Imidazolinones metabolism

ALS is also inhibited by a number of compounds which are structurally unrelated to the sulfonylureas. These include two other classes of herbicides the imidazolinones (5) and the triazolopyrimidines (Hawkes, T.R. Howard, J.L. Pontin, S.E. In Herbicides and Plant Metabolism, in press). LaRossa et al. have speculated on why ALS is such an effective target for so many inhibitors (6). Blocking ALS leads to the buildup of the toxic substrate a-ketobutyrate. The elevated levels of this metabolite combined with the reduced levels of the branched chain amino acids appear to make the inhibition of ALS a particularly lethal event. 

The imidazolinone herbicides (Table 2.3.1) are a family of six compounds that were discovered and developed by American Cyanamid Corporation. Readers may obtain comprehensive and detailed information in The Imidazolinone Herbicides [1], a book authored by the researchers who discovered and developed the herbicides. The herbicides as a class are broad spectrum and are active both pre-and postemergence. Imidazolinones are absorbed and moved through both xylem and phloem, eventually accumulating in the meristematic tissue. Activity is characterized by rapid cessation of growth followed by plant death days or weeks after treatment. Selectivity is based most often on metabolic inactivation except for selection-developed target site based resistance. 

The structural features of imidazolinones important for target site and herbicide activity have been summarized [11-14]. The orientation of the imidazolinone ring ortho to the acid equivalent is critical. Derivatives of the acid equivalent are herbicidally active if they can be metabolized to the acid either in the soil or in the plant. Likewise, tricyclic derivatives such as 4 are pro-herbicides that must be metabolized to the acid-imidazolinone form. 

NA had also a stimulatory effect on the oxidative metabolism of the herbicide bentazone. Microsomal preparations of etiolated shoots from maize, which had received a seed treatment with NA, showed activity of a bentazone hydroxylase, which was not detectable in extracts from controls without safener pre-treatment [35]. Also, the improved tolerance of maize to the imidazolinone AC263222 after NA seed treatment could be related to enhanced AC 263222 hydroxylation by stimulation of a cytochrome P450 monooxygenase [31]. 

Little information has been published about the l,2,4-triazolo[l,5-a]-pyrimidines. Their adverse effects on soybean cell growth are reversed by added valine, leucine, and isoleucine inhibition of plant ALS is associated with noncovalent binding of the inhibitor.Similarly, preliminary evidence shows that pyrimidinyl oxobenzoates are potent inhibitors of ALS. " Tobacco and soybean cell lines insensitive to triazolopyrimidines are also insensitive to sulfonylureas and imidazolinones, suggesting that all three classes of inhibitors have overlapping binding sites on ALS. Herbi-cidal selectivity for triazolopyrimidines in crop varieties results from differential uptake and metabolism. ... 

Acetolactate synthase (ALS) is the enzyme target site of the sulfonyl-ureas. In common with the imidazolinone aryl carboxylates, these herbicides inhibit valine and isoleucine biosynthesis. The imidazolinones are exemplified by Assert (8), which consists of a mixture of m- and p-isomers. The selectivity of ALS inhibitors invariably can be accounted for by differential metabolism or uptake or related phenomena rather than by any significant inherent difference in the properties of the ALS enzymes of crop and weed species. Assert is another example of a herbicide activated in plants by deesterification to the phytotoxic acid, and susceptible species such as Avena fatua (wild oat) are unable to metabolize the molecule further. Facile ring-methyl hydroxylation to the m- and p-benzyl alcohols, however, followed by glycosylation confers tolerance to maize and wheat." ... 

---