Amino acid decarboxylases active site

Enzymes that are active in the biosynthesis and processing of hormones are important markers of endocrine cells. Immunoreactivity for aromatic L-amino acid decarboxylase, for example, is widely distributed in neuroendocrine (NE) cells. Tyrosine hydroxylase, dopamine 3-hydroxylase, and phenylethanolamine JV-methyl transferase, in contrast, have a more limited tissue distribution and are confined to known sites of catecholamine biosynthesis. Immunolocalization of these enzymes permits catecholamine-synthesizing abilities to be deduced from paraffin sections. The presence of immunoreactive enzyme, however, does not necessarily imply that the enzyme is present in a functional form. 

Figure 3 compares the proficiencies (kcat/K]v[/kun) of ODCase, several other enzyme decarboxylases [2], and some antibody decarboxylases [3]. The proficiencies of the decarboxylase enzymes, including a variety of amino acid decarboxylases, are nearly equal. Many decarboxylases employ iminium intermediates formed by reaction of an amino acid with a cofactor such as pyruvoyl or pyridoxal, or by reaction of a -keto ester with an active-site lysine residue. These intermediates have been found to be so reactive that the... 

Allenic amino acids belong to the classical suicide substrates for the irreversible mechanism-based inhibition of enzymes [5], Among the different types of allenic substrates used for enzyme inhibition [128, 129], the deactivation of vitamin B6 (pyr-idoxal phosphate)-dependent decarboxylases by a-allenic a-amino acids plays an important role (Scheme 18.45). In analogy with the corresponding activity of other /3,y-unsaturated amino acids [102,130], it is assumed that the allenic amino acid 139 reacts with the decarboxylase 138 to furnish the imine 140, which is transformed into a Michael acceptor of type 141 by decarboxylation or deprotonation. Subsequent attack of a suitable nucleophilic group of the active site then leads to inhibition of the decarboxylase by irreversible formation of the adduct 142 [131,132]. 

Serine hydroxymethyl transferase catalyzes the decarboxylation reaction of a-amino-a-methylmalonic acid to give (J )-a-aminopropionic acid with retention of configuration [1]. The reaction of methylmalonyl-CoA catalyzed by malonyl-coenzyme A decarboxylase also proceeds with perfect retention of configuration, but the notation of the absolute configuration is reversed in accordance with the CIP-priority rule [2]. Of course, water is a good proton source and, if it comes in contact with these reactants, the product of decarboxylation should be a one-to-one mixture of the two enantiomers. Thus, the stereoselectivity of the reaction indicates that the reaction environment is highly hydro-phobic, so that no free water molecule attacks the intermediate. Even if some water molecules are present in the active site of the enzyme, they are entirely under the control of the enzyme. If this type of reaction can be realized using synthetic substrates, a new method will be developed for the preparation of optically active carboxylic acids that have a chiral center at the a-position. 

Amino Acid Systems Glutamine binding sites, 46, 414 labeling of the active site of r-aspartate /3-decarboxylase with yS-chloro-r-ala-nine, 46, 427 active site of r-asparaginase reaction with diazo-4-oxonorvaline, 46, 432 labeling of serum prealbumin with N-bro-moacetyl-L-thyroxine, 46, 435 a pyridoxamine phosphate derivative, 46, 441. 

Other examples of electrophilic metal catalysis are given under section 2.3.3.1. Electrophilic reactions are also carried out by enzymes which have an a-keto acid (pyruvic acid or a-keto butyric acid) at the transforming locus of the active site. One example of such an enzyme is histidine decarboxylase in which the N-terminal amino acid residue is bound to pyruvate. Histidine decarboxylation is initiated by the formation of a Schiff base by the reaction mechanism in Fig. 2.20. 

Effects of 3- and i4.-mercapto-2-amino acids. It has long been known that 1,2- and 1,3-aminothiols, and especially the substrate-like mercapto-amino acids - penicillamine, homocysteine et al. - strongly inhibit many PLP-enzymes(transaminases, c<-decarboxylases, y cystathionase, and others) by condensing with the carbonyl group of PLP in the active site to stable heterocyclic compounds (thiazolidines, resp., thiazanes), see Pefs. 5 ... 

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