Imidazolonepropionic acid

Increased urinary formiminoglutamic acid in the absence of folic acid deficiency or cobalamine C disease is indicative of formiminotransferase deficiency. Accumulation of imidazolonepropionic acid is not observed, but there is an abnormal excretion of its oxidation product, hydantoin-5-pro-pionic acid. Loading tests with histidine will enhance the excretion. Confirmation of the defect is made by enzyme analysis probably the liver is the only suitable tissue. Affected patients were mentally retarded and/or had convulsions however, a number of healthy siblings with the biochemical abnormality have been described. 

Subsequently crystalline formiminoglutamic acid was isolated 251, 252), its composition determined, and its identity proved by synthesis 253, 254). Synthesis was carried out by two different routes and by methods designed to avoid likelihood of cyclization 253, 254). This is because the elementary analysis of formiminoglutamic acid is identical with that of imidazolonepropionic acid, which also is an intermediate in the degradation of urocanic acid. 

Imidazolonepropionic acid ( 264-m/i material ) is unstable in alkali and is very sensitive to light and oxidizing agents. Addition of HjOj or persulfate caused the absorption at 264 m to disappear instantly. No well-defined products of the oxidation could be detected. 

Brown and Kies determined that imidazolonepropionic acid has an acid group of pK 4.4. 

When a crude liver extract is added to the purified urocanase, decomposition of urocanic acid proceeds to W-formimino-L-glutamic acid. The enzyme carrying out this stage of the reaction has been named imidazolonepropionic acid hydrolase. In view of the fact that im-idazolonepropionic acid has not been isolated and study of the hydrolysis reaction can only be performed in incubation mixtures in which urocanic acid is reacted with purified urocanase very little is known about the properties of the hydrolase enzyme. This enzyme has been purified about tenfold by ammonium sulfate fractionation in our laboratory (266). The enzyme activity is shown by an acceleration in the rate of the decomposition of the 264 my absorption. The product formed was shown to be formimino glutamic acid by testing with purified formiminotransferase which is specific for this compound. 

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.). 

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... 

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