Cellular targets dehydrogenase

Several other cellular target proteins for the reactive metabolite of paracetamol have also been detected and identified, namely, formyl tetrahydrofolate dehydrogenase, glyceralde-hyde-3-phosphate dehydrogenase (GAPDH), and GSH transferase, all cytosolic proteins. 

Function of mitochondria is also commonly monitored as an indicator of cellular toxicity. Mitochondrial uptake and retention of the fluorescent dye, rhodamine 123, can be visualized microscopically. Biochemical measurements of mitochondrial function include the ATP-ADP ratio and dehydrogenase activity with MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), which yields a colored formazan product upon reduction. The dye, neutral red (3-amino-7-dimethyl-amino-2-methylphenazine hydrochloride), targets lysosomes, and its retention is inversely related to cytotoxicity. Commercially available versions of the MTT and neutral red assays have been adapted to microtiter plate formats to provide highly efficient screening assays. Examples of how cell-type-specific functions can be followed as indicators of cell toxicity are included in Table 8.1. 

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. 

---