Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1975 Dec;56(6):1481–1490. doi: 10.1172/JCI108229

Conversion of very low density lipoprotein to low density lipoprotein. A metabolic study of apolipoprotein B kinetics in human subjects.

G Sigurdsson, A Nicoll, B Lewis
PMCID: PMC333126  PMID: 172533

Abstract

The interrelationship between apolipoprotein B in very low density lipoprotein (VLDL-B) and in low density lipoprotein (LDL-B) was studied in seven normal and hyperlipidemic men and women, with purified radioiodinated VLDL. The time-course of the appearance of radioactivity in LDL was followed. As the specific activity curves intersected at the masimal height of the LDL-B curve, it was inferred that all or most LDL-B peptide is derived from VLDL-B peptide. This transfer was further quantitated in seven normotriglyceridemic subjects by simultaneous i.v. injection of purified 131I-VLDL and 125I-LDL. By a deconvolution method, a quantitative description of the rate of entry of 131Ivldl-b into 131I-LDL-B was derived by analysis of 131I-LDL-B and 125I-ldl-b radioactivity in plasma. The results indicate that approximately 90% of VLDL-B mass is converted into LDL-B in subjects with normal serum triglyceride concentrations. The synthetic rates of VLDL-B and LDL-B peptide were simultaneously measured in six normal subjects, and two patients with heterozygous familial hypercholesterolemia (type IIa). The turnover rates for VLDL-B and LDL-B peptide were similar in these subjects. The findings in the three parts of this study were consistent with the view that most if not all VLDL-B is converted into LDL-B peptide, and most if not all LDL-B is derived from VLDL-B peptide in normotriglyceridemic subjects.

Full text

PDF
1481

Selected References

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

  1. Beaumont J. L., Carlson L. A., Cooper G. R., Fejfar Z., Fredrickson D. S., Strasser T. Classification of hyperlipidaemias and hyperlipoproteinaemias. Bull World Health Organ. 1970;43(6):891–915. [PMC free article] [PubMed] [Google Scholar]
  2. Bilheimer D. W., Eisenberg S., Levy R. I. The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim Biophys Acta. 1972 Feb 21;260(2):212–221. doi: 10.1016/0005-2760(72)90034-3. [DOI] [PubMed] [Google Scholar]
  3. Birge S. J., Peck W. A., Berman M., Whedon G. D. Study of calcium absorption in man: a kinetic analysis and physiologic model. J Clin Invest. 1969 Sep;48(9):1705–1713. doi: 10.1172/JCI106136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown W. V., Levy R. I., Fredrickson D. S. Studies of the proteins in human plasma very low density lipoproteins. J Biol Chem. 1969 Oct 25;244(20):5687–5694. [PubMed] [Google Scholar]
  5. Cramp D. G., Robertson G. The fluorometric assay of triglyceride by a semiautomated method. Anal Biochem. 1968 Oct 24;25(1):246–251. doi: 10.1016/0003-2697(68)90097-3. [DOI] [PubMed] [Google Scholar]
  6. Eisenberg S., Bilheimer D. W., Levy R. I., Lindgren F. T. On the metabolic conversion of human plasma very low density lipoprotein to low density lipoprotein. Biochim Biophys Acta. 1973 Dec 20;326(3):361–377. doi: 10.1016/0005-2760(73)90138-0. [DOI] [PubMed] [Google Scholar]
  7. Eisenberg S., Rachmilewitz D. Metabolism of rat plasma very low density lipoprotein. I. Fate in circulation of the whole lipoprotein. Biochim Biophys Acta. 1973 Dec 20;326(3):378–390. doi: 10.1016/0005-2760(73)90139-2. [DOI] [PubMed] [Google Scholar]
  8. GITLIN D., CORNWELL D. G., NAKASATO D., ONCLEY J. L., HUGHES W. L., Jr, JANEWAY C. A. Studies on the metabolism of plasma proteins in the nephrotic syndrome. II. The lipoproteins. J Clin Invest. 1958 Feb;37(2):172–184. doi: 10.1172/JCI103596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. GRAHAM D. M., LYON T. P., GOFMAN J. W., JONES H. B., YANKLEY A., SIMONTON J., WHITE S. Blood lipids and human atherosclerosis. II. The influence of heparin upon lipoprotein metabolism. Circulation. 1951 Nov;4(5):666–673. doi: 10.1161/01.cir.4.5.666. [DOI] [PubMed] [Google Scholar]
  10. GREGERSEN M. I., RAWSON R. A. Blood volume. Physiol Rev. 1959 Apr;39(2):307–342. doi: 10.1152/physrev.1959.39.2.307. [DOI] [PubMed] [Google Scholar]
  11. GUSTAFSON A., ALAUPOVIC P., FURMAN R. H. STUDIES OF THE COMPOSITION AND STRUCTURE OF SERUM LIPOPROTEINS: ISOLATION, PURIFICATION, AND CHARACTERIZATION OF VERY LOW DENSITY LIPOPROTEINS OF HUMAN SERUM. Biochemistry. 1965 Mar;4:596–605. doi: 10.1021/bi00879a033. [DOI] [PubMed] [Google Scholar]
  12. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hamilton R. L. Synthesis and secretion of plasma lipoproteins. Adv Exp Med Biol. 1972;26(0):7–24. doi: 10.1007/978-1-4684-7547-0_2. [DOI] [PubMed] [Google Scholar]
  14. Hart H., Spencer H. Rate of initial entry of Ca17 and Sr85 from the intestine into the vascular space. Proc Soc Exp Biol Med. 1967 Nov;126(2):365–371. doi: 10.3181/00379727-126-32447. [DOI] [PubMed] [Google Scholar]
  15. Kane J. P. A rapid electrophoretic technique for identification of subunit species of apoproteins in serum lipoproteins. Anal Biochem. 1973 Jun;53(2):350–364. doi: 10.1016/0003-2697(73)90081-x. [DOI] [PubMed] [Google Scholar]
  16. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  17. Langer T., Strober W., Levy R. I. The metabolism of low density lipoprotein in familial type II hyperlipoproteinemia. J Clin Invest. 1972 Jun;51(6):1528–1536. doi: 10.1172/JCI106949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lee D. M., Alaupović P. Composition and concentration of apolipoproteins in very-low-and low-density lipoproteins of normal human plasma. Atherosclerosis. 1974 May-Jun;19(3):501–520. [PubMed] [Google Scholar]
  19. Levy R. S., Lynch A. C., McGee E. D., Mehl J. W. Amino acid composition of the proteins from chylomicrons and human serum lipoproteins. J Lipid Res. 1967 Sep;8(5):463–472. [PubMed] [Google Scholar]
  20. Lewis B., Chait A., Wootton I. D., Oakley C. M., Krikler D. M., Sigurdsson G., February A., Maurer B., Birkhead J. Frequency of risk factors for ischaemic heart-disease in a healthy British population. With particular reference to serum-lipoprotein levels. Lancet. 1974 Feb 2;1(7849):141–146. doi: 10.1016/s0140-6736(74)92438-6. [DOI] [PubMed] [Google Scholar]
  21. MATTHEWS C. M. The theory of tracer experiments with 131I-labelled plasma proteins. Phys Med Biol. 1957 Jul;2(1):36–53. doi: 10.1088/0031-9155/2/1/305. [DOI] [PubMed] [Google Scholar]
  22. Margolis S., Langdon R. G. Studies on human serum beta-1-lipoprotein. I. Amino acid composition. J Biol Chem. 1966 Jan 25;241(2):469–476. [PubMed] [Google Scholar]
  23. Quarfordt S. H., Frank A., Shames D. M., Berman M., Steinberg D. Very low density lipoprotein triglyceride transport in type IV hyperlipoproteinemia and the effects of carbohydrate-rich diets. J Clin Invest. 1970 Dec;49(12):2281–2297. doi: 10.1172/JCI106448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Scanu A. M., Edelstein C. Solubility in aqueous solutions of ethanol of the small molecular weight peptides of the serum very low density and high density lipoproteins: relevance to the recovery problem during delipidation of serum lipoproteins. Anal Biochem. 1971 Dec;44(2):576–588. doi: 10.1016/0003-2697(71)90247-8. [DOI] [PubMed] [Google Scholar]
  25. Schaffner W., Weissmann C. A rapid, sensitive, and specific method for the determination of protein in dilute solution. Anal Biochem. 1973 Dec;56(2):502–514. doi: 10.1016/0003-2697(73)90217-0. [DOI] [PubMed] [Google Scholar]
  26. Windmueller H. G., Herbert P. N., Levy R. I. Biosynthesis of lymph and plasma lipoprotein apoproteins by isolated perfused rat liver and intestine. J Lipid Res. 1973 Mar;14(2):215–223. [PubMed] [Google Scholar]
  27. ZILVERSMIT D. B. The design and analysis of isotope experiments. Am J Med. 1960 Nov;29:832–848. doi: 10.1016/0002-9343(60)90117-0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES