Acetolactate synthase

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. 

The mechanistic chemistry of the acetolactate synthase and phosphoketolase reactions (shown below) is similar to that of the transketolase reaction (Figure 23.34). Write suitable mechanisms for these reactions. 

CrylAc protein Modified EPSPS Acetolactate synthase (csr-1) CrylllA, PVY coat protein CrylllA, PLRV repUcase Nitrilase, CrylAc protein... 

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). 

BOROHYDRIDE REDUCTION ACETAZOLAMIDE Acetic acid, autoprotolysis constant, AUTOPROTOLYSIS ACETOACETATE DECARBOXYLASE Acetoacetate decarboxylase reduction, BOROHYDRIDE REDUCTION ACETOLACTATE SYNTHASE Acetone,... 

Thiamin-dependent enzymes, ACETOLACTATE SYNTHASE BENZOYLFORMATE DECARBOXYLASE BRANCHED-CHAIN a-KETO ACID DEHYDROGENASE COMPLEX... 

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. 

Hydroxy-2-butanone (acetoin) is a characteristic constituent of butter flavour used for flavouring margarine and can be obtained as a by-product of molasses-based and lactic acid fermentations [49, 71]. The closely related 2,3-butanedione (diacetyl) has a much lower organoleptic threshold than acetoin and is an important strongly butter-like flavour compound in butter and other dairy products [72] in buttermilk, for instance, the diacetyl concentration is only about 2-4 mg [73]. a-Acetolactate (a-AL) is an intermediate of lactic acid bacteria mainly produced from pyruvate by a-acetolactate synthase. In most lactic acid bacteria, a-AL is decarboxylated to the metabolic end product acetoin by a-AL decarboxylase (ALDB) [71] (Scheme 23.5). 

Scheme 23.5 Metabolic pathways of lactic acid bacteria leading from pyruvate to a-acetolactate and acetoin and chemical diacetyl formation. ALS a-acetolactate synthase, ALDB a-acetolactate decarboxylase, DDH diacetyl dehydrogenase. (Adapted from [72])...

Branched Chain Amino Acid Biosynthesis. The branched chain amino acids, leucine, isoleucine and valine, are produced by similar biosynthetic pathways (Figure 2.11). In one pathway, acetolactate is produced from pyruvate and in the other acetohydroxybutyrate is produced from threonine. Both reactions are catalysed by the same enzyme that is known as both acetolactate synthase (ALS) and acetohy-droxy acid synthase (AHAS). 

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

Formation of a-ketols from a-oxo acids also starts with step b of Fig. 14-3 but is followed by condensation with another carbonyl compound in step c, in reverse. An example is decarboxylation of pyruvate and condensation of the resulting active acetaldehyde with a second pyruvate molecule to give R-a-acetolactate, a reaction catalyzed by acetohydroxy acid synthase (acetolactate synthase).128 Acetolactate is the precursor to valine and leucine. A similar ketol condensation, which is catalyzed by the same synthase, is... 

Acetohydroxy acid synthase (acetolactate synthase) 1-Deoxy-D-xylulose 5-phosphate synthase Transketolase ... 

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... 

Haughn, G., Smith, J., Mazur, B. Sommerville, C. (1988). Transformation with a mutant Arabidopsis acetolactate synthase gene renders tobacco resistant to sulfonylurea herbicides. Molecular and General Genetics 211, 266-71. 

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. 

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. 

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