Properties and biosynthesis of a vitamin K-dependent calcium binding protein in bone.
Bone, whether of endochondral or intramembranous origin, contains the vitamin K-dependent calcium binding amino acid residue gamma-carboxyglutamic acid (Gla) in a small, anionic protein we have named osteocalcin. This protein, which constitutes 0.5 to 1.0% of the total bone proteins and about 20% of the noncollagenous protein, is extractable by EDTA, and contains at least 90% of bone Gla. Analysis of purified osteocalcin from chicken bone and independent sequence studies of an analogous bovine bone protein show no apparent homology to the Gla-containing region of prothrombin. Chicken osteocalcin specifically binds 2 moles of calcium ions per 6,500 g protein. Employing coumarin drugs and vitamin K-deficient diets, vitamin K-dependent osteocalcin biosynthesis has been demonstrated in the chick before and after hatching. Organ cultures of embryonic chick bone show de novo synthesis of osteocalcin, and microsomal preparations of embryonic bone also exhibit vitamin K-dependent carboxylase activity. In addition to the presence of osteocalcin in bone, a Gla-protein of unknown function is present in normal nonmineralized kidney cortex. Furthermore, in various pathological calcifications such as hard atheromatous plaque, renal calculi, and subcutaneous ectopic calcifications other Gla-proteins are found, thus implicating such proteins and vitamin K in many facets of calcium metabolism.
D015055:1-Carboxyglutamic Acid / Q000378:metabolism; D000818:Animals; D001846:Bone Development; D001842:Bone and Bones / Q000378:metabolism*; D002113:Calcification, Physiologic; D002114:Calcinosis / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002262:Carboxy-Lyases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002645:Chickens; D046508:Culture Techniques; D008861:Microsomes / Q000201:enzymology; D014812:Vitamin K / Q000378:metabolism*
D002352:Carrier Proteins; D014812:Vitamin K; D015055:1-Carboxyglutamic Acid; D002262:Carboxy-Lyases; D002118:Calcium