Broad substrate selectivity

Segawa H, Fukasawa Y, Miyamoto K, Takeda E, Endou H, Kanai Y. Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity. J Biol Chem 1999 274 19745-19751. 

Hydrolases catalyze the hydrolytic cleavage of C-0, C-N, C-C, and some other bonds including phosphoric anhydride bonds. They possess several attractive features, such as broad substrate selectivity and high stereospecificity. This has made them a popular choice for the conduction of many biotransformafions as well as a powerful addition to the organic chemistry toolbox. Hydrolases also often catalyze several related reactions, such as condensations and alcoholysis. 

In addition to the preceding complexities, the P450 enzymes have some unique characteristics that complicate the design of experimental protocols. Because of the broad substrate selectivities for these enzymes, the enzymes are not optimized for the metabolism of a particular substrate. Therefore, the reaction conditions (i.e., pH, ionic strength, temperature) that result in optimum velocities for a given reaction are dependent on both the enzyme and the substrate. To further complicate matters, the velocities for these enzymes tend to vary greatly with changes in these reaction conditions. This variation may well be due to the dependence of the reaction velocity on several pathways in the catalytic cycle. 

As one would expect on the basis of their specificity panel for naturally occurring nucleosides, hENTl and hENT2 show broad substrate selectivity and, when available, with apparent JQi values lower than those reported for CNTs. Moreover, gemcitabine and other nucleoside analogues used in the treatment of lymphoid malignancies also appear to be better substrates for hENTl than for hENT2 [87]. 

The three steps of methylation of norlaudanosoline (iii, iv, v) are catalyzed by three kinds of methyltransferases (60MT, CNMT, and 4 OMT). These enzymes need 5-adenosyl-L-methionine (SAM) as the methyl donor. The 60MT and CNMT from C. japonica have broad substrate selectivity. Therefore, 60MT can catalyze the 6-(9-methlyation of not only norcoclaurine (VI) but also norlaudanosoline (iii). Similarly, CNMT can catalyze the N-methylation of not only coclaurine (VII) but also 6-(9-methylnorlaudanosoline (iv). 

---