Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inhibition of branched-chain amino acid (BCAA) biosynthesis was evaluated in pea plants in relation to the ability for induction of fermentative metabolism under aerobic conditions. Chlorsulfuron and imazethapyr (inhibitors of acetolactate synthase, ALS, EC 4.1.3.18) produced a strong induction of pyruvate decarboxylase (PDC, EC 4.1.1.1) and alcohol dehydrogenase (ADH, EC 1.1.1.1) activities and a lesser induction of lactate dehydrogenase (LDH, EC 1.1.1.27) and alanine aminotransferase (AlaAT, EC 2.6.1.2) activities in roots. Inhibition of the second enzyme of the BCAA biosynthesis (ketol-acid reductoisomerase, KARI, EC 1.1.1.86) by Hoe 704 (2-dimethylphosphinoyl-2-hydroxyacetic acid) and CPCA (1,1-cyclopropanedicarboxylic acid) enhanced fermentative enzyme activities including PDC, ADH, and AlaAT. Fermentative metabolism induction occurring with ALS- and KARI-inhibitors was related to a higher expression of PDC. In the case of KARI inhibition, it is proposed that fermentation induction is due to an inhibition of ALS activity resulted from an increase in acetolactate concentration. Fermentative metabolism induction in roots, or at least ethanolic fermentation, appeared to be a general physiological response to the BCAA biosynthesis inhibition.
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PMID:Fermentative metabolism is induced by inhibiting different enzymes of the branched-chain amino acid biosynthesis pathway in pea plants. 1615 77

Acetolactate synthase (ALS; EC 4.1.3.18) and ketol-acid reductoisomerase (KARI; EC 1.1.1.86) are two consecutive enzymes in the biosynthesis of branched-chain amino acids. Several commercial herbicides inhibit ALS as their primary site of action. KARI has also attracted attention as a potential target for herbicides. Although potent and selective inhibitors of KARI have been discovered, these inhibitors display less herbicidal activity than ALS-inhibiting herbicides. To obtain a better understanding of these findings, we have compared the physiological effects induced in pea plants after KARI or ALS inhibition. Although, both types of inhibitors induce growth arrest and photosynthesis inhibition, plant death occurs more rapidly under ALS inhibition than KARI inhibition. Carbohydrates accumulated in the leaves and roots following treatments with both inhibitors. The carbohydrate accumulation in the leaves occurred as a consequence of a decrease in sink strength. In contrast, the free amino acid content was only affected through ALS inhibition. These results indicate that although KARI and ALS inhibition block the same biosynthetic pathway and exert common effects on carbon metabolism, nitrogen metabolism is more affected via ALS than KARI inhibition. Thus, metabolic alterations in nitrogen metabolism induced through ALS inhibitors might contribute to the increased efficacy of these chemicals as herbicides.
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PMID:Branched-chain amino acid biosynthesis inhibitors: herbicide efficacy is associated with an induced carbon-nitrogen imbalance. 2339 88