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Origin of the vitamin K-dependent bone protein found in plasma and its clearance by kidney and bone.
Open accessAbstract
The vitamin K-dependent bone protein (bone Gla protein, BGP) that is found in serum comes from new cellular synthesis rather than from the release of bone matrix protein during bone resorption. This is shown by the fact hat Warfarin administration to normal rats completely shifts the chemical nature of serum BGP within 3 h, from a form which has y-carboxyglutamic acid to one which does not. Since the BGP isolated from the bones of rats 8 h after Warfarin injection is fully y-carboxylated, the abnormal serum BGP could not have come from the resorption of bone matrix. The origin of serum BGP in new cellular synthesis is also supported by the fact that administration of vitamin K1 to a chronically Warfarin-treated rat causes serum levels of fully y-carboxylated BGP to return to normal levels within 16 h. Since total BGP levels in these bones are only 1.5% of normal at 16 h after vitamin K1 administration, the normal BGP levels in serum cannot be due to the release of bone matrix BGP during bone resorption. Injected BGP is cleared from the serum rapidly, with a half-time of 4 min. The primary mode of clearance is kidney filtration, as shown by the accumulation of 12‘1label in the kidney within minutes of 12’II-BGP injection. The importance of the kidney in the clearance of BGP from serum is also demonstrated by the fact that nephrectomy causes serum BGP levels to increase 8-fold in 4 h. Clearance of ‘Z‘I-BGP by bone is quantitatively less important than is clearance by the kidney, accounting for only ?% of the injected label in 1-month-old rats. The accumulation of 1261-labeled BGP in bone, as well as the binding of BGP to hydroxyapatite, requires the presence of y-carboxyglutamic acid in the protein. These results, together with other observations, support the hypothesis that the role of y-carboxyglutamic acid in BGP is to enable the protein to bind strongly to hydroxyapatite and, by this association, accumulate in bone.
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Citations
Cited by
Human growth hormone and human aging
CORPAS, E., HARMAN, S. M., & BLACKMAN, M. R. (1993) · Endocrine Reviews · doi:10.1210/edrv-14-1-20 · Cited by 911
SERUM BONE GLA-PROTEIN: A SPECIFIC MARKER FOR BONE FORMATION IN POSTMENOPAUSAL OSTEOPOROSIS
Brown, J. P., Malaval, L., Chapuy, M. C., Delmas, P. D., Edouard, C., & Meunier, P. J. (1984) · The Lancet · doi:10.1016/s0140-6736(84)92506-6 · Cited by 668
Primary structure of bovine matrix Gla protein, a new vitamin K-dependent bone protein.
Price, P. A., & Williamson, M. K. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)95688-7 · Cited by 277
Self-citationDifferences in basal and postexercise osteocalcin levels in athletic and nonathletic humans
Nishiyama, S., Tomoeda, S., Ohta, T., Higuchi, A., & Matsuda, I. (1988) · Calcified Tissue International · doi:10.1007/bf02571312 · Cited by 86
Sato, Y., Honda, Y., Kuno, H., & Oizumi, K. (1998) · Bone · doi:10.1016/s8756-3282(98)00108-2 · Cited by 77
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Metadata
- Authors
- Price, P. A., Williamson, M. K., & Lothringer, J. W.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1981-12
- Volume
- 256
- Issue
- 24
- Pages
- 12760-12766
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1597802619
- Cited by
- 485
- References
- 0
- FWCI
- 8.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Price, P. A., Williamson, M. K., & Lothringer, J. W. (1981). Origin of the vitamin K-dependent bone protein found in plasma and its clearance by kidney and bone. Journal of Biological Chemistry. https://doi.org/10.1016/s0021-9258(18)42960-2
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
