Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1972 Jun;51(6):1528–1536. doi: 10.1172/JCI106949

The metabolism of low density lipoprotein in familial type II hyperlipoproteinemia

Terry Langer 1,2, Warren Strober 1,2, Robert I Levy 1,2
PMCID: PMC292290  PMID: 4336943

Abstract

The metabolism of low density lipoprotein (LDL, beta lipoprotein) was studied in 10 normal individuals and 10 patients with familial type II hyperlipoproteinemia using purified radioiodinated LDL. Over 97% of the label was bound to the protein moiety of LDL and therefore the turnover data reflect the fate and distribution of LDL-apoprotein. Comparison of the metabolic behavior of biologically screened and unscreened labeled LDL preparations in dogs as well as the analysis of the urinary excretion of radioiodide derived from labeled LDL degradation in humans indicated that no significant denaturation resulted from the isolation, purification, and labeling techniques.

The plasma concentration of LDL-cholesterol in normals was 105±21 mg/100 ml (mean ±1 SD) in contrast to 254±47 mg/100 mg in patients with type II hyperlipoproteinemia; these values corresponded to LDL-apoprotein concentrations of 63±13 mg/100 ml and 153±30 mg/100 ml, respectively. Despite these differences in concentration, the synthetic rate of LDL-apoprotein in both groups was not significantly different (14.43±1.75 mg/kg per day in normals vs. 15.01±1.71 mg/kg per day in type II) nor was there any difference in the fraction of the total exchangeable LDL which was in the intravascular space (68.4±4.3% vs. 73.3±5.2%). However, the fractional catabolic rate of LDL in normal individuals differed significantly from that of patients with type II hyperlipoproteinemia (0.462±0.077/day in normals vs. 0.237±0.044/day in type II) and correspondingly the biological half-life of LDL was significantly prolonged (3.08±0.35 days normals vs. 4.68±0.44 days in type II).

These data indicate that the pathologic elevation of plasma LDL concentration in the individuals with type II hyperlipoproteinemia studied here is due to a decreased fractional rate of LDL degradation rather than to an abnormality of LDL synthesis. This defect of catabolism may be the primary defect in type II hyperlipoproteinemia or, alternatively, may be secondary to an underlying abnormality in lipid metabolism.

Full text

PDF
1528

Images in this article

1532Image
on p.1532

Selected References

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

  1. Adams G. H., Schumaker V. N. Rapid molecular weight estimates for low-density lipoproteins. Anal Biochem. 1969 Apr 11;29(1):117–129. doi: 10.1016/0003-2697(69)90014-1. [DOI] [PubMed] [Google Scholar]
  2. BARTH W. F., WOCHNER R. D., WALDMANN T. A., FAHEY J. L. METABOLISM OF HUMAN GAMMA MACROGLOBULINS. J Clin Invest. 1964 Jun;43:1036–1048. doi: 10.1172/JCI104987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BARTLETT G. R. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed] [Google Scholar]
  4. BRAGDON J. H., HAVEL R. J., BOYLE E. Human serum lipoproteins. I. Chemical composition of four fractions. J Lab Clin Med. 1956 Jul;48(1):36–42. [PubMed] [Google Scholar]
  5. Fredrickson D. S., Levy R. I., Lees R. S. Fat transport in lipoproteins--an integrated approach to mechanisms and disorders. N Engl J Med. 1967 Jan 19;276(3):148–contd. doi: 10.1056/NEJM196701192760305. [DOI] [PubMed] [Google Scholar]
  6. GEE D. J., GOLDSTEIN J., GRAY C. H., FOWLER J. F. Biosynthesis of cholesterol in familial hypercholesterolaemic xanthomatosis. Br Med J. 1959 Sep 5;2(5148):341–344. doi: 10.1136/bmj.2.5148.341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Goodman D. S., Noble R. P. Turnover of plasma cholesterol in man. J Clin Invest. 1968 Feb;47(2):231–241. doi: 10.1172/JCI105719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Grundy S. M., Ahrens E. H., Jr Measurements of cholesterol turnover, synthesis, and absorption in man, carried out by isotope kinetic and sterol balance methods. J Lipid Res. 1969 Jan;10(1):91–107. [PubMed] [Google Scholar]
  10. HELLMAN L., ROSENFELD R. S., EIDINOFF M. L., FUKUSHIMA D. K., GALLAGHER T. F., WANG C. I., ADLERSBERG D. Isotopic studies of plasma cholesterol of endogenous and exogenous origins. J Clin Invest. 1955 Jan;34(1):48–60. doi: 10.1172/JCI103062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hurley P. J., Scott P. J. Plasma turnover of Sf 0-9 low-density lipoprotein in normal men and women. Atherosclerosis. 1970 Jan-Feb;11(1):51–76. doi: 10.1016/0021-9150(70)90007-9. [DOI] [PubMed] [Google Scholar]
  12. Kwiterovich P. O., Jr, Sloan H. R., Fredrickson D. S. Glycolipids and other lipid constituents of normal human liver. J Lipid Res. 1970 Jul;11(4):322–330. [PubMed] [Google Scholar]
  13. LEES R. S., HATCH F. T. Sharper separation of lipoprotein species by paper electrophoresis in albumin-containing buffer. J Lab Clin Med. 1963 Mar;61:518–528. [PubMed] [Google Scholar]
  14. 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]
  15. Lees R. S., Ahrens E. H., Jr Fat transport in abetalipoproteinemia. The effects of repeated infusions of beta-lipoprotein-rich plasma. N Engl J Med. 1969 Jun 5;280(23):1261–1266. doi: 10.1056/NEJM196906052802302. [DOI] [PubMed] [Google Scholar]
  16. Levy R. I., Lees R. S., Fredrickson D. S. The nature of pre beta (very low density) lipoproteins. J Clin Invest. 1966 Jan;45(1):63–77. doi: 10.1172/JCI105324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lewis B., Myant N. B. Studies in the metabolism of cholesterol in subjects with normal plasma cholesterol levels and in patients with essential hypercholesterolaemia. Clin Sci. 1967 Apr;32(2):201–213. [PubMed] [Google Scholar]
  18. Lindgren F. T., Jensen L. C., Wills R. D., Freeman N. K. Flotation rates, molecular weights and hydrated densities of the low-density lipoproteins. Lipids. 1969 Sep;4(5):337–344. doi: 10.1007/BF02531003. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. MCFARLANE A. S., TODD D., CROMWELL S. FIBRINOGEN CATABOLISM IN HUMANS. Clin Sci. 1964 Jun;26:415–420. [PubMed] [Google Scholar]
  21. Nestel P. J., Whyte H. M., Goodman D. S. Distribution and turnover of cholesterol in humans. J Clin Invest. 1969 Jun;48(6):982–991. doi: 10.1172/JCI106079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. SPERRY W. M., BRAND F. C. The determination of total lipides in blood serum. J Biol Chem. 1955 Mar;213(1):69–76. [PubMed] [Google Scholar]
  23. Scott P. J., Hurley P. J. Effect of clofibrate on low-density lipoprotein turnover in essential hypercholesterolaemia. J Atheroscler Res. 1969 Jan-Feb;9(1):25–34. doi: 10.1016/s0368-1319(69)80063-3. [DOI] [PubMed] [Google Scholar]
  24. VOLWILER W., GOLDSWORTHY P. D., MACMARTIN M. P., WOOD P. A., MACKAY I. R., FREMONT-SMITH K. Biosynthetic determination with radioactive sulfur of turn-over rates of various plasma proteins in normal and cirrhotic man. J Clin Invest. 1955 Jul;34(7 Pt 1):1126–1146. doi: 10.1172/JCI103162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. WALTON K. W., SCOTT P. J., VERRIERJONES J., FLETCHER R. F., WHITEHEAD T. STUDIES ON LOW-DENSITY LIPOPROTEIN TURNOVER IN RELATION TO ATROMID THERAPY. J Atheroscler Res. 1963 Sep-Dec;3:396–414. doi: 10.1016/s0368-1319(63)80020-4. [DOI] [PubMed] [Google Scholar]
  26. Waldmann T. A., Strober W. Metabolism of immunoglobulins. Prog Allergy. 1969;13:1–110. doi: 10.1159/000385919. [DOI] [PubMed] [Google Scholar]
  27. Walton K. W., Scott P. J., Dykes P. W., Davies J. W. The significance of alterations in serum lipids in thyroid dysfunction. II. Alterations of the metabolism and turnover of 131-I-low-density lipoproteins in hypothyroidism and thyrotoxicosis. Clin Sci. 1965 Oct;29(2):217–238. [PubMed] [Google Scholar]

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

RESOURCES