Stereochemistry and mechanisms of substitution in phosphates

Stereochemical studies of phosphates are in some respects similar or analogous to studies of saturated carbon, insofar as both are tetrahedral centers and may be achiral, prochiral, or chiral depending upon the identities of the substituent groups. Important differences include a degree of variance in the mechanisms of substitution and their stereochemical consequences as well as many of the methods by which chiral centers are synthesized and analyzed for configuration. 

The other major mechanistic issue addressed in stereochemical work is the 

The true substrates for many enzymes which utilize nucleotides as substrates are metal-nucleotide complexes, often Mg(II)-nucleotides such as Mg-ATP. Numerous 

Concurrently with the development of research dealing with the stereochemical course of substitution at chiral phosphorus centers, the question of the stereospecificities of enzymes for metal-nucleotide complexes has also been addressed. The methodologies developed for the two types of studies differed initially, but significant overlap has appeared. The applications of the two approaches have unmasked the complete stereochemical courses of several phosphotransferase reactions. 

There are two basic prerequisites for completing an enzymatic investigation involving substitution at phosphorus. A substrate for the subject enzyme must first be synthesized with a chirally substituted phosphorus at the reaction center. ATP is a concrete example with three potentially chiral phosphorus centers, each of which undergoes enzymatic substitution. The enzymatic bond cleavages resulting from substitution at P0, and Py are illustrated in Fig. 3. Substitution at Pa is catalyzed by nucleotidyltransferases and certain ATP-dependent synthetases, and substitution at Py is catalyzed by phosphotransferases, other ATP-dependent synthetases and 

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