde and ethanol metabolism in vivo.

Proceedings of the National Academy of Sciences of the United States of America (2015-02-26)
Che-Hong Chen, Leslie A Cruz, Daria Mochly-Rosen
ABSTRACT

Correcting a genetic mutation that leads to a loss of function has been a challenge. One such mutation is in aldehyde dehydrogenase 2 (ALDH2), denoted ALDH2*2. This mutation is present in ∼ 0.6 billion East Asians and results in accumulation of toxic acetaldehyde after consumption of ethanol. To temporarily increase metabolism of acetaldehyde in vivo, we describe an approach in which a pharmacologic agent recruited another ALDH to metabolize acetaldehyde. We focused on ALDH3A1, which is enriched in the upper aerodigestive track, and identified Alda-89 as a small molecule that enables ALDH3A1 to metabolize acetaldehyde. When given together with the ALDH2-specific activator, Alda-1, Alda-89 reduced acetaldehyde-induced behavioral impairment by causing a rapid reduction in blood ethanol and acetaldehyde levels after acute ethanol intoxication in both wild-type and ALDH2-deficient, ALDH2*1/*2, heterozygotic knock-in mice. The use of a pharmacologic agent to recruit an enzyme to metabolize a substrate that it usually does not metabolize may represent a novel means to temporarily increase elimination of toxic agents in vivo.

MATERIALS
Product Number
Brand
Product Description

Eugenol, European Pharmacopoeia (EP) Reference Standard
Supelco
Eugenol, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Supelco
Methyl eugenol, analytical standard
Supelco
Eugenol, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Cinnamaldehyde, Vetec, reagent grade, 93%
Benzaldehyde, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Heptanal, ≥95%, FCC, FG
Supelco
Benzaldehyde, analytical standard
Sigma-Aldrich
Benzaldehyde, puriss. p.a., ≥99.0% (GC)
Sigma-Aldrich
Benzaldehyde, purified by redistillation, ≥99.5%
Sigma-Aldrich
Heptaldehyde, 95%
Sigma-Aldrich
Benzaldehyde, ReagentPlus®, ≥99%
Sigma-Aldrich
Cinnamaldehyde, natural, ≥95%, FG
Sigma-Aldrich
Eugenol, ≥98%, FCC, FG
Sigma-Aldrich
Methyl eugenol, ≥98%, FCC
Sigma-Aldrich
4-Allyl-1,2-dimethoxybenzene, 99%
Sigma-Aldrich
Benzaldehyde, natural, FCC, FG
Sigma-Aldrich
Eugenol, natural, ≥98%, FG
Sigma-Aldrich
Benzaldehyde, ≥98%, FG, FCC
Sigma-Aldrich
Eugenol, ReagentPlus®, 99%
Supelco
Eugenol, PESTANAL®, analytical standard
Supelco
Benzaldehyde, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Heptaldehyde, analytical standard
Supelco
trans-Cinnamaldehyde, analytical standard
Sigma-Aldrich
trans-Cinnamaldehyde, FCC, FG
Sigma-Aldrich
trans-Cinnamaldehyde, ≥99%
Sigma-Aldrich
trans-Cinnamaldehyde, 97%
Sigma-Aldrich
Decanal, ≥98% (GC), liquid
Sigma-Aldrich
Decanal, FCC, FG
Sigma-Aldrich
Decanal, natural, ≥97%, FG