Correlation of lysyl oxidase activation with the p-phenylenediamine oxidase activity (ceruloplasmin) in serum.

Abstract

A dietary deficiency in copper decreases the lysyl oxidase activity in aortic tissue of growing chickens. The decrease has been correlated with a lowering of serum copper and ceruloplasmin (measured as PPD oxidase activity). Injections of CuSO, restored enzyme function and brought serum copper and ceruloplasmin levels back to normal. How- ever, when the CuSO., was given to chicks that had received two injections of estradiol-17/3, a much stronger increase in lysyl oxidase in response to CuSO, was observed. The enhanced response correlated with an enhanced increase in ceruloplasmin, linking the serum copper protein with the restoration of lysyl oxidase activity. Lysyl oxidase is a copper-dependent en- zyme. It requires copper to function as a catalyst and to maintain a constant level of activity in aortic tissue. The enzyme catalyzes the formation of allysines, the ac- tive aldehyde centers which give rise to crosslinks in collagen and elastin (1). Lysyl oxidase activity fails in animals that are fed diets low in copper, but is restored by re- feeding copper-supplemented diets or in- jecting CuSO, intraperitoneally (2). The close interplay between copper and an as- sociated metalloenzyme is evident. Not so evident, however, is a biochemical under- standing of the mechanism. Very little is known of the process by which metal ions are transported in the blood to the tissues. Even less is known of how metal ions enter cells to engage the binding sites of enzymes. The lysyl oxidase system may provide a model for elucidating such events, at least to the extent of iden- tifying transport components for delivering copper to the metal-free enzyme. Studies in vitro have suggested that lysyl oxidase acti- vation coincides with the binding of copper ions to newly synthesized molecules of apoenzyme (3). Although copper ions may limit the activation of this enzyme in vitro, free metal ions are not likely to be the im- mediate source of the protein-bound metal in the intact animal; a serum protein or a complex of copper with specific amino acids (4) probably performs this function in vivo. The present study examines this