Fungicides inhibiting dehydrogenases

The phenoxyquinolines are a recent addition to crop fungicides and only one compound has been described. LY214352, an experimental fungicide, inhibits a novel target, dihydro-orotate dehydrogenase (DHO-DH) in the pyrimidine biosynthesis pathway that catalyses the conversion of dihydro-orotate into orotic acid9 (Figure 4.13). 

Dithiocarbamate fungicides inhibit aldehyde dehydrogenase. In order to produce an amperometric biosensor with this enzyme also a bi-enzymatic system was designed with the enzyme diaphorase. Reaction of propiraialdehyde and NAD" in the presence of ADH produced NADH which could be detected via its reaction with hexacyanoferrate(in) by diaphorase. The changes of hexacyanoferrate (11) concentrations were monitored amperometrically with a Pt electrode or bi-amperometrically with two platinum electrodes. A bi-amperometric biosensor was also developed in screen-printed configuration with Pt-sputtered carbon paste In aU these biosensors both enzymes were immobilized in a poly(vinyl alcohol)-styrylpyridinium (PVA-SbQ) layer. 

Analysis by electron microscopy shows that Complex I from bovine heart, N. crassa, Y. lipolytica, and E. coli, can adopt a similar L shape structure, which spans the inner mitochondrial membrane with an arm extending into the matrix compartment [31, 32] (Fig. 13.1.2). A sub-domain representing part of this arm can be isolated that contains the FMN and retains NADH dehydrogenase activity coupled to reduction of ferricyanide (which is also an enzymic activity of intact Complex I). This activity is sensitive to the now superseded fungicide fenamino-sulf [33, 34]. Fenaminosulf is not a highly selective Complex I inhibitor, but its ability to inhibit ferricyanide reduction is unusual and defines its site of action... 

Several other biosensors for pesticide and toxic metal monitoring are also based on the inhibition of enzymes such as urease for heavy metals, tyrosinase for benzoic acid, thiourea and 2-mercaptoethanol, alcohol dehydrogenase for cyanides and heavy metal salts, amino oxidase for plant growth regulators, aldehyde dehydrogenase for fungicides, cytochrome c for cyanides, catalase for heavy metals, and peroxidase for cyanides and heavy metals. Thus, biosensors based on the inhibition of enzymes, suffer from false-positive results. Despite lack of selectivity, this type of biosensor is powerful when rapid toxicity screening is required. 

Aldehyde dehydrogenase (ADH) catalyzes the oxidation of various aldehydes using P-nicotinamide adenine dinucleotide (NAD" ) as a cofactor. The enzyme is inhibited by dithiocarbamate fungicides and this can be utilized to detect these pesticides in the environment. ... 

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