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Titre du document / Document title

Allosteric inhibition of human liver aldehyde dehydrogenase by the isoflavone prunetin

Auteur(s) / Author(s)

SHEIKH S. (1) ; WEINER H. (1) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Department of Biochemistry, Purdue University, West Lafayette, IN 47907-1153, ETATS-UNIS

Résumé / Abstract

Isoflavonoid derivatives including prunetin (4',5-dihydroxy-7-methoxyisoflavone) were shown to be potent inhibitors of human aldehyde dehydrogenases (Keung W-M and Vallee BL, Proc Natl Acad Sci USA 90: 1247-1251, 1993). The inhibition reaction was reinvestigated using recombinantly expressed human aldehyde dehydrogenases. The kinetic analyses showed that prunetin inhibits competitively against both NAD and propionaldehyde with the mitochondrial and cytoplasmic enzymes. The Ki value for the mitochondrial enzyme was much lower than for the cytoplasmic enzyme. A mixed pattern of inhibition was obtained with the mitochondrial enzyme in the presence of Mg2+. Only one mole of prunetin binds per mole of tetrameric mitochondrial enzyme, which remains unaltered in the presence of Mg2+. Prunetin did not displace NADH from the enzyme-NADH complex. Propionaldehyde did not reverse the loss of fluorescence obtained due to enzyme-prunetin complex formation, indicating that prunetin may not be interacting at the substrate site. The esterase activity of the mitochondrial enzyme was also inhibited by prunetin in a competitive manner. The replacement of lysine 192 by glutamine resulted in a mutant with a 20% kcat and a 100-fold increase in the Km for NAD compared with the native enzyme. However, the Ki value of prunetin against NAD was similar to that observed with the native enzyme. Prunetin, even at a very high concentration, was not an inhibitor of alcohol and malate dehydrogenase. It was concluded that prunetin may act as an allosteric inhibitor of aldehyde dehydrogenase.

Revue / Journal Title

Biochemical pharmacology    ISSN  0006-2952   CODEN BCPCA6 

Source / Source

1997, vol. 53, no4, pp. 471-478 (31 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1958) (Revue)

Mots-clés anglais / English Keywords

Isoflavone derivatives

;

Flavonoid

;

Enzyme inhibitor

;

Kinetics

;

Allosteric inhibitor

;

Competitive inhibition

;

NAD

;

Propanal

;

Biological fixation

;

Magnesium Cations

;

Substrate

;

NADH

;

Enzymatic activity

;

In vitro

;

Mitochondria

;

Plant origin

;

Oriental medicine

;

Leguminosae

;

Liver

;

Human

;

Aldehyde dehydrogenase (NAD+)

;

Dicotyledones

;

Angiospermae

;

Spermatophyta

;

Oxidoreductases

;

Enzyme

;

Mots-clés français / French Keywords

Isoflavone dérivé

;

Flavonoïde

;

Inhibiteur enzyme

;

Cinétique

;

Inhibiteur allostérique

;

Inhibition compétitive

;

NAD

;

Propanal

;

Fixation biologique

;

Magnésium Cation

;

Substrat

;

NADH

;

Activité enzymatique

;

In vitro

;

Mitochondrie

;

Origine végétale

;

Médecine orientale

;

Leguminosae

;

Foie

;

Homme

;

Aldehyde dehydrogenase (NAD+)

;

Prunetine

;

Radix puerariae

;

Dicotyledones

;

Angiospermae

;

Spermatophyta

;

Oxidoreductases

;

Enzyme

;

Mots-clés espagnols / Spanish Keywords

Flavonoide

;

Inhibidor enzima

;

Cinética

;

Inhibidor alostérico

;

Inhibición competitiva

;

NAD

;

Propanal

;

Fijación biológica

;

Magnesio Cation

;

Substrato

;

NADH

;

Actividad enzimática

;

In vitro

;

Mitocondria

;

Origen vegetal

;

Medicina oriental

;

Leguminosae

;

Hígado

;

Hombre

;

Aldehyde dehydrogenase (NAD+)

;

Dicotyledones

;

Angiospermae

;

Spermatophyta

;

Oxidoreductases

;

Enzima

;

Localisation / Location

INIST-CNRS, Cote INIST : 1418, 35400006450572.0040

Nº notice refdoc (ud4) : 2618386



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