The inhibition of alkaline phosphatase by beryllium.

Recent clinical reports of pulmonary disease occurring in workers in the beryllium industry have stimulated new interest in the biochemical action of this element (for a complete bibliography, see (1)). Although it has not been possible to produce in animals pathological conditions identical with those Eeen in beryllium workers, experimental administration of beryllium and its compounds has resulted in a variety of lesions involving various organs and tissues. Of these lesions those affecting the skeletal system are of prime biochemical interest. Experimental rickets have been produced by feeding a diet which contains an excess of beryllium over the amount of phosphate ingested (2-5). Most authors are agreed that in this case the production of rickets is due, at least in part, to the low solubility of beryllium phosphate which, precipitated in the intestine, becomes unavailable for absorption. Nevertheless, in vitro experiments by Sobel et al. (5) indicate that a local factor is also operative in preventing calcification in beryllium rickets. A different effect of beryllium on bones has been demonstrated in rabbits by Gardner and Heslington (6) who observed eburnation with subsequent tumor formation following injection of sparsely soluble beryllium compounds. In view of the role which phosphatase plays in the formation of bone, it appeared possible that disturbances of normal ossification might depend on interference of beryllium with the action of this enzyme. Guyatt, Kay, and Branion (2), without giving experimental evidence, stated that “Be++ was occasionally strongly activating” to phosphatase. Cloetens (7), who studied the effect of various metals on alkaline phosphatase, reported inactivation of the enzyme by 1O-a M solution of beryllium chloride. Greenstein et al. (8) observed an inhibiting effect of beryllium on the format.ion of ammonia and inorganic phosphate from nucleic acids by crude tissue extracts. The following report represents an investigation of the action of beryllium on phosphatase.