Oxidative Dissimilation of Urocanate

Ichihara et d. (268-270) reported that urocanate is oxidized by an enzyme system found in liver and the bacterium, Psevdommas aeruginosa. The enzymes from both sources have been considerably purified by isoelectric precipitation, ammonium sulfate fractionation, and adsorption and elution from calcium phosphate gel. The d ree of enrichment cannot be determined from the published data. The oxidative activity, usually, is markedly increased by addition of EDTA. 

Study of the reaction with these enzyme preparations have indicated a ratio of oxygen absorption to urocanate decomposition of mole per mole. Products of the oxidative reaction reported to have been isolated are succinic monoureide, hydantoinacrylic acid, and a-ketoglutaric acid amide (269, 270). The authors reached the conclusion that the first step in the reaction sequence was the hydrolytic formation of imidazolonepropionic 

More recently Brown and Kies (S65) reported the formation from histidine and the excretion in the urine of hydantoin- propionic acid, and also its formation by liver extracts of guinea pig and the rat. The substrate for the oxidation was shown very probably to be imidazolone-propionic acid. No oxidation or formation of hydantoinpropionic acid could be demonstrated if the urocanase activity was first destroyed. The L-hydantoin-5-propionic acid was isolated by chromati raphy, and crystallized. Its identity was unequivocally established. 

It is difficult to explain why 1 mole of Os was consumed per mole of hydantoinpropionic acid formed, since the oxidation of the imidazolone ring to the hydantoin ring requires only one atom of oxygen per molecule. Brown and Kies determined that hydantoinpropionic acid was excreted unchanged when administered to experimental animals. This casts doubt on the reported isolation of hydantoinacrylic acid. 

It is reasonable to assume that imidazolonepropionic acid is the substrate for the oxidation to hydantoinpropionic acid, because of its known susceptibility to oxidation. As has been mentioned above, when the oxidation was carried out chemically, no definite products could be detected. This may be because this type of oxidation goes farther than the formation of hydantoin propionate. From the data for the enzymic formation of hydantoinpropionic acid the most reasonable formulation of the reaction is the following Eq. (18.). 

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