Value of differential thermostability, urea inhibition, and gel filtration of alkaline phosphatase in the identification of disease states.

The problem of identifying the source of raised serum alkaline phosphatase level is one which often baffles the clinician. Of the many methods so far investigated, none has been adapted to clinical work generally. Starch gel studies, while valuable in some hands, have at times produced conflicting results, particularly as regards the origin of normal serum phosphatase. Chiandussi, Greene, and Sherlock (1962) and Kowlessar, Haeffner, and Riley (1961), using starch gel electrophoresis, Dunne, Fennelly, and McGeeney (1967), using gel filtration, and Posen, Neale, and Clubb (1965), using heat inactivation, suggested an osseous origin for control serum enzyme, while Hodson, Latner, and Raine (1962) using similar techniques, and Yong (1967), using agar gel, concluded 'normal serum phosphatase is of hepatic origin'. Immunological studies of Boyer (1963) have shown definite cross reaction between skeletal and hepatic phosphatase, so that method is not suitable for application to clinical work in terms of differential diagnosis. Inhibition of phosphatase by L-phenylalanine was shown by Fishman, Green, and Inglis (1962) to be specific for intestinal enzyme though later publications show definite inhibition of placental (Yong, 1967) and hepatic enzymes (Posen, Neale, Birkett, and Brudenell-Woods, 1967). L-Phenylalanine-sensitive phosphatase contributes 10 to 20% of total phosphatase in control serum, the actual amount being related to blood group status (Langman, Leuthold, Robson, Harris, Luffman, and Harris, 1966), and the presence of a slow moving component on cellulose acetate electrophoresis (Posen et al, 1967). The purpose of this communication is to present observations on serum alkaline phosphatase isoenzyme patterns as reflected by (a) varying molecular size, (b) differential heat inactivation, and (c) differential urea inhibition, in so far as either alone