Hydrolases amidohydrolase

Hydrolases Amidohydrolases Esterases Urease Acetylcholine esterase Hydrolysis reactions Urea Acetylcholine NH3, CO2 or H+ H +... 

Once inside the cell, anandamide is hydrolyzed by a specific hydrolase, anandamide amidase (AEAase) or fatty acid amidohydrolase (FAAH) (Desarnaud, 1995 Deutsch, 1993). This enzyme is membrane associated and shows significant specificity for anandamide (Desarnaud, 1995 Lang, 1999). 

This enzyme [EC 3.5.1.10], also known as formyltetrahydrofolate amidohydrolase and formyl-FH4 hydrolase, catalyzes the hydrolysis of 10-formyltetrahydrofolate to yield formate and tetrahydrofolate. 

Penicillin and related antibiotics are inactivated by P-lactamases (Box 20-G), some of which resemble serine proteases in forming acyl enzymes with active site serine side chains.656 657 Others are zinc metallogen-zymes.658/659 Amidohydrolases such as asparaginase and glutaminase,660/661 deacetylases,662 and many other hydrolases can also be described as acyltransferases. 

The title retains the trivial name for enzymes with the systematic name of urea amidohydrolase and the Enzyme Commission code number of EC 3.5.1.5. Ureases are hydrolases acting on C-N bonds (nonpeptide) in linear amides and thus belong to a group that includes glutaminase, form-amidase, and formyltetrahydrofolate deformylase. The title is plural to emphasize that urease activity may be exhibited by several protein species. Urease, singular, has come to mean by common usage, that particular enzymic protein first crystallized by Sumner from jack bean... 

Several other proteins show a low, but significant amino acid identity with atzA (Table 22.4). All of these, urease-alpha subunit (urea amidohydrolase), cytosine deaminase, and imidazolone-5-propionate hydrolase, catalyze hydrolytic reactions with substrates involved in the metabolism of nitrogenous compounds (Sadowsky et al 1998). A Rhizobium strain capable of atrazine dechlorination has been isolated from a soil that was previously treated with atrazine (Bouqard et al., 1997). This bacterium could not mineralize atrazine, and it accumulated hydroxyatrazine as the sole metabolite after long-term incubations. Interestingly, 22 of the 24 identified amino acids at the N-terminus of the atrazine halidohydrolase from Rhizobium were identical with atzA from Pseudomonas strain ADP. 

Ueda N, Yamamoto S (2000) Anandamide amidohydrolase (fatty acid amide hydrolase). Prostaglandins Other Lipid Mediat 61 19-28... 

The actual enzymes involved in fatty acid amides (FAAs) metabolism remained unknown until the late 1990s, when a rat liver oleamide hydrolase activity was affinity-purified and its cDNA was cloned (Cravatt et al., 1996). Oleamide amidase was connected to AEA hydrolysis, because AEA and oleamide were catalyzed by the same enzyme, called fatty acid amide hydrolase (FAAH A-arachidonoylethanolamine amidohydrolase, EC 3.5.1.4) (Maurelli et al.,... 

Enzymes that contain binuclear metal centers are also well suited to catalyze hydrolysis reactions, including a number of the reactions described above for the mononuclear metallohydrolases. Additionally, several of the examples that are discussed here belong to the enzyme superfamilies described above, specifically the amidohydrolase, zinc a,/3-hydrolase, and metallo-/31 superfamilies. The substrates for the binuclear metallohydrolases are also biologically diverse, including proteins, peptides, nucleotides, polyamines, and xenobiotics. The binuclear nature of these metal centers produces an active site with altered properties compared to the mononuclear counterparts, and therefore catalysis by these enzymes occurs with alternative reaction mechanisms. Readers are referred to the preceding sections for background information pertaining to enzymes that have already been discussed. 

Anandamide amidohydrolase / Fatty acid amide hydrolase... 

Hydrolases None Lipases Esterases Galactosidases, glucosidases Epoxide hydrolases Peptidases, peptidohydrolase Acylases Amidases, amidohydrolases Nitrilases Hydantoinases... 

The discovery of anandamide (arachidonoyl ethanolamide, AEA) and of its manifold roles in the central nervous system and in the periphery (reviewed in refs. 1 and 2) prompted several researchers to develop analytical methods to assay and characterize the activity of the enzymes responsible for AEA metabolism in various cells and tissues. Fatty acid amide hydrolase (arachidonoyl ethanolamide amidohydrolase, EC 3.5.1.4 FAAH) has emerged as the key AEA hydrolase, showing a molecular mass of approx 64 kDa and an optimum pH of around 9.0 (3). Recently, FAAH has been crystallized,and its three dimensional structure has been determined at 2.8A resolution (4). This enzyme cleaves the amide bond and releases arachidonic acid and ethanolamine. High-performance liquid chromatography (HPLC) is the most widely used method to determine FAAH activity from different sources. We developed a new method (5) based on reversed-phase (RP)-HPLC and on-line scintillation counting, which combines the need for high resolution, reproducibility, and sensitivity... 

Fig. 23.1. Pyrimidine pathways Pathways for the de novo synthesis, interconversion, and breakdown of pyrimidine ribonucleotides, indicating their metabolic importance as the essential precursors of the pyrimidine sugars and, with purines, of DNA and RNA. Note that in contrast to purines salvage takes place at the nucleoside not the base level in human cells and pyrimidine metabolism normally lacks any detectable end-product. The importance of this network is highlighted by the variety of clinical symptoms associated with the possible enzyme defects indicated. 23.10, Uridine monophosphate synthase (UMPS), 23.11a, uridine monophosphate hydrolase 1 (UMPHl), 23.12, thymidine phosphorylase (TP), 23.13, dihydropyrimidine dehydrogenase (DPD), 23.14, dihydropyrimidine amidohydrolase (DHP), 23.15, y -ureidopropionase (UP) (23.11b, UMPH superactivity specific to fibroblasts is not shown). CP, carbamoyl phosphate. The pathological metabolites used as specific markers in differential diagnosis are highlighted...

An alternative mechanism of urea hydrolysis, also involving a two-step reaction sequence, has been demonstrated in yeast, algae and some fungi. Urea is first carboxylated to allophanate by urea carboxylase (urea CO2 ligase, EC 6.3.4.6), a reaction requiring ATP. Allophanate is then hydrolysed by allophanate hydrolase (allophanate amidohydrolase, EC 3.5.1.13) to CO2 and... 

Piotrowski M, Janowitz T, Kneifel H (2003) Plant C-N hydrolases and the identification of a plant Af-carbamoylputrescine amidohydrolase involved in polyamine biosynthesis. J Biol Chem 278 1708-1712... 

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