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A more recent version of this article appeared on August 16, 2002
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Papers In Press, published online ahead of print July 1, 2002
J. Biol. Chem, 10.1074/jbc.C200267200
Submitted on May 3, 2002
Revised on June 25, 2002
Accepted on July 1, 2002

Homocysteine is a protein amino acid in humans: Implications for homocysteine-linked disease

Hieronim Jakubowski

Microbiology & Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, NJ 07101-1709

Corresponding Author: jakubows{at}umdnj.edu

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 g-globulins. One 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, anti-trypsin, 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 Hcy metabolism in humans, possibly contributing to adverse effects of Hcy on human cells.


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