Inhibition of acetolactate synthase

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... 

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. 

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.

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]. 

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). 

A great number of herbicides that work through the inhibition of acetolactate synthase (ALS) have been commercialized. They belong to four chemical groups sulfonylureas (23), triazolopyrimidines (2), imidazolinones (5), and pyrimidinyloxybenzoic analogues (3). (The number of active ingredients in parentheses is taken from The Pesticide Manual.) Also in this case, potent herbicides were developed (e.g., chlorsulfuron) before the site of action was found. 

The same is true in the case of imazaquin and chlorimuron-ethyl. It is well known that these two herbicides have the same mode of action (, ), namely blocking the biosynthesis of branched chain amino acids by inhibition of acetolactate synthase (ALS) correspondingly, the response patterns are very similar. 

I Amidosulfuron H Inhibits synthesis of branched AA by inhibition of acetolactate synthase >5000 (R, M)... 

Triazine herbicides and quinoclamine, having the mode of action in inhibition of PS II (Photosynthesis at photosystem II) had low variability on sensitivities in different algal taxa. On tiie other hand. Amide herbicide such as Pretilachlor and Cafenstrole as well as sulfonylurea herbicides of bensulfiironmethyl and imazosulfuron had great variability on sensitivities in different algal taxa. These herbicide have in other the mode of action in inhibition of cell division or in inhibition of acetolactate synthase rather tiian in inhibition of PS II. Carbamate herbicide showed relatively low toxicity on algae. Daimuron and bentazone exhibit low toxicity on all tire tested species (Figure 3). 

The compounds are applied pre- or postemergence, and all are mobile in phloem, " especially imazapyr which is well translocated to roots following foliar application. In roots and apical meristems, cell division is prevented due to the inhibition of acetolactate synthase limiting production of valine, leucine, and isoleucine. 

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