Molinate microsomes

Molinate has a low toxicity to rats, oral LDso=720 mg/kg, and is rapidly metabolized by plants to CO2 (1) (5) and naturally occurring plant constituents (1). Molinate is also readily metabolized by soil microorganisms (6). After incubation of molinate with Bacillus sp. 24, Nocardia sp. 119, and Micrococcus sp. 22r which were isolated from Russian garden soils and rice field drains (7,8), it was found that molinate was completely degraded into various hydroxy and oxidized products in the medium. Molinate can be metabolized to its corresponding sulfoxide in the mouse in vivo and by the microsome-NADPH system of mouse liver (9, 10). Hubbell et al. (11) and DeBaun et al. (12) also found molinate sulfoxide along with other polar and nonpolar metabolites in rat urine. 

Molinate Metabolism in Carp Hepatic Mixed-function Oxidase System. Incubation of molinate with carp liver microsomes produced four major organosoluble metabolites (molinate sulfoxide, 3- and 4-hydroxy molinate, and keto HMI). Parameters affecting... 

Figure 3. Effect of temperature on conversion of molinate to its sulfoxide by carp liver microsomal mfo (liver microsomal protein 6 mg/mL, pH 7.4, NADPH 3 mg incubated for 15 min)...

Figure 6. Chromatographic pattern for carp liver microsomal 14C-labeled organo-soluble metabolites of [ring-14C]-molinate. Incubation was conducted under standard conditions for one hr m number represents metabolite code.

In water containing fish, 4-keto molinate constituted 36.8% of all organosoluble metabolites 4 days after molinate addition. However, in the in vitro microsomal mixed-function oxidase system 4-hydroxy molinate was a principal metabolite (14.3%) and 4-keto molinate represented only 0.16% of the total metabolites. Keto-HMI (2.71%) also constituted a substantial proportion of the identified metabolites. 

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