Substrates Glycine

Wu, C.S. Neely, W.C. Worley, S.D. A Semiempirical Theoretical Study of the Molecular Interaction of Cocaine with the Biological Substrate Glycine. 7 Comput. Chem. 12 862-867, 1991. 

Of the known classes of aldolase, DERA (statin side chain) and pyruvate aldolases (sialic acids) have been shown to be of particular value in API production as they use readily accessible substrates. Glycine-dependent aldolases are another valuable class that allow access to p-hydroxy amino acid derivatives. In contrast, dihydroxy acetone phosphate (DHAP) aldolases, which also access two stereogenic centres simultaneously,... 

How would substrate preference be changed if the glycine residues in trypsin at positions 216 and 226 were changed to alanine rather than to the more bulky valine and threonine groups that are present in elastase This question was addressed by the groups of Charles Cralk, William Rutter, and Robert Fletterick in San Francisco, who have made and studied three such trypsin mutants one in which Ala is substituted for Gly at 216, one in which the same substitution is made at Gly 226, and a third containing both substitutions. 

Substrate specificity is determined by high affinity for the cognate neurotransmitter substrate. However, low affinity uptake does also have a part in the clearance of transmitters from the interstitial space (e.g., in uptake mediated by the extraneuronal monoamine transporter, EMT) and in the intestinal absoiption of glycine and glutamate. It is obvious that there is an evolutionary relation of neurotransmitter transporters and amino acid and cation transporters in epithelia. 

Optimum pH was determined by following the decrease in viscosity of the reaction mixture using 0.187 % pectin as a substrate in 0.05 M tris-HCl buffer (pH 7.0-9.0) or glycine buffer (pH 9-10). Controls were run without enzyme preparation. 

Aminopeptidase A is another brush border membrane enzyme which has been the subject of various studies [79,81,83-86], It has been found in the intestinal brush border membrane of humans, rabbits, rats, and pigs and is active against peptides with acidic amino acids at the amino terminus. Its activity against dipeptides is more limited. Shoaf et al., isolated three rat brush border aminopeptidases with distinct but somewhat overlapping substrate specificities. These enzymes had preference for dipeptides containing methionine, arginine, or aspartic acid and glycine. The optimal pH for activity of aminopeptidase was reported to be 7-8. 

Lopez-Corcuera, B., Nunez, E., Martinez-Maza, R Geerlings, A., and Aragon, C. (2001) Substrate-induced conformational changes of extracellular loop 1 in the glycine transporter GLYT2. J. Biol. Chem. 276,43463-13470. 

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