| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA
1Correspondence: Department of Microbiology & Molecular Genetics, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103. E-mail: jakubows{at}umdnj.edu
Homocysteine thiolactone, a cyclic thioester, is synthesized by certain aminoacyl-tRNA synthetases in editing or proofreading reactions that prevent translational incorporation of homocysteine into proteins. Although homocysteine thiolactone is expected to acylate amino groups in proteins, virtually nothing is known regarding reactivity of the thiolactone. Here it is shown that reactions of the thiolactone with protein lysine residues were robust under physiological conditions. In human serum incubated with homocysteine thiolactone, protein homocysteinylation was a major reaction that could be observed with as little as 10 nM thiolactone. Individual proteins were homocysteinylated at rates proportional to their lysine contents. Homocysteinylation led to protein damage, manifested as multimerization and precipitation of extensively modified proteins. Model enzymes, such as methionyl-tRNA synthetase and trypsin, were inactivated by homocysteinylation. Metabolic conversion of homocysteine to the thiolactone, protein homocysteinylation, and resulting protein damage may underlie involvement of Hcy in the pathology of vascular disease.—Jakubowski, H. Protein homocysteinylation: possible mechanism underlying pathological consequences of elevated homocysteine levels.
Key Words: homocysteine thiolactone • atherosclerosis
This article has been cited by other articles:
|
|
 |
|
  M. A. Medina Hyperhomocysteinemia and Occlusive Vascular Disease: An Emergent Role for Fibroblast Growth Factor 2 Circ. Res., April 25, 2008; 102(8): 869 - 870. [Full Text] [PDF]
|
|
|
|
 |
|
 Wei Hsi Chen, Hung Sheng Lin, Yi Fen Kao, Min Yu Lan, and Jia Shou Liu Hyperhomocysteinemia Relates to the Subtype of Antiphospholipid Antibodies in Non-SLE Patients Clinical and Applied Thrombosis/Hemostasis, October 1, 2007; 13(4): 398 - 403. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Undas, M. Kolarz, G. Kopec, R. Glowacki, E. Placzkiewicz-Jankowska, and W. Tracz Autoantibodies against N-homocysteinylated proteins in patients on long-term haemodialysis Nephrol. Dial. Transplant., June 1, 2007; 22(6): 1685 - 1689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Chwatko, G. H. J. Boers, K. A. Strauss, D. M. Shih, and H. Jakubowski Mutations in methylenetetrahydrofolate reductase or cystathionine {beta}-syntase gene, or a high-methionine diet, increase homocysteine thiolactone levels in humans and mice FASEB J, June 1, 2007; 21(8): 1707 - 1713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zinellu, E. Zinellu, S. Sotgia, M. Formato, G. M. Cherchi, L. Deiana, and C. Carru Factors Affecting S-Homocysteinylation of LDL Apoprotein B Clin. Chem., November 1, 2006; 52(11): 2054 - 2059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zimny, M. Sikora, A. Guranowski, and H. Jakubowski Protective Mechanisms against Homocysteine Toxicity: THE ROLE OF BLEOMYCIN HYDROLASE J. Biol. Chem., August 11, 2006; 281(32): 22485 - 22492. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Fraser, N. L. Tuite, A. Bhagwat, and C. P. O'Byrne Global effects of homocysteine on transcription in Escherichia coli: induction of the gene for the major cold-shock protein, CspA. Microbiology, August 1, 2006; 152(Pt 8): 2221 - 2231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Undas, J. Brozek, M. Jankowski, Z. Siudak, A. Szczeklik, and H. Jakubowski Plasma Homocysteine Affects Fibrin Clot Permeability and Resistance to Lysis in Human Subjects Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1397 - 1404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Jakubowski Pathophysiological Consequences of Homocysteine Excess J. Nutr., June 1, 2006; 136(6): 1741S - 1749S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. S. Carlson, P. J. Heagerty, T. S. Hatsukami, R. J. Richter, J. Ranchalis, J. Lewis, T. J. Bacus, L. A. McKinstry, G. D. Schellenberg, M. Rieder, et al. TagSNP analyses of the PON gene cluster: effects on PON1 activity, LDL oxidative susceptibility, and vascular disease J. Lipid Res., May 1, 2006; 47(5): 1014 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. L. Tuite, K. R. Fraser, and C. P. O'Byrne Homocysteine Toxicity in Escherichia coli Is Caused by a Perturbation of Branched-Chain Amino Acid Biosynthesis J. Bacteriol., July 1, 2005; 187(13): 4362 - 4371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bosch-Marce, R. Pola, A. B Wecker, M. Silver, A. Weber, C. Luedemann, C. Curry, T. Murayama, M. Kearney, Y.-s. Yoon, et al. Hyperhomocyst(e)inemia impairs angiogenesis in a murine model of limb ischemia Vascular Medicine, February 1, 2005; 10(1): 15 - 22. [Abstract] [PDF]
|
|
|
|
|
|
G. Chwatko and H. Jakubowski Urinary Excretion of Homocysteine-Thiolactone in Humans Clin. Chem., February 1, 2005; 51(2): 408 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Vignini, L. Nanetti, T. Bacchetti, G. Ferretti, G. Curatola, and L. Mazzanti Modification Induced by Homocysteine and Low-Density Lipoprotein on Human Aortic Endothelial Cells: An In Vitro Study J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4558 - 4561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Undas, J. Perla, M. Lacinski, W. Trzeciak, R. Kazmierski, and H. Jakubowski Autoantibodies Against N-Homocysteinylated Proteins in Humans: Implications for Atherosclerosis Stroke, June 1, 2004; 35(6): 1299 - 1304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Glowacki and H. Jakubowski Cross-talk between Cys34 and Lysine Residues in Human Serum Albumin Revealed by N-Homocysteinylation J. Biol. Chem., March 19, 2004; 279(12): 10864 - 10871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Gouedard, N. Koum-Besson, R. Barouki, and Y. Morel Opposite Regulation of the Human Paraoxonase-1 Gene PON-1 by Fenofibrate and Statins Mol. Pharmacol., April 1, 2003; 63(4): 945 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jakubowski and A. Guranowski Metabolism of Homocysteine-thiolactone in Plants J. Biol. Chem., February 21, 2003; 278(9): 6765 - 6770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jakubowski Homocysteine Is a Protein Amino Acid in Humans. IMPLICATIONS FOR HOMOCYSTEINE-LINKED DISEASE J. Biol. Chem., August 16, 2002; 277(34): 30425 - 30428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Hill, R. Mecham, and B. Starcher Fibrillin-2 Defects Impair Elastic Fiber Assembly in a Homocysteinemic Chick Model J. Nutr., August 1, 2002; 132(8): 2143 - 2150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. RAGONE Homocystine solubility and vascular disease FASEB J, March 1, 2002; 16(3): 401 - 404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jakubowski Translational Accuracy of Aminoacyl-tRNA Synthetases: Implications for Atherosclerosis J. Nutr., November 1, 2001; 131(11): 2983S - 2987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jakubowski, L. Zhang, A. Bardeguez, and A. Aviv Homocysteine Thiolactone and Protein Homocysteinylation in Human Endothelial Cells : Implications for Atherosclerosis Circ. Res., July 7, 2000; 87(1): 45 - 51. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
H. Jakubowski Calcium-dependent Human Serum Homocysteine Thiolactone Hydrolase. A PROTECTIVE MECHANISM AGAINST PROTEIN N-HOMOCYSTEINYLATION J. Biol. Chem., February 11, 2000; 275(6): 3957 - 3962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jakubowski Homocysteine Thiolactone: Metabolic Origin and Protein Homocysteinylation in Humans J. Nutr., February 1, 2000; 130(2): 377 - 377. [Abstract] [Full Text]
|
|
|
|
|
|
H. Jakubowski Translational Incorporation of S-Nitrosohomocysteine into Protein J. Biol. Chem., July 14, 2000; 275(29): 21813 - 21816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
