Pyruvate Dehydrogenase Complex PDHc

The activity of the pyruvate dehydrogenase complex (PDHC) in mammals is altered by an enzyme-catalyzed phosphorylation (Chap. 12) of the complex... 

Pyruvate dehydrogenase complex (PDHC) deficiency and electron transport chain disorders are examples of mitochondrial energy disorders. The primary goal of treatment is to minimize acidosis. In prevention of lactic acidosis (especially in PDHC deficiency) glucose supply has to be limited. 

Transformation of pyruvate to acetyl-CoA is linked to glycolysis and to the Krebs cycle and oxidative phosphorylation. The pyruvate dehydrogenase complex (PDHc) catalyzes the oxidative decarboxylation of pyruvate and acetylation of coenzyme A (CoA) to acetyl-CoA. This enzyme has been viewed as a potential herbicide target [238], In the perspective of structural optimization of a potent new herbicide, He et al. synthesized a series of structures 307 [239-241], which were a priori designed to inhibit the PDHc. 

Pyruvate dehydrogenase complex (PDHC) is a multienzyme complex which, through a multistep reaction, provides acetyl-CoA for the... 

Recent observations (Carreau et al.,1977) allowed a parallel to be drawn with the hypothesis concerning the possible participation of the linoleic acid in the pyruvate dehydrogenase complex (PDHc). ... 

Pyruvate Dehydrogenase Complex (PDHc) 1,2,1 Function of PDHc... 

Scheme 1.1 Pivotal role of pyruvate dehydrogenase complex (PDHc)...

Murarka A, Clomburg JM, Moran S et al (2010) Metabolic analysis of wild-type Escherichia coli and a pyruvate dehydrogenase complex (PDHC)-deficient derivative reveals the role of PDHC in the fermentative metabolism of glucose. J Biol Chem 285 31548-31558... 

A detailed study of acylphosphinates and acylphosphonates showed that they were mechanism-based inhibitors of pyruvate dehydrogenase complex (PDHc) as analogues of pyruvate. However, these phosphinates and phosphonates were not active enough to be considered as herbicides [1-3]. As stated in Chap. 2, some 1-substituted alkylphosphonates IC and IG showed notable herbicidal activity. Furthermore, the substitution of R R, R, R" and Y in phosphonate lo could be directly relevant to their herbicidal activity. Among the 1-substituted alkylphosphonates lA-IC, IC-22 (clacyfos) was found to be most eflFective against broadleaf weeds as a competitive inhibitor of PDHc (Scheme 3.1) [4]. This result prompted us to study continually on the design of novel PDHc inhibitors as potential herbicides. 

He HW, Peng H, Wang T et al (2013) a-(Substituted-phenoxyacetoxy)-a-heterocyclylmethyl-phosphonates synthesis, herbicidal activity, inhibition on pyruvate dehydrogenase complex (PDHc), and application as postemergent herbicide against broadleaf weeds. J Agric Food Chem 61 2479-2488... 

Pyruvate dehydrogenase complex (PDHc) is one of the most important oxido-reductases in living organisms. It catalyzes the oxidative decarboxylation of pyruvate to form acetyl CoA, which is a pivotal process in cellular metabolism. PDHc has been reported as a potential target enzyme affected by some herbicidally active compounds. Regrettably, the PDHc inhibitors reported so far were not as active as other commercial herbicides. Therefore PDHc as a potential herbicidal target needs further investigation. 

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