Urocanic acid , imidazole ring

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-... 

The amino acid L-histidine is the assumed building block in the biosynthesis of pilocarpine (27) and other imidazolic alkaloids due to the presence of glyoxaline ring [8, 23]. First attempts to clarify this pathway were proposed by Boit and Leete that considered the phosphate derivative of 2-oxo-3-(5-imidazofyl)-propanol, also known as imidazole pyruvic acid, as imidazole ring precursor (Scheme 25.1-Pathway 1) [8]. This initial biosynthesis proposal was improved detailing the lactone ring formation by aldol condensation. Another biosynthetic approach suggested condensation of 2-oxobutyric acid (lactone moiety) with urocanic acid (imidazole moiety) (Scheme 25.1- Pathway 2) [8, 39]. 

Solid phase attachment of histidine-containing peptides by anchoring the imidazole ring to trityl resins has been developed for combinatorial library preparation of diketopiperazines <99TL809>. Histidine, histamine, and urocanic acid are edl imidazole-containing molecules that have been attached to a trityl-type resin to allow their application to combinatorial chemistry <99TL2825>. 

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. 

Edlbacher and co-workers - concluded that urocanic acid formation represented a minor pathway in the metabolism of histidine. It was their contention that histidase directly caused the opening of the imidazole ring of histidine to yield the compound with the properties mentioned above. Indirect support for this claim was provided by the observation that urocanic acid, when administered to rabbits, was not easily metabolized, and upon injection into guinea pigs was excreted in the urine practically quantitatively. ... 

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... 

The correct metabolic pathway to glutamic acid and proof that urocanic acid was an intermediate in the reaction sequence was obtained by em ploying preparations of histidine labeled with N in the a-position of the side chun and N-1, or with C at C-2 of the imidazole ring (see Fig. 

The enzyme which deaminates histidine to form urocanic acid has been called histidase, desaminohistidase, histidine deaminase, histidine-aenzyme preparation which degraded histidine to a product in which the imidazole ring had been split. This process is now known to consist of several steps. The name histidase was adopted by Mehler and Tabor 248) for the enzyme which converts histidine to urocanic acid and ammonia. Histidine deaminase, as a name, has the advantage of identifying the nature of the reaction. 

The receptor ligand transferrin has been incorporated into chitosan/DNA polyplexes which enhanced gene transfer up to four-fold compared to immod-ified chitosan [67]. In a similar fashion, incorporation of C-terminal domain of adenovirus fiber knob protein enhanced transfection up to 130-fold in HeLa cells. Further modifications include the incorporation of hydrophobic moieties to generate dodecylated chitosan, deoxychoHc acid modified chitosan. Urocanic acid-modified chitosan [68] was reported to mediate efficient gene delivery it was hypothesized that the imidazole ring plays a crucial role for enhancing the release of internalized polyplexes from endosomal vesicles. 

Urocanic acid (UA) bearing an imidazole ring [59] was introduced to chitosan. The transfection efficiency increased with increasing substitution value of UA... 

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