Aldehyde Dehydrogenase (ALDH)

Aldehyde dehydrogenases (ALDH, EC are a group of enzymes that catalyze the oxidation (dehydrogenation) of aldehydes to carboxylic acids, an action also performed by xanthine oxidase (XO) and aldehyde oxidase (AO).

The aldehyde cinnamaldehyde commonly used as a food flavoring is rapidly oxidized by aldehyde dehydrogenases into the carboxylic acid cinnamic acid.

Cinnamaldehyde AO Cinnamic acid
Cinnamaldehyde.gif —-> Cinnamic-acid.gif

Inhibitors and Inducers

Potent Inhibitors Strength Dosage Verified in Man
Calcium carbimide ? ? ?
Citral [5] 55 mM[6]1 ? ?
Daidzein (in Kudzu) ? ? ?
Daidzin(in Kudzu) Ineffective in hamsters [3]2 ? ?
Diethyl disulfide (in durian fruit) 81.5% in vitro[7] 1.1 ppm ?
Disulfiram ? ? Yes
Durian fruit extract 70% in vitro[7] 0.33 ppm ?
Gallic Acid ? ? ?
Phenethyl isothiocyanate (in cabbage) 70% in rats [1] ? ?
Semicarbazide ? ? ?
Moderate Inhibitors Strength Dosage Verified in Man
Caffeine[4] Moderate ? No3
Kudzu (contains Daidzin) ? ? ?
Soy isoflavones (contains Daidzein, similar to Daidzin) ? ? ?
Theophylline[4] Moderate ? No4
Weak Inhibitors Strength Dosage Verified in Man
Anisaldehyde ? ? ?
Benzaldehyde ? ? ?
Glycerin ? ? ?
Inducers (Unknown Potency) Strength Dosage Verified in Man
Black pepper ? ? ?
Capsaicin ? ? ?
Isosafrole ? ? ?
Piperine ? ? ?
Safrole ? ? ?

ALDH Action Duplicated By P450 Enzymes

Cytochrome P450 enzymes can oxidize certain aldehydes to carboxylic acids, performing an action similar to that of ALDH.[2]

In several tests the aldehyde 4-hydroxynonenal was successfully converted to its carboxylic acid using cytochrome P450 enzymes.[2]

The human cytochrome P450 enzymes enzymes catalyzed the reduction reaction in this order of effectiveness:

CYP2B6 > CYP3A4 > CYP1A2 > CYP2J2 [2]

Human CYP2E1 did not catalyze this reaction. [2]

1. J Pharmacol Exp Ther. 1995 Oct;275(1):79-83.
Phenethyl isothiocyanate, a new dietary liver aldehyde dehydrogenase inhibitor; Lindros KO, Badger T, Ronis M, Ingelman-Sundberg M, Koivusalo M; Biomedical Research Center, Alko Group Ltd., Helsinki, Finland; PubMed PMID: 7562599
2. Amunom I, Dieter LJ, Tamasi V, Cai J, Conklin DJ, Srivastava S, Martin MV, Guengerich FP, Prough RA.
Cytochromes P450 catalyze the reduction of α,β-unsaturated aldehydes; Department of Biochemistry and Molecular Biology, The University of Louisville School of Medicine , Louisville, KY 40292, USA; Chem Res Toxicol. 2011 Aug 15;24(8):1223-30. doi: 10.1021/tx200080b. Epub 2011 Jul 29; PubMed PMID: 21766881
3. Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8990-3.
Daidzin suppresses ethanol consumption by Syrian golden hamsters without blocking acetaldehyde metabolism. Keung WM, Lazo O, Kunze L, Vallee BL.; Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, MA 02115, USA. PubMed PMID: 7568058
4. Salivary aldehyde dehydrogenase—reversible oxidation of the enzyme and its inhibition by caffeine, investigated using fluorimetric method.
Wierzchowski J, Pietrzak M, Szelag M, Wroczyński P. PubMed PMID: 18154860
5. The metabolism of 3,7-dimethyl-2,6-octadienal (citral) in rat hepatic mitochondrial and cytosolic fractions. Interactions with aldehyde and alcohol dehydrogenases.
Boyer CS, Petersen DR. PubMed PMID: 1673427
6. Molecular cloning and oxidative modification of human lens ALDH1A1: implication in impaired detoxification of lipid aldehydes.
Xiao T, Shoeb M, Siddiqui MS, Zhang M, Ramana KV, Srivastava SK, Vasiliou V, Ansari NH. PubMed PMID: 19296407
7. Inhibition of aldehyde dehydrogenase enzyme by durian (Durio zibethinus Murray) fruit extract