Acetolactate synthase inhibition

Maertens, K.D., C.L. Sprague, P.J. Tranel, and R.A. Hines (2004). Amaranthus hyridus populations resistant to triazine and acetolactate synthase-inhibiting herbicides. Weed Res., 44 21-26. 

Christopher, J.T., S.B. Powles, and J.A.M. Holtum (1992). Resistance to acetolactate synthase-inhibiting herbicides in annual ryegrass (Lolium rigidum) involves at least two mechanisms. Plant Physiol., 100 1909-1913. 

Sibony, M., A. Michel, H.U. Haas, B. Rubin, and K. Hurle (2001). Sulfometuron-resistant Amaranthus retroflexus Cross-resistance and molecular basis for resistance to acetolactate synthase-inhibiting herbicides. Weed Res., 41 509-522. 

White, A.D., M.D.K. Owen, R.G. Hartzler, and J. Cardina (2001). Common sunflower (Helianthus annuus) resistance to acetolactate synthase inhibiting herbicides. Resistant Pest Management. East Lansing, MI Michigan State University, 11 3-5. 

Zelaya, I.A. and M.D.A. Owen (2004). Evolved resistance to acetolactate synthase-inhibiting herbicides in common sunflower (Helianthus annuus), giant ragweed (Ambrosia trifida), and shattercane (Sorghum bicolor) in Iowa. Weed Sci., 52 538-548. 

Acetolactate synthase inhibition by imidazolinones and triazolopyrimidines, 460 sensitivity to sulfonylurea herbicides, 460 Acetolactate synthase gene activity and inheritance of resistance in tobacco, 461... 

D. C. Resistance to Acetolactate Synthase Inhibiting Herbicides, in Herbicide Resistance in Plants, Powles, S. B., Holtum, J. A. M. (Eds.), CRC Press, Boca Raton, FL, 1994, 83-139. 

Saika H, Horita J, Taguchi-Shiobara F, Nonaka S, Ayako NY, Iwakami S, Hori K, Matsumoto T, Tanaka T, Itoh T, Yano M, Kaku K, Shimizu T, Toki S (2014) A novel rice cytochrome P450 gene, CY-P72A31, confers tolerance to acetolactate synthase-inhibiting herbicides in rice and Arabidopsis. Plant Physiol 156 1232-1240... 

Acetolactate synthase inhibition by herbicides, 36,38 inhibition by sulfonylurea herbicides, 33,36,37/... 

Herbicides also inhibit 5- (9/-pymvylshikiniate synthase, a susceptible en2yme in the pathway to the aromatic amino acids, phenylalanine, tyrosine and tryptophan, and to the phenylpropanes. Acetolactate synthase, or acetohydroxy acid synthase, a key en2yme in the synthesis of the branched-chain amino acids isoleucine and valine, is also sensitive to some herbicides. Glyphosate (26), the sulfonylureas (136), and the imida2oles (137) all inhibit specific en2ymes in amino acid synthesis pathways. 

Fig. 3. Generation of propionyl-CoA from the isoleucine biosynthetic pathway. The intermediate 2-ketobutyrate can be decarboxylated by either the 2-oxoacid dehydrogenase complex or at low efficiency by the pyruvate dehydrogenase complex. Inhibition of the threonine deaminase by isoleucine and of the acetolactate synthase by herbicides are indicated with dashed arrows...

In AChE-based biosensors acetylthiocholine is commonly used as a substrate. The thiocholine produced during the catalytic reaction can be monitored using spectromet-ric, amperometric [44] (Fig. 2.2) or potentiometric methods. The enzyme activity is indirectly proportional to the pesticide concentration. La Rosa et al. [45] used 4-ami-nophenyl acetate as the enzyme substrate for a cholinesterase sensor for pesticide determination. This system allowed the determination of esterase activities via oxidation of the enzymatic product 4-aminophenol rather than the typical thiocholine. Sulfonylureas are reversible inhibitors of acetolactate synthase (ALS). By taking advantage of this inhibition mechanism ALS has been entrapped in photo cured polymer of polyvinyl alcohol bearing styrylpyridinium groups (PVA-SbQ) to prepare an amperometric biosensor for... 

A. Seki, F. Ortega, and J.L. Marty, Enzyme sensor for the detection of herbicides inhibiting acetolactate synthase. Anal. Lett. 29,1259—1271 (1996). 

There are several commercially available sulfonylurea herbicides that contain a 2-pyrimidine group <2006H(68)561>. These compounds, which function by inhibition of acetolactate synthase (ALS), an enzyme involved in the early stage of branched-chain amino acid synthesis, include sulfometuron-methyl 1095, primisulfuron-methyl 1096, chlorimuron-ethyl 1097, bensulfuron-methyl 1098, ethoxysulfuron 1099, nicosulfuron 1100, and pyrazosulfuron-ethyl 1101. Related nonsulfonylureas include the sulfide pyrftalid 1102 and the ether pyriminobac-methyl 1103. 

Inhibition of acetolactate synthase (ALS) [Acetohydroxy acid synthase (AHAS)] Sulfonylureas Imidazolinones T riazolopyrimidines Pyrimidinylthiobenzoates 2... 

As indicated in Fig. 24-17, pyruvate is the starting material for the formation of both l- and D-alanine and also the branched chain amino acids valine, leucine, and isoleucine.339,340 The chemistry of the reactions has been discussed in the sections indicated in the figure. The first step is catalyzed by the thiamin diphosphate-dependent acetohydroxyacid synthase (acetolactate synthase), which joins two molecules of pyruvate or one of pyruvate and one of 2-oxobutyrate (Fig. 24-17 Fig. 14-3).340a b In E. coli there are two isoenzymes encoded by genes ilv B and ilv HI. Both are regulated by feedback inhibition by valine, probably... 

What are the criteria for regarding a compound as a TS analog The observation that the binding affinity of an inhibitor is greater than that of a substrate, i.e., X, < XM, is insufficient as many potent inhibitors bind differently to an enzyme than the substrate examples are methotraxate, inhibiting dihydrofolate reductase (DHFR) X] = 0.15 pM (Werkheiser, 1961), and sulfonyl urea herbicides, inhibiting acetolactate synthase (ALS) at picomolar levels. 

Devine, M.D., M.A.S. Maries, and L.M. Hall (1991). Inhibition of acetolactate synthase in susceptible and resistant biotypes of Stellaria media. Pesticide Sci., 31 273-280. 

Sprague, C.L., E.W. Stoller, and L.M. Wax (1997c). Response of an acetolactate synthase (ALS)-resistant biotype of Amaranthus rudis to selected ALS-inhibiting and alternative herbicides. Weed Res., 37 93-101. 

Figure 1. Three chemical families known to exhibit herbicidal activity through the inhibition of acetolactate synthase. A. sulfonylurea (sulfometuron) B. imidazolinone (imazapyr) and C. A representative triazolopyrimidine.

Figure 5. Inhibition of barley acetolactate synthase by triazolopyrimidine.

In the 1950s and 1960s, Geigy and other firms developed a series of herbicides based on alkyl and dialkyl triazines, such as the root-herbicide atrazine (83)64. They are made by stepwise introduction of suitable nucleophiles into precursors. Other members are ametryn, the non-selective simazine (84) and the cyanuric chloride-derived methylthio triazine desmetryne (85) (Scheme 19). Chlorotoluron is 3-(3-chloro-p-toly 1 )-1,1-dimethylurea (86), a phenylurea herbicide. These products act on the photosynthetic pathway. Both 83 and 84 are used for weed control in maize65. Sulfonylureas such as the triazine chlorosulfone (87) inhibit the enzyme acetolactate synthase. They offer the major advantage of requiring no more than 10 to 20 g per hectare. 

The mode of their action consists in the acetolactate synthase (ALS) inhibition and, as a result, in the inhibition of the branched-chain amino acid biosynthesis from acetolactate (90MI1, 92MI7, 98MI4). Results of QSAR studies were published (03MI3). Another approach was used to analyze a model of inhibition of photosystem II (96MI1). 

One of the most effective classes of herbicide are the sulfonylureas. They are applied in quantities of no more than a few grams per hectare. The action of sulfonylureas is based on inhibition of acetolactate synthase (ALS) [9]. The fluorine-containing derivative Primsulfuron methyl has selectivity in the cultivation of maize [10]. 

Inhibits ALS activity by 50%. A good correlation exists between the herbicidal activity of sulfonylureas and their ability to inhibit acetolactate synthase (2). This in vitro assay using the target enzyme along with the three-dimensioFTI structure of the enzyme should aid in the generation of a substantial data base that can be used to design potent inhibitors. 

Second, a key enzyme or receptor in the pathway should be identified as the target. It is best to select enzymes whose products are important for several functions in the species. Cellular response to such a metabolic blockade should also be considered (e.g., cascading effects). Often end-product limitation results in more metabolites entering the pathway. After sufficient substrate accumulation, catalysis may occur even in the presence of an inhibitor (10). However, accumulation of toxic intermediates would prevent tTTTs cellular response and lead to death. Again using sulfonylureas as an example, acetolactate synthase is a common enzyme in the pathway for two essential amino acids rather than just one. Also, inhibition of acetolactate synthase leads to high levels of a-ketobutyrate which is thought to have deleterious effects (11). 

Acetohydroxyacid synthase, inhibition in plants, 66 Acetolactate synthase... 

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