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. 1969 Nov;48(11):2114–2123. doi: 10.1172/JCI106178

Lipid metabolism in human platelets

II. De novo phospholipid synthesis and the effect of thrombin on the pattern of synthesis

Nancy Lewis 1,2, Philip W Majerus 1,2
PMCID: PMC297465  PMID: 4309956

Abstract

Washed human platelets were incubated with radioactive glycerol; the platelets were able to synthesize de novo the major phosphoglycerides including phosphatidic acid, phosphatidylinositol, phosphatidyl choline, phosphatidyl ethanolamine, and phosphatidyl serine. The specific activities of the phosphoglycerides obtained after glycerol incorporation indicate that phosphatidic acid, phosphatidylinositol, and phosphatidyl choline are metabolically active relative to phosphatidyl ethanolamine and that formation of phosphatidyl serine occurs to a much more limited extent. When platelets were incubated with bovine thrombin, 1 U/ml, the pattern of glycerol incorporation into phospholipid was changed. There was a 3-fold decrease in the total incorporation into lipid in 30 min with a relative 5-fold decreased incorporation into phosphatidyl choline and phosphatidyl ethanolamine and a 5-fold increased incorporation into phosphatidyl serine. The increased incorporation into phosphatidyl serine. The increased incorporation into phosphatidyl serine was maximal within the first 2 min but was transient, since within 20 minutes, the rate returned to that seen in platelets incubated with glycerol alone. Purified human thrombin also produced this same effect on phospholipid synthesis in platelets. Trypsin produced effects on phosphoglyceride formation similar to those seen with thrombin, and the trypsin-induced effect was inhibited by prior incubation of trypsin with soybean trypsin inhibitor, suggesting that proteolysis may be required for the observed effects on phospholipid synthesis.

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Selected References

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

  1. ABRAMSON D., BLECHER M. QUANTITATIVE TWO-DIMENSIONAL THIN-LAYER CHROMATOGRAPHY OF NATURALLY OCCURRING PHOSPHOLIPIDS. J Lipid Res. 1964 Oct;5:628–631. [PubMed] [Google Scholar]
  2. AMES B. N., DUBIN D. T. The role of polyamines in the neutralization of bacteriophage deoxyribonucleic acid. J Biol Chem. 1960 Mar;235:769–775. [PubMed] [Google Scholar]
  3. BETTEX-GALLAND M., LUSCHER E. F. Studies on the metabolism of human blood platelets in relation to clot retraction. Thromb Diath Haemorrh. 1960 Mar 1;4:178–195. [PubMed] [Google Scholar]
  4. BORN G. V. Changes in the distribution of phosphorus in platelet-rich plasma during clotting. Biochem J. 1958 Apr;68(4):695–704. doi: 10.1042/bj0680695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. BUBLITZ C., KENNEDY E. P. Synthesis of phosphatides in isolated mitochondria. III. The enzymatic phosphorylation of glycerol. J Biol Chem. 1954 Dec;211(2):951–961. [PubMed] [Google Scholar]
  6. DAWSON R. M. The measurement of 32P labelling of individual kephalins and lecithin in a small sample of tissue. Biochim Biophys Acta. 1954 Jul;14(3):374–379. doi: 10.1016/0006-3002(54)90195-x. [DOI] [PubMed] [Google Scholar]
  7. Deykin D., Desser R. K. The incorporation of acetate and palmitate into lipids by human platelets. J Clin Invest. 1968 Jul;47(7):1590–1602. doi: 10.1172/JCI105851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. FIRKIN B. G., WILLIAMS W. J. The incorporation of radioactive phosphorus into the phospholipids of human leukemic leukocytes and platelets. J Clin Invest. 1961 Feb;40:423–432. doi: 10.1172/JCI104270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ganguly P. Studies on human platelet proteins. II. Effect of thrombin. Blood. 1969 Apr;33(4):590–597. [PubMed] [Google Scholar]
  10. Goldfine H. Lipid chemistry and metabolism. Annu Rev Biochem. 1968;37:303–330. doi: 10.1146/annurev.bi.37.070168.001511. [DOI] [PubMed] [Google Scholar]
  11. HANES C. S., ISHERWOOD F. A. Separation of the phosphoric esters on the filter paper chromatogram. Nature. 1949 Dec 31;164(4183):1107-12, illust. doi: 10.1038/1641107a0. [DOI] [PubMed] [Google Scholar]
  12. HASLAM R. J. ROLE OF ADENOSINE DIPHOSPHATE IN THE AGGREGATION OF HUMAN BLOOD-PLATELETS BY THROMBIN AND BY FATTY ACIDS. Nature. 1964 May 23;202:765–768. doi: 10.1038/202765a0. [DOI] [PubMed] [Google Scholar]
  13. HOKIN L. E., HOKIN M. R. Phosphoinositides and protein secretion in pancreas slices. J Biol Chem. 1958 Oct;233(4):805–810. [PubMed] [Google Scholar]
  14. Hennes A. R., Awai K., Hammarstrand K., Duboff G. S. Carbon-14 in carboxyl carbon of fatty acids formed by platelets from normal and diabetic subjects. Nature. 1966 May 21;210(5038):839–841. doi: 10.1038/210839a0. [DOI] [PubMed] [Google Scholar]
  15. KOSTKA V., CARPENTER F. H. INHIBITION OF CHYMOTRYPSIN ACTIVITY IN CRYSTALLINE TRYPSIN PREPARATIONS. J Biol Chem. 1964 Jun;239:1799–1803. [PubMed] [Google Scholar]
  16. Karpatkin S., Langer R. M. Biochemical energetics of simulated platelet plug formation. Effect of thrombin, adenosine diphosphate, and epinephrine on intra- and extracellular adenine nucleotide kinetics. J Clin Invest. 1968 Sep;47(9):2158–2168. doi: 10.1172/JCI105902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Majerus P. W., Lastra R. Fatty acid biosynthesis in human leukocytes. J Clin Invest. 1967 Oct;46(10):1596–1602. doi: 10.1172/JCI105651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Majerus P. W., Smith M. B., Clamon G. H. Lipid metabolism in human platelets. I. Evidence for a complete fatty acid synthesizing system. J Clin Invest. 1969 Jan;48(1):156–164. doi: 10.1172/JCI105964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Marcus A. J. The role of lipids in blood coagulation. Adv Lipid Res. 1966;4:1–37. [PubMed] [Google Scholar]
  20. Marcus A. J., Zucker-Franklin D., Safier L. B., Ullman H. L. Studies on human platelet granules and membranes. J Clin Invest. 1966 Jan;45(1):14–28. doi: 10.1172/JCI105318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pittman J. G., Martin D. B. Fatty acid biosynthesis in human erythrocytes: evidence in mature erythrocytes for an incomplete long chain fatty acid synthesizing system. J Clin Invest. 1966 Feb;45(2):165–172. doi: 10.1172/JCI105328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Warshaw A. L., Laster L., Shulman N. R. The stimulation by thrombin of glucose oxidation in human platelets. J Clin Invest. 1966 Dec;45(12):1923–1934. doi: 10.1172/JCI105497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Yin E. T., Wessler S. Bovine thrombin and activated factor X. Separation and purification. J Biol Chem. 1968 Jan 10;243(1):112–117. [PubMed] [Google Scholar]

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