Enzymatic deamination process

Epivir enzymatic deamination process for the synthesis of (2 / -c s)-2 -deoxy-3-thiacytidine. 

A new development is the industrial production of L-phenylalanine by converting phenylpyruvic add with pyridoxalphosphate-dependent phenylalanine transaminase (see Figure A8.16). The biotransformation step is complicated by an unfavourable equilibrium and the need for an amino-donor (aspartic add). For a complete conversion of phenylpyruvic add, oxaloacetic add (deamination product of aspartic add) is decarboxylated enzymatically or chemically to pyruvic add. The use of immobilised . coli (covalent attachment and entrapment of whole cells with polyazetidine) is preferred in this process (Figure A8.17). 

Tropoelastin molecules are crosslinked in the extracellular space through the action of the copper-dependent amine oxidase, lysyl oxidase. Specific members of the lysyl oxidase-like family of enzymes are implicated in this process (Liu etal, 2004 Noblesse etal, 2004), although their direct roles are yet to be demonstrated enzymatically. Lysyl oxidase catalyzes the oxidative deamination of e-amino groups on lysine residues (Kagan and Sullivan, 1982) within tropoelastin to form the o-aminoadipic-6-semialdehyde, allysine (Kagan and Cai, 1995). The oxidation of lysine residues by lysyl oxidase is the only known posttranslational modification of tropoelastin. Allysine is the reactive precursor to a variety of inter- and intramolecular crosslinks found in elastin. These crosslinks are formed by nonenzymatic, spontaneous condensation of allysine with another allysine or unmodified lysyl residues. Crosslinking is essential for the structural integrity and function of elastin. Various crosslink types include the bifunctional crosslinks allysine-aldol and lysinonorleucine, the trifunctional crosslink merodes-mosine, and the tetrafunctional crosslinks desmosine and isodesmosine (Umeda etal, 2001). 

The liver is responsible for modifying blood protein and Aa composition, which it performs by a series of enzymatic process including transamination, deamination and reamination. The essential aromatic amino acids are degraded in the liver, whereas the branched-chain amino acids are passed to the periphery, where they are metabolised exclusively by skeletal muscle. Non-essential amino acids may be metabolised hepatically or in skeletal muscle. 

The enzymatic process uses water as the solvent and two immobilized enzymes as catalysts at room temperature. In a first step cephalosporin C is deaminated to a-ketoadipyl-7-ACA using a carrier-fixed D-amino acid oxidase in the presence of oxygen. Under reaction conditions the a-keto intermediate is oxidatively decarboxy-lated to glutaryl-7-ACA. In a second step the glutaryl-7-ACA is then hydrolyzed to 7-ACA by a carrier-fixed glutaryl amidase. 

A number of enzymes which participate in the conversion of purine nucleotides to uric acid are known to occur in nature 1-3), and it is clear that four different kinds of enzymatic reactions are required for this overall process dephosphorylation, deamination, cleavage of glycosidic bonds, and oxidation. 

By 1950 biotin had been implicated in a number of seemingly unrelated enzymatic processes, including (1) the decarboxylation of oxaloacetate and succinate (2) the Wood-Werkman reaction , that is, the /5-carboxylation of pyruvate (3) the biosynthesis of aspartate (4) the biosynthesis of unsaturated fatty acids (5) the deamination of certain amino acids (6) the synthesis of certain biotin-independent enzymes. In each case the enzymatic or metabolic basis for these observations can now be explained in terms of the unequivocally established role of biotin as an enzymatic COg carrier or through indirect effects. 

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