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Originally published In Press as doi:10.1074/jbc.C200267200 on July 1, 2002

J. Biol. Chem., Vol. 277, Issue 34, 30425-30428, August 23, 2002
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ACCELERATED PUBLICATION
Homocysteine Is a Protein Amino Acid in Humans
IMPLICATIONS FOR HOMOCYSTEINE-LINKED DISEASE*

Hieronim JakubowskiDagger

From the Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School, International Center for Public Health, Newark, New Jersey 07101 and the Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznan, Poland

Homocysteine is thought to be a non-protein amino acid. However, in vitro studies suggest that homocysteine is likely to be incorporated by indirect mechanisms into proteins in living organisms. Here I show that homocysteine is a protein amino acid in humans. Homocysteine bound by amide or peptide linkages (Hcy-N-protein) is present in human hemoglobin, serum albumin, and gamma -globulins. 1 molecule of homocysteine per 1000 or 1670 molecules of methionine was present in hemoglobin or albumin, respectively. Other proteins, such as low density lipoprotein, high density lipoprotein, transferrin, antitrypsin, and fibrinogen, contained lower amounts of Hcy-N-protein. In human plasma, levels of Hcy-N-protein represented from 0.3 to 23% of total homocysteine. Thus, Hcy-N-protein is a significant component of homocysteine metabolism in humans, possibly contributing to adverse effects of homocysteine on human cells.


* This research was supported by grants from the National Science Foundation, the American Heart Association, and the Foundation of UMDNJ.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

This paper is dedicated to Professor Jerzy Pawełkiewicz on the occasion of his 80th birthday.

Dagger To whom correspondence should be addressed. Tel.: 973-972-8733; Fax: 973-972-8982; E-mail: jakubows@umdnj.edu.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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