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Clinical Chemistry, Vol 31, 624-628, Copyright © 1985 by American Association for Clinical Chemistry
H Refsum, S Helland and PM Ueland
Using a modification of the radioenzymic assay described previously (J Biol Chem 259: 2360-2364, 1984) we measured homocysteine in freshly prepared plasma and urine from volunteers. The concentration of free homocysteine--i.e., the amount measurable in plasma after deproteinization by strong acid--was 2.27 (SEM 0.11) mumol/L for 18 men and 1.95 (SEM 0.13) mumol/L for 16 women (p greater than 0.05, not significant). About 70% of the total homocysteine in human plasma was associated with plasma proteins, and was precipitated with strong acid. The concentration of protein-bound homocysteine in plasma was 6.51 (SEM 0.32) mumol/L for men and 7.29 (SEM 0.65) mumol/L for women, a significantly (p less than 0.01) different spread. Homocysteine was rapidly released from plasma proteins in the presence of a reducing agent, dithioerythritol. By gel filtration of plasma on a "high- performance" liquid-chromatographic column, albumin was shown to be the sole carrier of homocysteine in plasma. Because the fraction bound to protein as determined by this procedure equaled that obtained by precipitation of plasma proteins with acid, we conclude that homocysteine is bound to albumin in vivo. The concentration of homocysteine in urine ranged from 3.5 to 9.5 mumol/L, about 6 mumol of homocysteine being excreted per 24 h.
The following articles in journals at HighWire Press have cited this article:
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  S. M. Colgan and R. C. Austin Homocysteinylation of Metallothionein Impairs Intracellular Redox Homeostasis: The Enemy Within! Arterioscler. Thromb. Vasc. Biol., January 1, 2007; 27(1): 8 - 11. [Full Text] [PDF]
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 R. Fux, D. Kloor, M. Hermes, T. Rock, B. Proksch, A. Grenz, U. Delabar, R. Bucheler, S. Igel, K. Morike, et al. Effect of acute hyperhomocysteinemia on methylation potential of erythrocytes and on DNA methylation of lymphocytes in healthy male volunteers Am J Physiol Renal Physiol, October 1, 2005; 289(4): F786 - F792. [Abstract] [Full Text] [PDF]
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 W. Herrmann, H. Schorr, R. Obeid, J. Makowski, B. Fowler, and M. K. Kuhlmann Disturbed Homocysteine and Methionine Cycle Intermediates S-Adenosylhomocysteine and S-Adenosylmethionine Are Related to Degree of Renal Insufficiency in Type 2 Diabetes Clin. Chem., May 1, 2005; 51(5): 891 - 897. [Abstract] [Full Text] [PDF]
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 R. G. V. Smolders, K. de Meer, P. Kenemans, C. Jakobs, W. Kulik, and M. J. van der Mooren Oral Estradiol Decreases Plasma Homocysteine, Vitamin B6, and Albumin in Postmenopausal Women But Does Not Change the Whole-Body Homocysteine Remethylation and Transmethylation Flux J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2218 - 2224. [Abstract] [Full Text] [PDF]
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R. Rej Clinical Chemistry through Clinical Chemistry: A Journal Timeline Clin. Chem., December 1, 2004; 50(12): 2415 - 2458. [Abstract] [Full Text] [PDF]
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F. Stam, C. van Guldener, P. M. ter Wee, W. Kulik, D. E. C. Smith, C. Jakobs, C. D. A. Stehouwer, and K. de Meer Homocysteine clearance and methylation flux rates in health and end-stage renal disease: association with S-adenosylhomocysteine Am J Physiol Renal Physiol, August 1, 2004; 287(2): F215 - F223. [Abstract] [Full Text] [PDF]
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H. Refsum, A. D. Smith, P. M. Ueland, E. Nexo, R. Clarke, J. McPartlin, C. Johnston, F. Engbaek, J. Schneede, C. McPartlin, et al. Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion Clin. Chem., January 1, 2004; 50(1): 3 - 32. [Abstract] [Full Text] [PDF]
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 A. Lim, S. Sengupta, M. E. McComb, R. Theberge, W. G. Wilson, C. E. Costello, and D. W. Jacobsen In Vitro and in Vivo Interactions of Homocysteine with Human Plasma Transthyretin J. Biol. Chem., December 12, 2003; 278(50): 49707 - 49713. [Abstract] [Full Text] [PDF]
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D. H. Krieter and B. Canaud High permeability of dialysis membranes: what is the limit of albumin loss? Nephrol. Dial. Transplant., April 1, 2003; 18(4): 651 - 654. [Full Text] [PDF]
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N. Q. Hanson, J. H. Eckfeldt, K. Schwichtenberg, O. Aras, and M. Y. Tsai Interlaboratory Variation of Plasma Total Homocysteine Measurements: Results of Three Successive Homocysteine Proficiency Testing Surveys Clin. Chem., September 1, 2002; 48(9): 1539 - 1545. [Abstract] [Full Text] [PDF]
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A. K. Majors, S. Sengupta, B. Willard, M. T. Kinter, R. E. Pyeritz, and D. W. Jacobsen Homocysteine Binds to Human Plasma Fibronectin and Inhibits Its Interaction With Fibrin Arterioscler. Thromb. Vasc. Biol., August 1, 2002; 22(8): 1354 - 1359. [Abstract] [Full Text] [PDF]
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 C.-J. Hung, P.-C. Huang, S.-C. Lu, Y.-H. Li, H.-B. Huang, B.-F. Lin, S.-J. Chang, and H.-F. Chou Plasma Homocysteine Levels in Taiwanese Vegetarians Are Higher than Those of Omnivores J. Nutr., February 1, 2002; 132(2): 152 - 158. [Abstract] [Full Text] [PDF]
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S. Sengupta, C. Wehbe, A. K. Majors, M. E. Ketterer, P. M. DiBello, and D. W. Jacobsen Relative Roles of Albumin and Ceruloplasmin in the Formation of Homocystine, Homocysteine-Cysteine-mixed Disulfide, and Cystine in Circulation J. Biol. Chem., December 7, 2001; 276(50): 46896 - 46904. [Abstract] [Full Text] [PDF]
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 A. N. FRIEDMAN, A. G. BOSTOM, J. SELHUB, A. S. LEVEY, and I. H. ROSENBERG The Kidney and Homocysteine Metabolism J. Am. Soc. Nephrol., October 1, 2001; 12(10): 2181 - 2189. [Abstract] [Full Text] [PDF]
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B. G. Nedrebo, O. Nygard, P. M. Ueland, and E. A. Lien Plasma Total Homocysteine in Hyper- and Hypothyroid Patients before and during 12 Months of Treatment Clin. Chem., September 1, 2001; 47(9): 1738 - 1741. [Full Text] [PDF]
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R. H. Williams, J. A. Maggiore, R. D. Reynolds, and C. M. Helgason Novel Approach for the Determination of the Redox Status of Homocysteine and Other Aminothiols in Plasma from Healthy Subjects and Patients with Ischemic Stroke Clin. Chem., June 1, 2001; 47(6): 1031 - 1039. [Abstract] [Full Text] [PDF]
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E. Nexo, F. Engbaek, P. M. Ueland, C. Westby, P. O'Gorman, C. Johnston, B. F. Kase, A. B. Guttormsen, I. Alfheim, J. McPartlin, et al. Evaluation of Novel Assays in Clinical Chemistry: Quantification of Plasma Total Homocysteine Clin. Chem., August 1, 2000; 46(8): 1150 - 1156. [Abstract] [Full Text] [PDF]
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S. H. Mudd, J. D. Finkelstein, H. Refsum, P. M. Ueland, M. R. Malinow, S. R. Lentz, D. W. Jacobsen, L. Brattstrom, B. Wilcken, D. E. L. Wilcken, et al. Homocysteine and Its Disulfide Derivatives : A Suggested Consensus Terminology Arterioscler. Thromb. Vasc. Biol., July 1, 2000; 20(7): 1704 - 1706. [Full Text] [PDF]
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P. Jungers, D. Joly, Z. Massy, P. Chauveau, A.-T. Nguyen, J. Aupetit, and B. Chadefaux Sustained reduction of hyperhomocysteinaemia with folic acid supplementation in predialysis patients Nephrol. Dial. Transplant., December 1, 1999; 14(12): 2903 - 2906. [Abstract] [Full Text] [PDF]
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K. Rasmussen, J. Moller, and M. Lyngbak Within-Person Variation of Plasma Homocysteine and Effects of Posture and Tourniquet Application Clin. Chem., October 1, 1999; 45(10): 1850 - 1855. [Abstract] [Full Text] [PDF]
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J. Moller, K. Rasmussen, and L. Christensen External Quality Assessment of Methylmalonic Acid and Total Homocysteine Clin. Chem., September 1, 1999; 45(9): 1536 - 1542. [Abstract] [Full Text] [PDF]
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 M. F. Lawson, C. van Guldener, A. J.M. Donker, C. D.A. Stehouwer, K. A. Nath, G. N. Welch, and J. Loscalzo Homocyst(e)ine and Atherothrombosis N. Engl. J. Med., August 13, 1998; 339(7): 477 - 479. [Full Text]
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D. W. Jacobsen Homocysteine and vitamins in cardiovascular disease Clin. Chem., August 1, 1998; 44(8): 1833 - 1843. [Abstract] [Full Text] [PDF]
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 J. Danesh, R. Collins, P. Appleby, and R. Peto Association of Fibrinogen, C-reactive Protein, Albumin, or Leukocyte Count With Coronary Heart Disease: Meta-analyses of Prospective Studies JAMA, May 13, 1998; 279(18): 1477 - 1482. [Abstract] [Full Text] [PDF]
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A. Pastore, R. Massoud, C. Motti, A. L. Russo, G. Fucci, C. Cortese, and G. Federici Fully automated assay for total homocysteine, cysteine, cysteinylglycine, glutathione, cysteamine, and 2-mercaptopropionylglycine in plasma and urine Clin. Chem., April 1, 1998; 44(4): 825 - 832. [Abstract] [Full Text] [PDF]
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E. J. Giltay, E. K. Hoogeveen, J. M. H. Elbers, L. J. G. Gooren, H. Asscheman, and C. D. A. Stehouwer Effects of Sex Steroids on Plasma Total Homocysteine Levels: A Study in Transsexual Males and Females J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 550 - 553. [Abstract] [Full Text]
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F. Frantzen, A. L. Faaren, I. Alfheim, and A. K. Nordhei Enzyme conversion immunoassay for determining total homocysteine in plasma or serum Clin. Chem., February 1, 1998; 44(2): 311 - 316. [Abstract] [Full Text] [PDF]
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M. A. Mansoor, C. Bergmark, A. M. Svardal, P. E. Lonning, and P. M. Ueland Redox Status and Protein Binding of Plasma Homocysteine and Other Aminothiols in Patients With Early-Onset Peripheral Vascular Disease : Homocysteine and Peripheral Vascular Disease Arterioscler. Thromb. Vasc. Biol., February 1, 1995; 15(2): 232 - 240. [Abstract] [Full Text]
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S. Sengupta, H. Chen, T. Togawa, P. M. DiBello, A. K. Majors, B. Budy, M. E. Ketterer, and D. W. Jacobsen Albumin Thiolate Anion Is an Intermediate in the Formation of Albumin-S-S-Homocysteine J. Biol. Chem., August 3, 2001; 276(32): 30111 - 30117. [Abstract] [Full Text] [PDF]
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