B-Transamination

The anaerobic metabolism of L-phenylalanine by Thauera aromatica under denitrifying conditions involves several steps that result in the formation of benzoyl-CoA (a) conversion to the CoA-ester by a ligase, (b) transamination to phenylacetyl-CoA, (c) a-oxidation to phenylglyoxalate, and (d) decarboxylation to benzoyl-CoA (Schneider et al. 1997). 

Deamination removal of the amino group (-NH ) from a chemical compound (usually an amino acid). MetaboUcally, D. may occur by a) oxidative D. of amino acids to ketoacids and ammonia by Flavin enzymes (see) and pyridine nucleotide enzymes (see Amino acids, Table 3) b) Transamination (see) in which an amino group is transferred fiom an amino to a keto compound, and c) removal of ammonia from a compound, leaving a double bond, e.g. the D. of L-aspartate to marate, and the D. of histidine to urocanic acid. IVansamination is important in the synthesis of amino acids from tricarboxylic acid cycle intermediates the reverse reactions feed excess amino acids into the tricarboxylic acid cycle for oxidation. 

Deamination, Transamination. Two kiads of deamination that have been observed are hydrolytic, eg, the conversion of L-tyrosiae to 4-hydroxyphenyUactic acid ia 90% yield (86), and oxidative (12,87,88), eg, isoguanine to xanthine and formycia A to formycia B. Transaminases have been developed as biocatalysts for the synthetic production of chiral amines and the resolution of racemic amines (89). The reaction possibiUties are illustrated for the stereospecific synthesis of (T)-a-phenylethylamine [98-84-0] (ee of 99%) (40) from (41) by an (5)-aminotransferase or by the resolution of the racemic amine (42) by an (R)-aminotransferase. 

Fig. 3. (a) Reaction of pytidoxal 5 -phosphate (PLP) witii an amino-temiinal amino group of hemoglobin (Hb). The reagent is in the form of a Schiff s base with tris(hydroxymethyl)aminomethane [77-86-1] (Tris) buffet, and the reaction is a transamination, (b) The resulting unstable Schiff s base is reduced with... 

Fig. 25.8 (a) Normal metabolism, in which phenylalanine is converted by phenylalanine 4-mono-oxygenase to tyrosine, (b) Phenylketonuria, in which there is a transamination reaction between phenylalanine and a-ketoglutaric acid. Phenylalanine 4-mono-oxygenase is absent in about 1 in every 10000 human beings because of a recessive mutant gene. 

The third method that we have used to prepare these diazaboracyclohexane systems is the transamination reaction of 1,3-diaminopropane with the bis(dimethyiamino)boryl compound 8 (eq 8). The solid products 12 and 13, which contain, respectively, two or three of the BN2C3 heterocycles linked by B-N bonds, could not be distilled (or crystallized), but they were thermally stable to at least 200°C. After minor impurities were removed from 12 by vacuum distillation and from 13 by washing with hexane, the structures were confirmed by1H, 13C, and 11B NMR spectroscopy. 

Vitamin Ba (pyridoxine, pyridoxal, pyridoxamine) like nicotinic acid is a pyridine derivative. Its phosphorylated form is the coenzyme in enzymes that decarboxylate amino acids, e.g., tyrosine, arginine, glycine, glutamic acid, and dihydroxyphenylalanine. Vitamin B participates as coenzyme in various transaminations. It also functions in the conversion of tryptophan to nicotinic acid and amide. It is generally concerned with protein metabolism, e.g., the vitamin B8 requirement is increased in rats during increased protein intake. Vitamin B6 is also involved in the formation of unsaturated fatty acids. 

Figures 6.2a and b illustrate important examples of transamination reactions.

Several characterized NRPSs utilize alternative methods for chain termination. In some synthetases, the TE domain of the final module is replaced by an NAD(P)H-dependent reductase domain. Reduction of a peptidyl-S-PCP substrate through a two-electron reaction leads to the formation of a transient aldehyde, which is subsequently converted into a cyclic imine or hemiaminal through intramolecular cyclization. This two-electron reaction is utilized in the biosynthesis of nostocyclopeptides, the saframycins, ° and anthramycin. Alternatively, a four-electron reduction to the primary alcohol is observed in the biosynthesis of mycobacterial peptidolipids, linear gramicidin," " the myxalamides, lyngbyatoxin, " and myxochelin A 75,76 alternative four-electron reduction pathway involving aldehyde formation, transamination, and reduction to a primary amine occurs in the biosynthesis of myxochelin B. ... 

Breaking of bond b accounts for PLP-dependent decarboxylations. Decarboxylation of the intermediate aldimine is facilitated in the same way as loss of a proton in the transamination sequence. The pro-tonated nitrogen acts as an electron sink, and the conjugated system allows loss of the carboxyl proton. 

Among the NH2 transfer reactions, transaminations (1) are particularly important. They are catalyzed by transaminases, and occur in both catabolic and anabolic amino acid metabolism. During transamination, the amino group of an amino acid (amino acid 1) is transferred to a 2-oxoacid (oxoacid 2). From the amino acid, this produces a 2-oxo-acid (a), while from the original oxoacid, an amino acid is formed (b). The NH2 group is temporarily taken over by enzyme-bound pyridoxal phosphate (PLP see p. 106), which thus becomes pyridoxamine phosphate. 

During the degradation of most amino acids, the a-amino group is initially removed by transamination or deamination. Various mechanisms are available for this, and these are discussed in greater detail in B. The carbon skeletons that are left over after deamination undergo further degradation in various ways. 

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