Acid phosphatase transphosphorylation

Phosphates of pharmaceutical interest are often monoesters (Sect. 9.3), and the enzymes that are able to hydrolyze them include alkaline and acid phosphatases. Alkaline phosphatase (alkaline phosphomonoesterase, EC 3.1.3.1) is a nonspecific esterase of phosphoric monoesters with an optimal pH for catalysis of ca. 8 [140], In the presence of a phosphate acceptor such as 2-aminoethanol, the enzyme also catalyzes a transphosphorylation reaction involving transfer of the phosphoryl group to the alcohol. Alkaline phosphatase is bound extracellularly to membranes and is widely distributed, in particular in the pancreas, liver, bile, placenta, and osteoplasts. Its specific functions in mammals remain poorly understood, but it seems to play an important role in modulation by osteoplasts of bone mineralization. 

Acid phosphatase (acid phosphomonoesterase, EC 3.1.3.2) also catalyzes the hydrolysis of phosphoric acid monoesters but with an acidic pH optimum. It has broad specificity and catalyzes transphosphorylations. Acid phosphatases are a quite heterogeneous group with monomeric, dimeric, larger glycoprotein, and membrane-bound forms. Acid phosphatase activity is present in the heart, liver, bone, prostate, and seminal fluid. Prostate carcinomas produce large quantities of acid phosphatase, and the enzyme is, therefore, used as a biomarker [141]. 

Acid phosphatase or orthophosphoric monoester phosphohydrolase (EC 3.1 3.2) activity is widespread throughout nature. Hydrolysis of a variety of orthophosphate esters as well as transphosphorylation reactions are catalyzed by enzymes from many sources. Table I illustrates their ubiquitous nature. 

Vescia and Chance Hi) demonstrated that fluoride and tartrate inhibition vide infra) of acid phosphatase showed completely different kinetics when the hydrolysis of phenyl phosphate was compared with transphosphorylation from this substrate to glucose. Figures 5 and 6 (41) show that fluoride inhibition is competitive when the data are plotted according to Lineweaver and Burk. However, the inhibition is noncompetitive with respect to transphosphorylation of the same substrate to glucose. The authors suggested that there are two distinct sites... 

In general, the addition of aliphatic alcohols to the reaction media may enhance the activity of acid phosphatases by acting as phosphate acceptors in a transphosphorylation reaction [46],... 

Because phytase, an inexpensive acid phosphatase, is only active at lotv pH but virtually inactive at pH 7.5 in tvhich aldolases have their catalytic optimum, this enables the independent staging of a one-pot synthetic cascade betvireen (1) transphosphorylation, (2) aldolization, and (3) product dephosphorylation simply by stvitching the pH [178]. 

These enzymes differ from APs in the absence of metal ions. The bovine liver enzyme was used to carry out the transphosphorylation from phenyl (i )-[ 0, 0, 0] phosphate to (6)-propane-l,2-diol, and demonstrated that the reaction proceeds with net retention of stereochemistry. This indicates that the catalytic reaction proceeds via formation of an intermediate, with two inversions of configuration at phosphorus. The nucleophilic residue was identified as histidine by trapping experiments with nitrophenyl [ P]-phosphate followed by denaturation. The nucleophilic histidine residue is part of a characteristic amino acid sequence RHGXRXP (using the amino acid single-letter codes where X represents amino acid residues that are not conserved). The acid (or histidine) phosphatases have not been subjected to as much study as APs, but some further mechanistic information has been obtained from X-ray structures, " mutagenesis studies, and LEER analyses. ... 

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