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Genomes and Genes | Hieronim JakubowskiSummaryAffiliation: New Jersey Country: USA Publications
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Publications
Protective mechanisms against homocysteine toxicity: the role of bleomycin hydrolaseJaroslaw Zimny
Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey New Jersey Medical School, International Center for Public Health, Newark, New Jersey 07101, USA
J Biol Chem 281:22485-92. 2006..Our data suggest that BLH protects cells against Hcy toxicity by hydrolyzing intracellular Hcy-thiolactone...
Quality control in tRNA chargingHieronim Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark, NJ, USA
Wiley Interdiscip Rev RNA 3:295-310. 2012..Elevated levels of mistranslation and the synthesis of statistical proteins can be beneficial for pathogens by increasing phenotypic variation essential for the evasion of host defenses...
Metabolism of homocysteine thiolactone in human cell cultures. Possible mechanism for pathological consequences of elevated homocysteine levelsH Jakubowski
Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey New Jersey Medical School, Newark, New Jersey 07103, USA
J Biol Chem 272:1935-42. 1997..The metabolic conversion of homocysteine to homocysteine thiolactone and the reactivity of the thiolactone toward proteins may explain pathological consequences of elevated levels of homocysteine such as observed in vascular disease...
Molecular basis of homocysteine toxicity in humansH Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, 225 Warren Street, Newark, New Jersey 07101, USA
Cell Mol Life Sci 61:470-87. 2004..The ability of Hcy to interfere with protein biosynthesis, which causes protein damage, induces cell death and elicits immune response, is likely to contribute to the pathology of human disease...
Genetic or nutritional disorders in homocysteine or folate metabolism increase protein N-homocysteinylation in miceHieronim Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, 225 Warren St, Newark, NJ 07101 1709, USA
FASEB J 23:1721-7. 2009..These findings provide evidence that N-Hcy-protein is an important metabolite associated with Hcy pathophysiology in the mouse...
Mutations in cystathionine beta-synthase or methylenetetrahydrofolate reductase gene increase N-homocysteinylated protein levels in humansHieronim Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, 225 Warren St, Newark, NJ 07101 1709, USA
FASEB J 22:4071-6. 2008..We also show that CBS-deficient patients have significantly elevated plasma levels of prothrombotic N-Hcy-fibrinogen. These results provide a possible explanation for increased atherothrombosis observed in CBS-deficient patients...
New method for the determination of protein N-linked homocysteineHieronim Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark, NJ 07101, USA
Anal Biochem 380:257-61. 2008..0127-0.0828 vs. 0.0027-0.0086 mol/mol). Normal human plasma and milk were found to contain submicromolar concentrations of protein N-linked Hcy, whereas cow milk and whey contained micromolar concentrations of protein N-linked Hcy...
The molecular basis of homocysteine thiolactone-mediated vascular diseaseHieronim Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark, NJ 07101 1709, USA
Clin Chem Lab Med 45:1704-16. 2007..This article reviews recent evidence supporting the hypothesis that Hcy-thiolactone contributes to pathophysiological effects of Hcy on the vascular system...
Facile syntheses of [35S]homocysteine-thiolactone, [35S]homocystine, [35S]homocysteine, and [S-nitroso-35S]homocysteineHieronim Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark, NJ 07101, USA
Anal Biochem 370:124-6. 2007
The role of paraoxonase 1 in the detoxification of homocysteine thiolactoneHieronim Jakubowski
Department of Biochemistry and Biotechnology, University of Life Sciences, Poznan, Poland
Adv Exp Med Biol 660:113-27. 2010..This article outlines Hcy-thiolactone pathobiology and reviews evidence documenting the role of PON1 in minimizing Hcy-thiolactone and N-Hcy-protein accumulation...
Anti-N-homocysteinylated protein autoantibodies and cardiovascular diseaseHieronim Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark, NJ 07101 1709, USA
Clin Chem Lab Med 43:1011-4. 2005....
Chemical biology of homocysteine thiolactone and related metabolitesHieronim Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark, New Jersey, USA
Adv Clin Chem 55:81-103. 2011..This chapter reviews fundamental biological chemistry of Hcy-thiolactone, N-Hcy-protein, and N epsilon-Hcy-Lys and discusses their clinical significance...
Pathophysiological consequences of homocysteine excessHieronim Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark, NJ 07101, USA
J Nutr 136:1741S-1749S. 2006..Potential utility of Hcy-thiolactone, N-Hcy-protein, or anti-N-Hcy-protein autoantibodies as markers of Hcy excess is discussed...
Mechanism of the condensation of homocysteine thiolactone with aldehydesHieronim Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey, Medical School, Newark, NJ 07101, USA
Chemistry 12:8039-43. 2006..The facile formation of tetrahydrothiazines may contribute to HTL elimination from the human body...
The pathophysiological hypothesis of homocysteine thiolactone-mediated vascular diseaseH Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark, NJ 07101, USA
J Physiol Pharmacol 59:155-67. 2008..We conclude that genetic or dietary hyperhomocysteinemia significantly elevates proatherothrombotic metabolites Hcy-thiolactone and N-Hcy-proteins in humans and mice...
Homocysteine-thiolactone and S-nitroso-homocysteine mediate incorporation of homocysteine into protein in humansHieronim Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark 07101 1709, USA
Clin Chem Lab Med 41:1462-6. 2003..Hcy-thiolactone is present in human plasma. Modification with Hcy-thiolactone leads to protein damage. Hcy-thiolactone is detoxified by Hcy-thiolactonase/paraoxonase present in a subset of high-density lipoprotein particles in humans...
Metabolism of homocysteine-thiolactone in plantsHieronim Jakubowski
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, USA
J Biol Chem 278:6765-70. 2003..Thus, Hcy-thiolactone and Hcy bound to protein by an amide (or peptide) linkage (Hcy-N-protein) are significant components of plant Hcy metabolism...
Aminoacyl thioester chemistry of class II aminoacyl-tRNA synthetasesH Jakubowski
Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey New Jersey Medical School, 185 South Orange Avenue, Newark, New Jersey 07103, USA
Biochemistry 36:11077-85. 1997..That the thiol-binding subsite exists also in AspRS and SerRS, which do not need editing function, suggests that these class II enzymes possess vestigial editing functions...
Aminoacylation of coenzyme A and pantetheine by aminoacyl-tRNA synthetases: possible link between noncoded and coded peptide synthesisH Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, 185 South Orange Avenue, Newark, New Jersey 07103, USA
Biochemistry 37:5147-53. 1998....
Misacylation of tRNALys with noncognate amino acids by lysyl-tRNA synthetaseH Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, Newark 07103, USA
Biochemistry 38:8088-93. 1999..A novel feature of this editing reaction is that ornithine lactam is formed by the facile cyclization of ornithyl adenylate...
Protein homocysteinylation: possible mechanism underlying pathological consequences of elevated homocysteine levelsH Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, Newark, NJ 07103, USA
FASEB J 13:2277-83. 1999..Jakubowski, H. Protein homocysteinylation: possible mechanism underlying pathological consequences of elevated homocysteine levels...
Calcium-dependent human serum homocysteine thiolactone hydrolase. A protective mechanism against protein N-homocysteinylationH Jakubowski
Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA
J Biol Chem 275:3957-62. 2000..By detoxifying homocysteine thiolactone, the thiolactonase/paraoxonase would protect proteins against homocysteinylation, a potential contributing factor to atherosclerosis...
Translational incorporation of S-nitrosohomocysteine into proteinH Jakubowski
Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA
J Biol Chem 275:21813-6. 2000..S-Nitrosylation-mediated translational incorporation of Hcy into protein may occur under natural conditions in cells and contribute to Hcy-induced pathogenesis in atherosclerosis...
Homocysteine thiolactone and protein homocysteinylation in human endothelial cells: implications for atherosclerosisH Jakubowski
Department of Microbiology, UMDNJ New Jersey Medical School, Newark, NJ, USA
Circ Res 87:45-51. 2000..These data support a hypothesis that metabolic conversion of homocysteine to thiolactone and protein homocysteinylation by thiolactone may play a role in homocysteine-induced vascular damage...
Genetic determinants of homocysteine thiolactonase activity in humans: implications for atherosclerosisH Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA
FEBS Lett 491:35-9. 2001..High thiolactonase activity afforded better protection against protein homocysteinylation than low thiolactonase activity. These results suggest that variations in HTase may play a role in Hcy-associated cardiovascular disease...
Protein N-homocysteinylation: implications for atherosclerosisH Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, Newark 07103, USA
Biomed Pharmacother 55:443-7. 2001..Variations in Hcy thiolactonase may play an important role in Hcy-associated human cardiovascular disease...
Translational accuracy of aminoacyl-tRNA synthetases: implications for atherosclerosisH Jakubowski
Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103, USA
J Nutr 131:2983S-7S. 2001....
Homocysteine is a protein amino acid in humans. Implications for homocysteine-linked diseaseHieronim Jakubowski
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, NJ 07101, USA
J Biol Chem 277:30425-8. 2002..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...
The determination of homocysteine-thiolactone in biological samplesHieronim Jakubowski
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark 07101, USA
Anal Biochem 308:112-9. 2002..The data support the conclusion that homocysteine-thiolactone is a ubiquitous metabolite whose levels are directly related to homocysteine levels...
Quality control in tRNA charging -- editing of homocysteineHieronim Jakubowski
UMDNJ New Jersey Medical School, Department of Microbiology and Molecular Genetics, International Center for Public Health, Newark, USA
Acta Biochim Pol 58:149-63. 2011..Excessive homocysteine thiolactone synthesis in hyperhomocysteinemia caused by genetic or nutritional deficiencies is linked to human vascular and neurological diseases...
Mutations in methylenetetrahydrofolate reductase or cystathionine beta-synthase gene, or a high-methionine diet, increase homocysteine thiolactone levels in humans and miceGrazyna Chwatko
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, 225 Warren St, Newark, NJ 07101 1709, USA
FASEB J 21:1707-13. 2007..7-fold and 25-fold increases in plasma and urinary Hcy-thiolactone levels, respectively. Thus, we conclude that hyperhomocysteinemia leads to significant increases in the atherogenic metabolite Hcy-thiolactone in humans and mice...
Immunohistochemical detection of N-homocysteinylated proteins in humans and miceJoanna Perła-Kaján
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland
Biomed Pharmacother 62:473-9. 2008..In conclusion, polyclonal rabbit anti-N-Hcy-protein antibody can detect and monitor N-homocysteinylated proteins in human and mouse tissues with good sensitivity and specificity...
Metabolism and neurotoxicity of homocysteine thiolactone in mice: evidence for a protective role of paraoxonase 1Kamila Borowczyk
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark, NJ 07101, USA
J Alzheimers Dis 30:225-31. 2012....
Homocysteine editing and growth inhibition in Escherichia coliMarta Sikora
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark, NJ 07101, USA
Microbiology 155:1858-65. 2009..We also show that the levels of protein N-linked Hcy modestly increase in E. coli cells in Hcy-supplemented cultures. The results suggest that Hcy editing restrains bacterial growth...
Metabolism and neurotoxicity of homocysteine thiolactone in mice: protective role of bleomycin hydrolaseKamila Borowczyk
Department of Microbiology and Molecular Genetics, International Center for Public Health, UMDNJ New Jersey Medical School, 225 Warren Street, Newark, NJ 07101, USA
Amino Acids 43:1339-48. 2012....
Paraoxonase 1 and homocysteine metabolismJoanna Perła-Kaján
Department of Biochemistry and Biotechnology, Poznan University of Life Sciences, Poznan, Poland
Amino Acids 43:1405-17. 2012..The links between PON1 and Hcy in relation to pathological states such as coronary artery disease, stroke, diabetic mellitus, kidney failure and Alzheimer's disease that emerge from recent studies are the topics of this review...
Direct monitoring of albumin lysine-525 N-homocysteinylation in human serum by liquid chromatography/mass spectrometryMarta Sikora
Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61 704 Poznan, Poland
Anal Biochem 405:132-4. 2010..Using this method, we found that the extent of lysine-525 N-homocysteinylation was significantly increased in patients with cystathionine beta-synthase deficiency...
Cross-talk between Cys34 and lysine residues in human serum albumin revealed by N-homocysteinylationRafal Glowacki
Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, International Center for Public Health, Newark, New Jersey 07103, USA
J Biol Chem 279:10864-71. 2004....
Paraoxonase 1 protects against protein N-homocysteinylation in humansJoanna Perla-Kajan
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, 225 Warren St Newark, NJ 07101 1709, USA
FASEB J 24:931-6. 2010..Perła-Kaján, J., Jakubowski, H. Paraoxonase 1 protects against protein N-homocysteinylation in humans...
Autoantibodies against N-homocysteinylated proteins in humans: implications for atherosclerosisAnetta Undas
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark, NJ 07101, USA
Stroke 35:1299-304. 2004..CONCLUSIONS: These findings support a hypothesis that Nepsilon-Hcy-Lys-protein is a neoself antigen, which may contribute to immune activation, an important modulator of atherogenesis...
Properties of Escherichia coli EF-Tu mutants designed for fluorescence resonance energy transfer from tRNA moleculesJoanna Perla-Kajan
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, Newark, 07101, USA
Protein Eng Des Sel 23:129-36. 2010..The results indicate that at least three EF-Tu mutants, K324C, G325C and E348C, are suitable for further studies. Remarkably, GST fusions that were not cleaved were also active in the various assays, despite the N-terminal fusion...
Analysis of site-specific N-homocysteinylation of human serum albumin in vitro and in vivo using MALDI-ToF and LC-MS/MS mass spectrometryLukasz Marczak
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12 14, Poznan, Poland
J Proteomics 74:967-74. 2011....
Purification of antibodies against N-homocysteinylated proteins by affinity chromatography on Nomega-homocysteinyl-aminohexyl-AgaroseJoanna Perła
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark, NJ 07101, USA
J Chromatogr B Analyt Technol Biomed Life Sci 807:257-61. 2004..6 and eluted with a pH 2.3 buffer. Enzyme-linked immunosorbent assays demonstrate that the antibody recognizes specifically N-homocysteinylated variants of hemoglobin, albumin, transferrin, and antitrypsin...
The determination of homocysteine-thiolactone in human plasmaGrazyna Chwatko
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark, NJ 07103, USA
Anal Biochem 337:271-7. 2005..82+/-6.13 nM. In 29 of the 60 human plasma samples analyzed, homocysteine-thiolactone levels were below the detection limit. Homocysteine-thiolactone represented from 0 to 0.28%, on average 0.023+/-0.05%, of plasma total homocysteine...
Design and properties of efficient tRNA:EF-Tu FRET system for studies of ribosomal translationMaxim Chudaev
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, Newark, NJ 07101, USA
Protein Eng Des Sel 26:347-57. 2013..The results obtained demonstrate that the EF-Tu:tRNA FRET system described can be used for investigations of ribosomal translation in many types of experiments...
Plasma total homocysteine is a determinant of carotid intima-media thickness and circulating endothelial progenitor cells in patients with newly diagnosed hypertensionPaweł Bogdański
Department of Internal Medicine, Metabolic Disorders and Hypertension, Poznan University of Medical Sciences, Poznan, Poland
Clin Chem Lab Med 50:1107-13. 2012..Our objective was to examine a hypothesis that Hcy is a predictor of total antioxidant status (TAS) and endothelial progenitor cells (EPCs), important in the repair of injured endothelium, in hypertensive patients...
Cation exchange HPLC analysis of desmosines in elastin hydrolysatesJoanna Perła-Kaján
Department of Biochemistry and Biotechnology, Poznan University of Life Sciences, 60 637 Poznan, Poland
Anal Bioanal Chem 401:2473-9. 2011..We also found that desmosines levels were lower in lung elastin isolated from hyperhomocysteinemic Pcft(-/-) mice deficient in intestinal folate transport compared with wild-type Pcft(+/+) animals...
Urinary excretion of homocysteine-thiolactone in humansGrazyna Chwatko
Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, International Center for Public Health, Newark 07103, USA
Clin Chem 51:408-15. 2005..Using these methods we showed that the human body eliminates Hcy-thiolactone by urinary excretion. Our data also suggest that the protonation status of its amino group affects Hcy-thiolactone excretion...
Reduced homocysteine-thiolactonase activity in Alzheimer's diseaseJoanna Suszynska
Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark, NJ 07101 1709, USA
J Alzheimers Dis 19:1177-83. 2010..Levels of brain total Hcy and N-linked protein Hcy did not differ between AD cases and controls. These results suggest that diminished functional BLH activity could contribute to the pathology of AD...
The effects of age and hyperhomocysteinemia on the redox forms of plasma thiolsDanila Di Giuseppe
Department of Neuroscience, Pharmacology Unit, University of Sienna, Sienna, Italy
J Lab Clin Med 144:235-45. 2004....
Antibodies to N-homocysteinylated albumin as a marker for early-onset coronary artery disease in menAnetta Undas
Department of Medicine, Jagiellonian University School of Medicine, 8 Skawinska Street, 31-066 Cracow, Poland
Thromb Haemost 93:346-50. 2005..An autoimmune response to Nepsilon-Hcy-albumin may represent a novel mechanism involved in the early development of CAD...
Synergistic, random sequential binding of substrates in cobalamin-independent methionine synthaseRebecca E Taurog
Department of Biological Chemistry, The University of Michigan, Ann Arbor, Michigan 48109 1055, USA
Biochemistry 45:5083-91. 2006..Methyl transfer has been determined to be slow compared to ternary complex formation and dissociation. Simulations indicate that nearly all of the enzyme is present as the ternary complex under physiological conditions...
Folic acid administration and antibodies against homocysteinylated proteins in subjects with hyperhomocysteinemiaAnetta Undas
Institute of Cardiology, Jagiellonian University of Medicine, Cracow, Poland
Thromb Haemost 96:342-7. 2006..These observations might explain at least in part the failure of vitamin therapy to reduce the risk of cardiovascular events as recently reported...
Modification by homocysteine thiolactone affects redox status of cytochrome CJoanna Perła-Kaján
Institute of Bioorganic Chemistry Polish Academy of Sciences, 61 704 Poznan, Poland
Biochemistry 46:6225-31. 2007..However, no major secondary structure perturbations were observed as shown by circular dichroism spectroscopy. Our data illustrate how N-homocysteinylation can interfere with the function of heme-containing proteins...
Plasma homocysteine affects fibrin clot permeability and resistance to lysis in human subjectsAnetta Undas
Institute of Cardiology, Jagiellonian University School of Medicine, Krakow, Poland
Arterioscler Thromb Vasc Biol 26:1397-404. 2006..Our data are consistent with a mechanism of thrombosis in hyperhomocysteinemia, which involves modification of fibrinogen by Hcy-thiolactone...
Letter by Undas and Jakubowski regarding article, "Relationship between homocysteine and mortality in chronic kidney disease"Anetta Undas
Circulation 114:e547; author reply e548. 2006
Prevention of brain disease from severe 5,10-methylenetetrahydrofolate reductase deficiencyKevin A Strauss
Clinic for Special Children, Strasburg, PA 17579, USA
Mol Genet Metab 91:165-75. 2007..To effectively support the metabolic requirements of rapid brain growth, a large dose of betaine should be started early in life...
[The role of homocysteine thiolactone in some of human diseases]Marta Sikora
Instytut Chemii Bioorganicznej PAN, Poznan
Postepy Biochem 52:417-23. 2006..We also describe the effect of vitamin therapy (folic acid, vitamins: B6, B12) used for lowering the homocysteine level in humans as well...
Differential regulation of homocysteine transport in vascular endothelial and smooth muscle cellsXiaohua Jiang
Temple University School of Medicine, Department of Pharmacology, 3420 North Broad Street, Philadelphia, PA 19140, USA
Arterioscler Thromb Vasc Biol 27:1976-83. 2007..This study characterized and directly compared Hcy transport in cultured human aortic ECs (HAECs) and smooth muscle cells (HASMCs)...
