Document Detail

Interactions of plant acetohydroxy acid isomeroreductase with reaction intermediate analogues: correlation of the slow, competitive, inhibition kinetics of enzyme activity and herbicidal effects.
MedLine Citation:
PMID:  8053906     Owner:  NLM     Status:  MEDLINE    
N-Hydroxy-N-isopropyloxamate (IpOHA) is known to inhibit extremely tightly (Ki of 22 pM) the bacterial acetohydroxy acid isomeroreductase (EC [Aulabaugh and Schloss (1990) Biochemistry 29, 2824-2830], the second enzyme of the branched-chain-amino-acid-biosynthetic pathway. Yet, although the same pathway exists in plant cells, this compound presents only very poor herbicidal action. Towards the goal of gaining a better understanding of this behaviour, we have studied the mechanism of interaction of this compound with a highly purified acetohydroxy acid isomeroreductase of plant origin, i.e. the spinach (Spinacia oleracea) chloroplast enzyme. IpOHA behaved as a nearly irreversible inhibitor of the enzyme. Encounter complex formation was very slow (association rate constant 1.9 x 10(3) M-1.s-1) and involved a single bimolecular step. Since inhibition was competitive with respect to acetohydroxy acid substrates, the time needed to achieve substantial (90%) inhibition in vitro of enzyme activity in the simultaneous presence of substrates and inhibitors was extremely long (for example of the order of hours at 1 microM IpOHA and 100 microM acetohydroxy acid substrates). Thus, under in vivo conditions, binding of the inhibitor may be so slow that it may delay considerably the time required for inhibition of the target enzyme. Simialr kinetic behaviour was observed with another reaction intermediate analogue described by Schulz, Spönemann, Köcher and Wengenmayer [(1988) FEBS Lett. 238, 375-378], 2-dimethyl-phosphinoyl-2-hydroxyacetic acid (Hoe 704), which displays a higher herbicide activity than IpOHA. The herbicidal potency of these two compounds appeared to be correlated with their rates of association with the plant acetohydroxy acid isomeroreductase, since the bimolecular rate constant for Hoe 704 (2.2 x 10(4) M-1.s-1) was higher than that for IpOHA.
R Dumas; C Cornillon-Bertrand; P Guigue-Talet; P Genix; R Douce; D Job
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  301 ( Pt 3)     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1994 Aug 
Date Detail:
Created Date:  1994-09-06     Completed Date:  1994-09-06     Revised Date:  2010-09-13    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  813-20     Citation Subset:  IM    
Unité Mixte de Recherche CNRS/Rhône-Poulenc (Unité associée au Centre National de la Recherche Scientifique, UM 41), Lyon, France.
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MeSH Terms
Alcohol Oxidoreductases / antagonists & inhibitors*,  metabolism
Binding, Competitive
Chloroplasts / enzymology
Chromatography, Gel
Herbicides / pharmacology*
Hydroxamic Acids / metabolism,  pharmacology
Ketol-Acid Reductoisomerase
Magnesium / metabolism
NADP / metabolism
Organophosphorus Compounds / metabolism,  pharmacology
Plants / enzymology*
Protein Binding
Spectrometry, Fluorescence
Reg. No./Substance:
0/Herbicides; 0/Hydroxamic Acids; 0/Organophosphorus Compounds; 125568-35-6/N-hydroxy-N-isopropyloxamate; 53-59-8/NADP; 7439-95-4/Magnesium; 91154-17-5/2-methylphosphinoyl-2-hydroxyacetic acid; EC 1.1.-/Alcohol Oxidoreductases; EC Reductoisomerase

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