Urocanase

Kaminskas E, Y Kimhi, B Maganasik (1970) Urocanase and V-formrmino-L-glutamate formrminohy-drolase of Bacillus subtilis, two enzymes of the histidine degradation pathway. J Biol Chem 245 3536-3544. 

Keul V, F Kaeppeli, C Ghosh, T Krebs, JA Robinson, J Retey (1979) Identification of the prosthetic group of urocanase. J Biol Chem 254 843-851. 

Urocanic acid (2-propanoic acid 3-[lH-imidazol-4-yl] is located superficially in the stratum comeum. Metabolism of epidermal UCA does not occur in situ due to the absence of urocanase, resulting in the accumulation of UCA in the epidermis. Upon UV exposure, naturally occurring trans-UCA converts to the d.s-isomer, in a dose dependent manner, until the photostationary state is reached, when equal quantities of trans- and m-UCA are found in the skin.15 Based on an analysis of the action spectrum for UV-induced immune suppression, and the fact that no immune suppression was observed in mice whose stratum comeum was previously removed by tape stripping, De Fabo and Noonan suggested that urocanic acid was the photoreceptor for UV-induced immune suppression.16 Since the initial experiments many others have documented, the ability of ris-UCA to initiate immune suppression, documented its presence in the serum of UV-irradiated mice, and demonstrated that m-UCA plays a role in UV-induced skin cancer induction. (For a more complete review of the role of m-UCA in immune suppression see two excellent reviews by Norval and colleagues.1718)... 

Bound NAD+ is also present in S-adenosylhomo-cysteine hydrolase,119 120 which catalyzes the irreversible reaction of Eq. 15-14. Transient oxidation at the 3 position of the ribose ring facilitates the reaction. The reader can doubtless deduce the function that has been established for the bound NAD+ in this enzyme. However, the role of NAD in the urocanase reaction (Eq. 15-15) is puzzling. This reaction, which is the second step in the catabolism of histidine, following Eq. 14-44, appears simple. However, there is no obvious... 

Uridylate kinase 655 5 -Uridylic acid. See UMP Urocanase reaction 778 Urocanic acid 755,756s Urokinase 634 Uronic acid 164 Uroporphyrin(s) 843 Uroporphyrin I, 845s Urothione 804s, 891 Urticaria 385 Usher protein 364... 

Changes in glucose-6-phosphatase, forminoglutamic acid transferase, urocanase, formylase, methyl-H4-folate dehydrogenase, histidiase, glutamic oxalacetic transaminase and carbonyl transferase and ornithine... 

Figure 10.6. Catabolism of histidine - basis of the FIGLU test for folate status. Histidase, EC 4.3.1.3 urocanase, EC 4.2.1.49 FIGLU formiminotransferase, EC 2.1.2.5. THF, tetrahydrofolate.

Urocanic acid (imidazole acrylic acid) is converted to the imidazole propionic acid in the presence of uro-canase by oxidation of the ring carbon and reduction of the side chain (see Fig. 3-23). Urocanase has been found in the liver of mammals its acivity varies considerably, depending upon the species. Urocanase has been purified extensively from beef liver [95]. The pro-... 

Rao, D.R., Greenberg, D.M. Studies on the enzymic decomposition of urocanic acid. II. Properties of products of urocanase reaction. Biochim. biophys. Acta (Amst.) 43, 404-418 (1960)... 

Urocanic acid is degraded by urocanase. Although this enzyme has been purified from both animal and bacterial sources,its mode of action remains obscure. The first product to accumulate is the open-chain formiminoglutamic acid. There is no evidence for more than one enzyme participating in this reaction which involves the addition of two water molecules and opening the imidazole ring (IV). No dissociable cofactor has been detected. The enzyme that removes the 277 mp absorption has a pH optimum near 7. 

The hydrolytic sphtting of urocanic acid by liver extracts was first observed by Sera and Yada, and confirmed by others. " The enzyme that causes this decomposition was named urocanase. 

The principal objection of Edlbacher and co-workers to the hypothesis that histidine was catabolized by the way of urocanic acid was that their purified histidase preparations split the imidazole ring of histidine in the absence of urocanase and did not act on urocanic acid. Histidase prepared according to the best purification procedure from Edlbacher s laboratory by Mehler and Tabor yielded a product which had an eightfold increase in the ability to produce urocanic acid from histidine but did not split the imidazole ring. This preparation did not attack... 

Properties. Histidase and urocanase were separated from each other by Takeuchi by taking advantage of the observation that heating liver extract at 55°C. for 30 minutes and then acidifying the solution caused the histidase to be thrown down in the voluminous precipitate formed, while the urocanase remained in the supernatant liquid. 

Edlbacher and Viollier found that the two enzymes could be separated owing to the fact that histidase is selectively absorbed on Pbs(P04)2 and urocanase on Cas(P04). 

In Pseudomonas fluorescens extract, histidase free from urocanase can be prepared by heating the extract at 85°C. for 15 minutes. By this procedure all ability to destroy urocanic acid is lost, but the full capacity to deaminate histidine is retained when the product is supplemented with 10 M glutathione. 

Some of the reported purifications of histidase can not be judged for their freedom from urocanase, because, apparently, this was not determined. The test method employed was merely the rate of liberation of NHa from histidine. 

Histidase activity can be measured by determining the accumulation of urocanic acid, through its strong ultraviolet absorption. The optimum activity of histidase is at pH 7.8 of urocanase, at pH 7-8. ... 

Urocanase deficiency is a very rare autosomal recessive disorder that may be benign in most affected individuals. The reported cases with the disorder are less than ten. The enzyme defect is urocanase, an enzyme normally expressed in liver. The block in conversion of urocanic acid to imida-... 

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