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Direct demonstration that the vitamin k‐dependent bone gla protein is incompletely γ‐carboxylated in humans
Author(s) -
Cairns James R.,
Price Paul A.
Publication year - 1994
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650091220
Subject(s) - chemistry , endocrinology , biochemistry , medicine
Incomplete vitamin K‐dependent γ‐carboxylation has been found in bone Gla protein (BGP) isolated from each of 20 different human bone samples. Using N‐terminal protein sequencing of the methyl‐esterified protein (Anal Biochem 1991;199:93‐97), a method that directly measures the percentage of γ‐carboxylation at each target glutamate residue, the extent of incomplete BGP γ‐carboxylation was found to depend strongly on sequence position, with (x̄ + SD) 67 + 14% γ‐carboxylation at residue 17, 88 + 9% γ‐carboxylation at residue 21, and 93 + 4% γ‐carboxylation at residue 24. There is a strong correlation between the incomplete γ‐carboxylation at glutamate residues 17 and 21 for BGP purified from the 20 bone samples ( p < 0.001), which suggests that individual differences in the efficiency of BGP γ‐carboxylation during synthesis probably cause the observed differences in percentage BGP γ‐carboxylation between bone samples. These results have been interpreted using a kinetic treatment of γ‐carboxylation. This treatment predicts the existence of differences in the extent of γ‐carboxylation between glutamate residues in BGP, as well as the correlation between percentage carboxylation at Glu 17 and Glu 21 . Although the molecular basis of incomplete BGP γ‐carboxylation is at present unknown, if incomplete BGP γ‐carboxylation were caused only by differences in the availability of vitamin K in bone cells, this kinetic treatment predicts that the range in BGP γ‐carboxylation observed in the 20 human bone samples studied here could be explained by a relatively modest fivefold range in the vitamin K levels of these individuals.