Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1968 May;47(5):971–982. doi: 10.1172/JCI105812

Direct measurement of the rates of synthesis of plasma proteins in control subjects and patients with gastrointestinal protein loss

R Dean Wochner 1, Sherman M Weissman 1, Thomas A Waldmann 1, Delores Houston 1, Nathaniel I Berlin 1
PMCID: PMC297250  PMID: 5239039

Abstract

The guanido carbon of hepatic arginine is the common precursor of urea and of the arginine of plasma proteins synthesized in the liver. It is possible to measure the momentary synthetic rates of plasma proteins by “pulse labeling” this arginine pool with bicarbonate-14C. In the current study, this method has been adapted in order to use urinary urea data and was applied to control subjects and patients with gastrointestinal protein loss. The assumptions required for this determination are discussed.

There was close agreement between albumin synthetic rates measured by this method and albumin catabolic rates derived from simultaneous albumin-131I studies, supporting the validity of the method and suggesting that there is relatively little fluctuation in the rate of albumin synthesis from time to time. The albumin synthetic rates in six control subjects averaged 5.8 mg/kg per hr, while those of five patients with gastrointestinal protein loss averaged 7.2 mg/kg per hr. Thus in these patients, there was relatively little acceleration of albumin synthesis in response to continued loss of plasma proteins into the gastrointestinal tract.

Fibrinogen synthetic rates averaged 1.9 mg/kg per hr in five control subjects and 3.2 mg/kg per hr in five patients with gastrointestinal protein loss. Transferrin synthetic rates exhibited considerable individual variation in both groups and averaged 0.24 mg/kg per hr in four control subjects and 0.31 mg/kg per hr in five patients with gastrointestinal protein loss.

The method employed in this study offers several advantages in studying plasma protein metabolism. It provides a direct measurement of protein synthesis, applicable to several proteins simultaneously, does not require a long-term steady state in the metabolism of the proteins, and is capable of measuring short-term fluctuations in synthetic rates. Therefore, this approach is applicable to the investigation of the physiological factors controlling the rates of synthesis for plasma proteins.

Full text

PDF
971

Selected References

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

  1. AMRIS A., AMRIS C. J. TURNOVER AND DISTRIBUTION OF 131-IODINE-LABELLED HUMAN FIBRINOGEN. Thromb Diath Haemorrh. 1964 Jul 31;11:404–422. [PubMed] [Google Scholar]
  2. AWAI M., BROWN E. B. Studies of the metabolism of I-131-labeled human transferrin. J Lab Clin Med. 1963 Mar;61:363–396. [PubMed] [Google Scholar]
  3. BAUMAN A., ROTHSCHILD M. A., YALOW R. S., BERSON S. A. Distribution and metabolism of I131 labeled human serum albumin in congestive heart failure with and without proteinuria. J Clin Invest. 1955 Sep;34(9):1359–1368. doi: 10.1172/JCI103184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BEEKEN W. L., VOLWILER W., GOLDSWORTHY P. D., GARBY L. E., REYNOLDS W. E., STOGSDILL R., STEMLER R. S. Studies of I-131-albumin catabolism and distribution in normal young male adults. J Clin Invest. 1962 Jun;41:1312–1333. doi: 10.1172/JCI104594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. BERLIN N. I., TOLBERT B. M., LAWRENCE J. H. Studies in glycine-2-C14 metabolism in man. I. The pulmonary excretion of C14O2. J Clin Invest. 1951 Jan;30(1):73–76. doi: 10.1172/JCI102418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. FAHEY J. L., MCKELVEY E. M. QUANTITATIVE DETERMINATION OF SERUM IMMUNOGLOBULINS IN ANTIBODY-AGAR PLATES. J Immunol. 1965 Jan;94:84–90. [PubMed] [Google Scholar]
  7. FREEMAN T., MATTHEWS C. M. Analysis of the behaviour of I 131-albumin in the normal subject and nephrotic patient. Strahlentherapie. 1958;107(SONDERBD):283–289. [PubMed] [Google Scholar]
  8. GITLIN D., JANEWAY C. A., FARR L. E. Studies on the metabolism of plasma proteins in the nephrotic syndrome. I. Albumin, gamma-globulin and iron-binding globulin. J Clin Invest. 1956 Jan;35(1):44–56. doi: 10.1172/JCI103251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. JARNUM S., LASSEN N. A. Albumin and transferrin metabolism in infectious and toxic diseases. Scand J Clin Lab Invest. 1961;13:357–368. [PubMed] [Google Scholar]
  10. JARNUM S., SCHWARTZ M. [Studies of albumin catabolism by means of I-131-labelled albumin. Methods of calculating the albumin turnover and some fields of clinical application]. Nord Med. 1960 Jun 9;63:708–715. [PubMed] [Google Scholar]
  11. KAITZ A. L. Albumin metabolism in nephrotic adults. J Lab Clin Med. 1959 Feb;53(2):186–194. [PubMed] [Google Scholar]
  12. KATZ J. H. Iron and protein kinetics studied by means of doubly labeled human crystalline transferrin. J Clin Invest. 1961 Dec;40:2143–2152. doi: 10.1172/JCI104440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. MCFARLANE A. S., IRONS L., KOJ A., REGOECZI E. THE MEASUREMENT OF SYNTHESIS RATES OF ALBUMIN AND FIBRINOGEN IN RABBITS. Biochem J. 1965 May;95:536–540. doi: 10.1042/bj0950536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. MCFARLANE A. S. MEASUREMENT OF SYNTHESIS RATES OF LIVER-PRODUCED PLASMA PROTEINS. Biochem J. 1963 Nov;89:277–290. doi: 10.1042/bj0890277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. MCFARLANE A. S., TODD D., CROMWELL S. FIBRINOGEN CATABOLISM IN HUMANS. Clin Sci. 1964 Jun;26:415–420. [PubMed] [Google Scholar]
  17. MILLER L. L., BALE W. F. Synthesis of all plasma protein fractions except gamma globulins by the liver; the use of zone electrophoresis and lysine-epsilon-C14 to define the plasma proteins synthesized by the isolated perfused liver. J Exp Med. 1954 Feb;99(2):125–132. doi: 10.1084/jem.99.2.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McFARLANE A. S. Efficient trace-labelling of proteins with iodine. Nature. 1958 Jul 5;182(4627):53–53. doi: 10.1038/182053a0. [DOI] [PubMed] [Google Scholar]
  19. NAGLER A. L., KOCHWA S., WASSERMAN L. R. Improved isolation of purified siderophilin from individual sera. Proc Soc Exp Biol Med. 1962 Dec;111:746–749. doi: 10.3181/00379727-111-27910. [DOI] [PubMed] [Google Scholar]
  20. PEARSON J. D., VEALL N., VETTER H. A practical method for plasma albumin turnover studies. Strahlentherapie. 1958;107(SONDERBD):290–297. [PubMed] [Google Scholar]
  21. RATNOFF O. D., MENZIE C. A new method for the determination of fibrinogen in small samples of plasma. J Lab Clin Med. 1951 Feb;37(2):316–320. [PubMed] [Google Scholar]
  22. REEVE E. B., PEARSON J. R., MARTZ D. C. Plasma protein synthesis in the liver: method for measurement of albumin formation in vivo. Science. 1963 Mar 8;139(3558):914–916. doi: 10.1126/science.139.3558.914. [DOI] [PubMed] [Google Scholar]
  23. RUTSTEIN D. D., INGENITO E. F., REYNOLDS W. E. The determination of albumin in human blood plasma and serum; a method based on the interaction of albumin with an anionic dye-2(4'-hydroxybenzeneazo) benzoic acid. J Clin Invest. 1954 Feb;33(2):211–221. doi: 10.1172/JCI102887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. STEINFELD J. L. Difference in daily albumin synthesis between normal men and women as measured with II31-labeled albumin. J Lab Clin Med. 1960 Jun;55:904–911. [PubMed] [Google Scholar]
  25. STERLING K. The turnover rate of serum albumin in man as measured by I131-tagged albumin. J Clin Invest. 1951 Nov;30(11):1228–1237. doi: 10.1172/JCI102542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. SWICK R. W. Measurement of protein turnover in rat liver. J Biol Chem. 1958 Apr;231(2):751–764. [PubMed] [Google Scholar]
  27. TAKEDA Y., REEVE E. B. Studies of the metabolism and distribution of albumin with autologous I131-albumin in healthy men. J Lab Clin Med. 1963 Feb;61:183–202. [PubMed] [Google Scholar]
  28. Takeda Y. Studies of the metabolism and distribution of fibrinogen in healthy men with autologous 125-I-labeled fibrinogen. J Clin Invest. 1966 Jan;45(1):103–111. doi: 10.1172/JCI105314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. WALDMANN T. A. Gastrointestinal protein loss demonstrated by Cr-51-labelled albumin. Lancet. 1961 Jul 15;2(7194):121–123. doi: 10.1016/s0140-6736(61)92646-0. [DOI] [PubMed] [Google Scholar]
  30. WALDMANN T. A., STEINFELD J. L., DUTCHER T. F., DAVIDSON J. D., GORDON R. S., Jr The role of the gastrointestinal system in "idiopathic hypoproteinemia". Gastroenterology. 1961 Sep;41:197–207. [PubMed] [Google Scholar]
  31. WEISSMAN S., TSCHUDY D. P., BACCHUS H., EUBANKS M. Use of precursor product relationships in determining serum albumin half-life. J Lab Clin Med. 1961 Jan;57:136–146. [PubMed] [Google Scholar]
  32. WILKINSON P., MENDENHALL C. L. SERUM ALBUMIN TURNOVER IN NORMAL SUBJECTS AND PATIENTS WITH CIRRHOSIS MEASURED BY 131I-LABELLED HUMAN ALBUMIN. Clin Sci. 1963 Oct;25:281–292. [PubMed] [Google Scholar]
  33. WOELLER F. H. Liquid scintillation counting of C-14-labelled CO2 with phenethylamine. Anal Biochem. 1961 Oct;2:508–511. doi: 10.1016/0003-2697(61)90056-2. [DOI] [PubMed] [Google Scholar]
  34. Weissman S. M., Wochner R. D., Mullins F. X., Wynngate A., Waldmann T. A. Synthesis of plasma proteins by hepatectomized dogs. Am J Physiol. 1966 Jan;210(1):128–132. doi: 10.1152/ajplegacy.1966.210.1.128. [DOI] [PubMed] [Google Scholar]

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

RESOURCES