Amine pyruvate aminotransferase

Shin and Kim [39] used the accessible surface area of essential amino acid residues of the amine pyruvate aminotransferase and various amino donors and acceptors to explore the active site structure. Their results suggested a model consisting of two pockets, one large and the other small. The size difference between the binding pockets and the strong repulsion for a carboxylate in the small pocket were key determinants of the substrate specificity and stereoselectivity. 

Shin J., Kim B., Exploring the Active Site of Amine Pyruvate Aminotransferase on the Basis of the Substrate Structure-Reactivity Relationship How the Enzyme Controls Substrate Specificity and Stereoselectivity,/. Org. Chem. 2002, 67, 2848-2853. 

In the other, the amino acid is rotated 180° so that the a-hydrogen protrudes behind the plane of the paper. Dunathan studied pyridoxamine pyruvate aminotransferase, an enzyme closely related to PLP-requiring aminotransferases and which catalyzes the transamination of pyridoxal with L-alanine to form pyridox-amine and pyruvate. The same reaction is catalyzed by the apoenzyme of aspartate aminotransferase. In both cases, when the alanine contained 2H in the a position the 2H was transferred stereospecifically into... 

An associated cascade process that combines a thiamine diphosphate (ThDP)-dependent ligase with enantiocomplementary m-TAs was described recently to access norephedrine (NE) and norpseudoephedrine (NPE) in only two steps from cheap starting materials [52]. The system uses the acetohydroxyacid synthase I (AHAS-I) from E. coli to yield (P)-phenylacetylcarbinol [(R)-PAC, 98% ee] via carboligation with benzaldehyde, which was then directly converted to the desired ephedrine derivatives (NE or NPE) by the appropriate choice of m-TA (Scheme 4.15). Moreover, a novel cascade was introduced with this system ( recycling cascade ) because the coproduct of the reductive amination (pyruvate) could be elegantly removed/recycled without addition of further catalyst, increasing thereby the intrinsic overall efficiency. Several aminotransferases were tested initially for the reductive amination because the benzaldehyde also serves as a suitable substrate for... 

The investigation of the aminotransferase activity of apple ACS carried out by Feng et al reveals that it is able to reductively aminate PLP to PMP by transamination of some L-amino acids to their corresponding a-keto acids. The enzyme has shown substrate specificity with the preference of Ala > Arg > Phe > Asp. The addition of excess pyruvate causes a conversion of the PMP form of the enzyme back to the PLP form. The quite unstable PMP form of ACS can generate apoenzyme, which captures PLP to restore its physiologically active form. 

Reaction (20.12) is catalyzed by glutamate-pyruvate transaminase (GPT), also known as alanine aminotransferase, and Equation (20.13) is catalyzed by glutamate dehydrogenase. Note that these reactions are completely reversible. The reverse of deamination, for example, if one wanted to synthesize alanine from ammonia and pyruvate, is amination. 

EXAMPLE 13.14 Amino acids taken up from the blood by the liver are deaminated by a class of enzymes called transaminases or aminotransferases. These enzymes catalyze the conversion of the carbon atom containing the amine (—NH2) group to a ketone (2-oxoacid), and in the process a 2-oxoacid is converted to an amino acid. The commonly prodnced 2-oxoacids are pyruvate, oxaloacetate, and 2-oxoglutarate. (Transamination reactions are discussed more fully in Sec. 14.1.)... 

Amination of aldehydes by an amino acid aldehyde aminotransferase from Mercurialis perennis was inhibited strongly by pyruvate, oxaloacetate, and oxoglutarate, and this inhibition was suspected to be competitive (Hartmann et al., 1972). Formation of coniceine by an alanine 5-keto-octanal aminotransferase was inhibited competitively by pyruvate and uncompetitively by glyoxylate (Roberts, 1978). With the L-ornithine 2-oxoacid aminotransferase from Cucurbita pepo, severe inhibition by valine, leucine, and isoleucine could be observed, but there was no inhibition by lysine or proline (Lu and Mazelis, 1975). Cucurbita maxima ornithine aminotransferase, however, was reported to be inhibited by proline (Splittstoesser and Fowden, 1973), as well as by canavanine and diaminobutyrate. 

Hohne, M., Kuhl, S., Robins, K., and Bornscheuer, U. (2008) Efficient asymmetric synthesis of chiral amines by combining aminotransferase and pyruvate decarboxylase. ChemBioChem, 9, 363-365. 

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