Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1971 May;50(5):961–969. doi: 10.1172/JCI106589

Inorganic pyrophosphate in plasma in normal persons and in patients with hypophosphatasia, osteogenesis imperfecta, and other disorders of bone

R G G Russell 1,2,3,4, S Bisaz 1,2,3,4, A Donath 1,2,3,4, D B Morgan 1,2,3,4, H Fleisch 1,2,3,4
PMCID: PMC292015  PMID: 4324072

Abstract

An isotope dilution method, using 32P-labeled pyrophosphate, has been developed for the measurement of inorganic pyrophosphate (PP1) in human plasma. The specificity of the method was better than 90% as assessed by elution patterns during ion-exchange chromatography, by paper chromatography, and by incubation with inorganic pyrophosphatase. The 99% confidence limits for a single estimation of plasma PP1 was ±13%. There were no differences in plasma PP1 between men and women, but the values in young people (0-15 yr) were slightly higher than in older people. The mean concentration (±SE) of PP1 in the plasma of 73 men and women was 3.50 ±0.11 μmoles/liter (0.217 ±0.007 μg P/ml) and the normal range (99% limits) was 1.19-5.65 μmoles/liter (0.074-0.350 μg P/ml).

It has been suggested that PP1 may be important in calcium metabolism because PP1 can prevent the precipitation of calcium phosphates in vitro and in vivo, and can slow the rates at which hydroxyapatite crystals grow and dissolve. Plasma PP1 was therefore measured in several disorders of bone. Normal values were found in osteogenesis imperfecta, osteopetrosis, “acute” osteoporosis, and primary hyperparathyroidism. Plasma PP1 was invariably raised in hypophosphatasia. The excess of PP1 in plasma might be the cause of the defective mineralization in hypophosphatasia and the function of alkaline phosphatase in bone may be to act as a pyrophosphatase at sites of calcium deposition.

Full text

PDF
961

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bongiovanni A. M., Album M. M., Root A. W., Hope J. W., Marino J., Spencer D. M. Studies in hypophosphatasia and response to high phosphate intake. Am J Med Sci. 1968 Mar;255:163–170. doi: 10.1097/00000441-196803000-00003. [DOI] [PubMed] [Google Scholar]
  2. DENT C. E., FRIEDMAN M. IDIOPATHIC JUVENILE OSTEOPOROSIS. Q J Med. 1965 Apr;34:177–210. [PubMed] [Google Scholar]
  3. Eaton H., Moss D. W. Partial purification and some properties of human bone alkaline phosphatase. Enzymologia. 1968 Jul 31;35(1):31–39. [PubMed] [Google Scholar]
  4. FLEISCH H., BISAZ S. DIE PYROPHOSPHATAUSSCHEIDUNG IM HARN BEIM GESUNDEN MENSCHEN. Helv Physiol Pharmacol Acta. 1963;21:88–94. [PubMed] [Google Scholar]
  5. FLEISCH H., BISAZ S. Isolation from urine of pyrophosphate, a calcification inhibitor. Am J Physiol. 1962 Oct;203:671–675. doi: 10.1152/ajplegacy.1962.203.4.671. [DOI] [PubMed] [Google Scholar]
  6. FLEISH H., NEUMAN W. F. Mechanisms of calcification: role of collagen, polyphosphates, and phosphatase. Am J Physiol. 1961 Jun;200:1296–1300. doi: 10.1152/ajplegacy.1961.200.6.1296. [DOI] [PubMed] [Google Scholar]
  7. FRASER D. Hypophosphatasia. Am J Med. 1957 May;22(5):730–746. doi: 10.1016/0002-9343(57)90124-9. [DOI] [PubMed] [Google Scholar]
  8. Fernley H. N., Bisaz S. Studies on alkaline phosphatase. Phosphorylation of calf-intestinal alkaline phosphatase by 32P-labelled pyrophosphate. Biochem J. 1968 Mar;107(2):279–283. doi: 10.1042/bj1070279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fernley H. N., Walker P. G. Studies on alkaline phosphatase. Inhibition by phosphate derivatives and the substrate specificity. Biochem J. 1967 Sep;104(3):1011–1018. doi: 10.1042/bj1041011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fleisch H., Maerki J., Russell R. G. Effect of pyrophosphate on dissolution of hydroxyapatite and its possible importance in calcium homeostasis. Proc Soc Exp Biol Med. 1966 Jun;122(2):317–320. doi: 10.3181/00379727-122-31123. [DOI] [PubMed] [Google Scholar]
  11. Fleisch H., Russell R. G., Straumann F. Effect of pyrophosphate on hydroxyapatite and its implications in calcium homeostasis. Nature. 1966 Nov 26;212(5065):901–903. doi: 10.1038/212901a0. [DOI] [PubMed] [Google Scholar]
  12. Fleisch H., Straumann F., Schenk R., Bisaz S., Allgöwer M. Effect of condensed phosphates on calcification of chick embryo femurs in tissue culture. Am J Physiol. 1966 Sep;211(3):821–825. doi: 10.1152/ajplegacy.1966.211.3.821. [DOI] [PubMed] [Google Scholar]
  13. Gabbiani G., Jacqmin M. L., Richard R. M. Soft-tissue calcification induced by rare earth metals and its prevention by sodium pyrophosphate. Br J Pharmacol Chemother. 1966 May;27(1):1–9. doi: 10.1111/j.1476-5381.1966.tb01636.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. HALL R. J. An improved method for the micro-determination of inorganic phosphate in small volumes of biological fluids. J Med Lab Technol. 1963 Apr;20:97–103. [PubMed] [Google Scholar]
  15. Jung A., Russel R. G., Bisaz S., Morgan D. B., Fleisch H. Fate of intravenously injected pyrophosphate-32P in dogs. Am J Physiol. 1970 Jun;218(6):1757–1764. doi: 10.1152/ajplegacy.1970.218.6.1757. [DOI] [PubMed] [Google Scholar]
  16. KUNITZ M. An improved method for isolation of crystalline pyrophosphatase from baker's yeast. Arch Biochem Biophys. 1961 Feb;92:270–272. doi: 10.1016/0003-9861(61)90348-4. [DOI] [PubMed] [Google Scholar]
  17. KUNITZ M. Hydrolysis of adenosine triphosphate by crystalline yeast pyrophosphatase. Effect of zinc and magnesium ions. J Gen Physiol. 1962 Mar;45(4):31–46. doi: 10.1085/jgp.45.4.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Moss D. W., Eaton R. H., Smith J. K., Whitby L. G. Association of inorganic-pyrophosphatase activity with human alkaline-phosphatase preparations. Biochem J. 1967 Jan;102(1):53–57. doi: 10.1042/bj1020053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. RUSSELL R. G. EXCRETION OF INORGANIC PYROPHOSPHATE IN HYPOPHOSPHATASIA. Lancet. 1965 Sep 4;2(7410):461–464. doi: 10.1016/s0140-6736(65)91422-4. [DOI] [PubMed] [Google Scholar]
  20. Russell R. G., Bisaz S., Fleisch H. Pyrophosphate and diphosphonates in calcium metabolism and their possible role in renal failure. Arch Intern Med. 1969 Nov;124(5):571–577. [PubMed] [Google Scholar]
  21. Schibler D., Russell R. G., Fleisch H. Inhibition by pyrophosphate and polyphosphate of aortic calcification induced by vitamin D3 in rats. Clin Sci. 1968 Oct;35(2):363–372. [PubMed] [Google Scholar]
  22. Solomons C. C., Styner J. Osteogenesis imperfecta: effect of magnesium administration on pyrophosphate metabolism. Calcif Tissue Res. 1969;3(4):318–326. doi: 10.1007/BF02058674. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES