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Proc Natl Acad Sci U S A. Feb 15, 1993; 90(4): 1247–1251.

Daidzin: a potent, selective inhibitor of human mitochondrial aldehyde dehydrogenase.


Human mitochondrial aldehyde dehydrogenase (ALDH-I) is potently, reversibly, and selectively inhibited by an isoflavone isolated from Radix puerariae and identified as daidzin, the 7-glucoside of 4',7-dihydroxyisoflavone. Kinetic analysis with formaldehyde as substrate reveals that daidzin inhibits ALDH-I competitively with respect to formaldehyde with a Ki of 40 nM, and uncompetitively with respect to the coenzyme NAD+. The human cytosolic aldehyde dehydrogenase isozyme (ALDH-II) is nearly 3 orders of magnitude less sensitive to daidzin inhibition. Daidzin does not inhibit human class I, II, or III alcohol dehydrogenases, nor does it have any significant effect on biological systems that are known to be affected by other isoflavones. Among more than 40 structurally related compounds surveyed, 12 inhibit ALDH-I, but only prunetin and 5-hydroxydaidzin (genistin) combine high selectivity and potency, although they are 7- to 15-fold less potent than daidzin. Structure-function relationships have established a basis for the design and synthesis of additional ALDH inhibitors that could both be yet more potent and specific.

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  • Goedde HW, Agarwal DP. Pharmacogenetics of aldehyde dehydrogenase (ALDH). Pharmacol Ther. 1990;45(3):345–371. [PubMed]
  • Goedde HW, Agarwal DP. Polymorphism of aldehyde dehydrogenase and alcohol sensitivity. Enzyme. 1987;37(1-2):29–44. [PubMed]
  • Yoshida A, Huang IY, Ikawa M. Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals. Proc Natl Acad Sci U S A. 1984 Jan;81(1):258–261. [PMC free article] [PubMed]
  • Agarwal DP, Harada S, Goedde HW. Racial differences in biological sensitivity to ethanol: the role of alcohol dehydrogenase and aldehyde dehydrogenase isozymes. Alcohol Clin Exp Res. 1981 Jan;5(1):12–16. [PubMed]
  • Ohmori T, Koyama T, Chen CC, Yeh EK, Reyes BV, Jr, Yamashita I. The role of aldehyde dehydrogenase isozyme variance in alcohol sensitivity, drinking habits formation and the development of alcoholism in Japan, Taiwan and the Philippines. Prog Neuropsychopharmacol Biol Psychiatry. 1986;10(2):229–235. [PubMed]
  • Banys P. The clinical use of disulfiram (Antabuse): a review. J Psychoactive Drugs. 1988 Jul-Sep;20(3):243–261. [PubMed]
  • Neims AH, Coffey DS, Hellerman L. A sensitive radioassay for sulfhydryl groups with tetraethylthiuram disulfide. J Biol Chem. 1966 Jul 10;241(13):3036–3040. [PubMed]
  • Ikawa M, Impraim CC, Wang G, Yoshida A. Isolation and characterization of aldehyde dehydrogenase isozymes from usual and atypical human livers. J Biol Chem. 1983 May 25;258(10):6282–6287. [PubMed]
  • Hempel J, Pietruszko R, Fietzek P, Jörnvall H. Identification of a segment containing a reactive cysteine residue in human liver cytoplasmic aldehyde dehydrogenase (isoenzyme E1). Biochemistry. 1982 Dec 21;21(26):6834–6838. [PubMed]
  • Vallari RC, Pietruszko R. Human aldehyde dehydrogenase: mechanism of inhibition of disulfiram. Science. 1982 May 7;216(4546):637–639. [PubMed]
  • Blatter EE, Tasayco ML, Prestwich G, Pietruszko R. Chemical modification of aldehyde dehydrogenase by a vinyl ketone analogue of an insect pheromone. Biochem J. 1990 Dec 1;272(2):351–358. [PMC free article] [PubMed]
  • MacKerell AD, Jr, Vallari RC, Pietruszko R. Human mitochondrial aldehyde dehydrogenase inhibition by diethyldithiocarbamic acid methanethiol mixed disulfide: a derivative of disulfiram. FEBS Lett. 1985 Jan 1;179(1):77–81. [PubMed]
  • Vallari RC, Pietruszko R. Kinetic mechanism of the human cytoplasmic aldehyde dehydrogenase E1. Arch Biochem Biophys. 1981 Nov;212(1):9–19. [PubMed]
  • Sidhu RS, Blair AH. Human liver akdehyde dehydrogenase. Kinetics of aldehyde oxidation. J Biol Chem. 1975 Oct 10;250(19):7899–7904. [PubMed]
  • Price KR, Fenwick GR. Naturally occurring oestrogens in foods--a review. Food Addit Contam. 1985 Apr-Jun;2(2):73–106. [PubMed]
  • Akiyama T, Ishida J, Nakagawa S, Ogawara H, Watanabe S, Itoh N, Shibuya M, Fukami Y. Genistein, a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem. 1987 Apr 25;262(12):5592–5595. [PubMed]
  • Okura A, Arakawa H, Oka H, Yoshinari T, Monden Y. Effect of genistein on topoisomerase activity and on the growth of [Val 12]Ha-ras-transformed NIH 3T3 cells. Biochem Biophys Res Commun. 1988 Nov 30;157(1):183–189. [PubMed]
  • Lu XR, Gao E, Xu LZ, Li HZ, Kang B, Chen WN, Chen SM, Chai XS. Puerarin beta-adrenergic receptor blocking effect. Chin Med J (Engl) 1987 Jan;100(1):25–28. [PubMed]
  • Cromlish JA, Flynn TG. Identification of pig brain aldehyde reductases with the high-Km aldehyde reductase, the low-Km aldehyde reductase and aldose reductase, carbonyl reductase, and succinic semialdehyde reductase. J Neurochem. 1985 May;44(5):1485–1493. [PubMed]
  • Hoffman PL, Wermuth B, von Wartburg JP. Human brain aldehyde reductases: relationship to succinic semialdehyde reductase and aldose reductase. J Neurochem. 1980 Aug;35(2):354–366. [PubMed]

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