Amino add decarboxylase

ATP, Determination of Firefly Luminescence (Strehler and Totter) Bacterial Amino Add Decarboxylases in Determination of Amino... 

Mammalian Amino Add Decarboxylases. Amino acid decarboxylases occur in many animal tissues. Histidine decarboxylase of kidney has a pH optimum near 9. The decarboxylation product, histamine, has very powerful pharmacological effects in animals, and its formation in minute quantities has been measured pharmacologically. This nonspecific type of assay has also been used to detect histidine decarboxylase in other tissues. More specific assays have recently shown this enzyme to occur in mast cells, in which histamine accumulates the stored histamine is released by rupture of these fragile cells. 

Amino Adds, Determinalion by Use of Bacterial Amino Add Decarboxylases (Gale). IV 285... 

L-aromatic amino add decarboxylase (EC 4.1.1.26) is a stereospedfic enzyme for several l-aromatic amino acids (phenylalanine, tyrosine, DOPA. S-HTP). It is widely distributed and is characterized by its pyridoxal-S -phosphate requirement as coenzyme. The general r61e of this enzyme in the biogenesis of many amines is well documented but its regulatory action seems doubtful in view of its large excess compared with the low levels of tryptophan-S-hydroxylase and tyrosine hydroxylase. Numerous substances belonging to various chemical classes inhibit this enzyme in vivo and have been reviewed in Section B. Chapter 5.2 and elsewhere... 

Decarboxylase Decarboxylation of amino adds and simple phenolic adds, primarily p-hydroxylated L-dopa, tyrosine... 

Decarboxylation (Group b). Tire bond to the carboxyl group of an amino add substrate is broken in reactions catalyzed by amino acid decarboxylases.191192... 

Note that the p/C, of a residue at the active site can vary substantially from the value observed for the free amino add in water [27]. For example, the active site of the enzyme acetoacetate decarboxylase features a lysine residue with a very low p/C, of 5.9 (cf. pJCa 9 for the free amino add). In this case, the pICa is influenced by an adjacent protonated lysine residue (Figure 5.6) [28,29]. A similar redudion, though less dramatic, is observed for aliphatic diamines (e.g., the two p/C, values for 1,4-diaminobutane are 10.80 and 9.35, respectively). 

Bacterial Amino Acid Decarboxylases in Determination of Amino Adds (Gale). 4... 

Allenic amino add derivatives SO, which are of spedal interest as selective vitamin Bs decarboxylase inhibitors [35], are accessible fbrough 1,6-cuprate addition to 2-amino-substituted enynes 49 (Eq. 4.22) [36]. Because of the low reactivity of these Michael acceptors, however, the reaction succeeds only with the most reactive cuprate the t-butyl cyano-Gilman reagent tBu2CuLi-LiCN. Neverthdess, the addition products are obtained with good chemical yields, and selective deprotection of dther the ester or the amino functionality under addic conditions provides the desired tai et molecules. 

The synthesis of serotonin from tryptophan is carried out in two steps controlled by two enzymes tryptophan hydroxylase (TPH) and aromatic L-amino acid decarboxylase (AADC). The second enzyme, A ADC, is also known as DOPA carboxylase or 5-hydroxytryptophan carboxylase when it acts specifically in 5-HT synthesis. In the first step, the TPH adds a hydroxyl chemical group (OH) to tryptophan to make 5-hydroxytryptophan, Fig (1). In the second step, AADC removes the carboxyl group (-COOH) from 5-hydroxy tryptophan to make serotonin. Fig (2). 

DA is involved in movement disorders, as well as in schizophrenia and substance abuse. The neurotransmitter is synthesized from a precursor amino add tyrosine. L-tyrosine is hydroxylated to L-dopa by the action of the enzyme, tyrosine hydroxylase. L-dopa is then converted to DA by the L-aromatic amino acid enzyme decarboxylase. 

Several amino add a-decarboxylases of bacterial origin are known that do not... 

Rassin D K., Sturman J A, and Gaull G E, (1981) Sulfur ammo acid metabolism m the developing rhesus monkey brain. Subcellular studies of taurine, cysteinesulfmic acid decarboxylase, 7-amino-butyric acid, and glutamic add decarboxylase, / Neurochem 37, 740-748... 

In Scheme 13.40 and as noted above, the action of the iron-containing enzyme tyrosine 3-monooxygenase (EC 1.14.16.2) is shown to effect the conversion of tyrosine (Tyr, Y) and oxygen (O2) to 3,4-dihydroxyphenylalanine (L-dopa), while the cofactor tetrahydrobiopterin undergoes oxidation to 4a-hydroxytetrahydrobiop-terin. Then, the general aromatic-L-amino acid decarboxylase (EC 4.1.1.28), an enzyme that uses pyridoxal as a cofactor, effects the decarboxylation of the bisphe-noUc add to the corresponding amine, dopamine [3,4-dihydroxyphenethylamine, 2-(3,4-dihydroxyphenyl)ethanamine]. 

V. MECHANISMS FOR THE BREAKDOWN OF AMINO ACIDS A. General Mechanisms (a) Decarboxylation of Amino Acids In the presence of decarboxylases amino adds give CO, and an amine according to the general reaction ... 

The carboxylases have for their coenzyme pyridoxal phosphate which acts according to the mechanism described on p. 174. A whole series of decarboxylases exists, each being specific for the L-form of a given amino add. Certain of them have been isolated from animal tissues such as liver and kidney, but the majority have been isolated from micro-organisms in which the enzymes appear if their specific substrate is present in the culture medium. In micro-organisms therefore these decarboxylases are adaptive enzymes. The amines produced by the decarboxylation of amino acids (Table XIII) often possess pharmacological activity this is the case for histamine, the product of the decarboxylation of histidine. 

Amino add (aromatic) decarboxylase inhilntion - in vivo (Cell culture, cells-PC-12) at 10.0 nM. 178... 

Biogenic amines are formed from amino acids by the action of carboxy-lyases (decarboxylases containing as a cofactor pyridoxal 5 -phosphate), or arise from amino adds and carbonyl compounds by the action of transaminases (see Section 8.2.10.1.2). The so-called endogenous biogenic amines are the products of metabohsm and at low concentrations are natural components of almost aU foods. Exogenous biogenic amines are formed in foods as a result of microbial contamination and fermentation processes. 

Due to the absence of a hydrogen atom on the a-carbon, the a-fluoroalkyl amino acids (except, of course, the fluoroalanines, vide supra) cannot undergo an elimination of HR Consequently, they are more stable than fluoroalanines and other jS-fluoro amino acids previously described. On the other hand, similar to proteogenic amino acids, jS-fluoro amino acids and a-fluoroalkyl amino acids are generally substrates of pyridoxal phosphate depending on enzymes such as racemases and decarboxylases. When an amino acid is a substrate of such enzymes, the enzyme induces the development of a negative charge on the a-carbon, which can initiate a /(-elimination process. This reaction affords an electrophilic species (Michael acceptor type), which is able to add a nucleophilic residue of the enzyme. This notion of mechanism-based inhibitor is detailed in Chapter 7. 

Branched-Chain Oxo-acid Decarboxylase and Maple Syrup Urine Disease The third oxo-add dehydrogenase catalyzes the oxidative decarboxylation of the branched-chain oxo-acids that arise from the transamination of the branched-chain amino acids, leucine, isoleuctne, emd vtdine. It has a similEU subunit composition to pyruvate and 2-oxoglutarate dehydrogenases, and the E3 subunit (dihydrolipoyl dehydrogenase) is the stune protein as in the other two multienzyme complexes. Genetic lack of this enzyme causes maple syrup urine disease, so-called because the bremched-chain oxo-acids that are excreted in the urine have a smell reminiscent of maple syrup. 

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