Mutations in cystathionine beta-synthase or methylenetetrahydrofolate reductase gene increase N-homocysteinylated protein levels in humans

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
H JakubowskiKevin A Strauss

Abstract

Severely elevated plasma homocysteine (Hcy) levels observed in genetic disorders of Hcy metabolism are associated with pathologies in multiple organs and lead to premature death due to vascular complications. In addition to elevating plasma Hcy, mutations in cystathionine beta-synthase (CBS) or methylenetetrahydrofolate reductase (MTHFR) gene lead to markedly elevated levels of circulating Hcy-thiolactone. The thiooester chemistry of Hcy-thiolactone underlies its ability to form isopeptide bonds with protein lysine residues (N-Hcy-protein), which may impair or alter the protein's function. However, it was not known whether genetic deficiencies in Hcy metabolism affect N-Hcy-protein levels in humans. Here we show that plasma N-Hcy-protein levels are significantly elevated in CBS- and MTHFR-deficient patients. 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.

References

Sep 12, 1974·The New England Journal of Medicine·L A HarkerR Ross
Jul 20, 2001·Annals of the New York Academy of Sciences·M Hanss, F Biot
Nov 1, 2001·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·H Jakubowski
Jul 3, 2002·The Journal of Biological Chemistry·Hieronim Jakubowski
Sep 18, 2002·Analytical Biochemistry·Hieronim Jakubowski
May 17, 2003·Birth Defects Research. Part A, Clinical and Molecular Teratology·Carmen Maestro de las CasasJulia Pérez-Miguelsanz
Mar 5, 2004·Cellular and Molecular Life Sciences : CMLS·H Jakubowski
May 8, 2004·Stroke; a Journal of Cerebral Circulation·Anetta UndasHieronim Jakubowski
Dec 4, 2004·Clinical Chemistry·Grazyna Chwatko, Hieronim Jakubowski
Feb 5, 2005·Analytical Biochemistry·Grazyna Chwatko, Hieronim Jakubowski
Feb 16, 2005·Thrombosis and Haemostasis·Anetta UndasAndrzej Szczeklik
Oct 4, 2005·Clinical Chemistry and Laboratory Medicine : CCLM·Hieronim Jakubowski
Apr 1, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Anetta UndasHieronim Jakubowski
May 17, 2006·The Journal of Nutrition·Hieronim Jakubowski
Jun 14, 2006·The British Journal of Nutrition·Naoko EndoTatsuzo Oka
Mar 1, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Grazyna ChwatkoHieronim Jakubowski
Apr 6, 2007·Molecular Genetics and Metabolism·Kevin A StraussS Harvey Mudd
Oct 17, 2007·Clinical Chemistry and Laboratory Medicine : CCLM·Hieronim Jakubowski
May 27, 2008·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Joanna Perła-KajánHieronim Jakubowski
Jun 24, 2008·Analytical Biochemistry·Hieronim Jakubowski

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Citations

Jun 1, 2010·Amino Acids·Rafał GłowackiHieronim Jakubowski
May 31, 2012·Amino Acids·Joanna Perła-Kaján, Hieronim Jakubowski
Feb 11, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hieronim JakubowskiDiana M Shih
Oct 26, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Richard S Beard, Shawn E Bearden
Feb 1, 2011·Clinical Chemistry and Laboratory Medicine : CCLM·Michał ZaąbczykAnetta Undas
Dec 3, 2013·Amino Acids·Marta SikoraHieronim Jakubowski
Nov 14, 2012·Climacteric : the Journal of the International Menopause Society·I LambrinoudakiE Kouskouni
Nov 26, 2015·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Rosanna CoppoGiuseppe Remuzzi
Jun 1, 2010·Journal of Molecular Biology·Paolo PaoliGiampietro Ramponi
Sep 28, 2016·The International Journal of Neuroscience·A Jamroz-WiśniewskaK Rejdak
Apr 20, 2016·Journal of Thrombosis and Haemostasis : JTH·Y C ChungE H Norris
Nov 15, 2018·Physiological Reviews·Hieronim Jakubowski
Nov 3, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Joanna Perła-KajanHieronim Jakubowski
Nov 3, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Joanna Perla-Kaján, Hieronim Jakubowski
Apr 9, 2020·International Journal of Molecular Sciences·Olga UtyroHieronim Jakubowski
May 22, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Joanna Perła-KajánHieronim Jakubowski
Jun 21, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nassila AkchicheJean-Luc Daval
Feb 6, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Khoosheh KhayatiRadek Dobrowolski
Feb 11, 2011·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·S Harvey Mudd
Nov 19, 2011·Wiley Interdisciplinary Reviews. RNA·Hieronim Jakubowski
Feb 20, 2019·International Journal of Molecular Sciences·Ruben EsseRita Castro
Feb 26, 2019·Scientific Reports·Marta SikoraHieronim Jakubowski
Jun 28, 2019·International Journal of Molecular Sciences·Marta SikoraHieronim Jakubowski
Dec 16, 2020·Expert Review of Proteomics·Hieronim Jakubowski
Jul 4, 2019·Biochimie·V Sudhakar ReddyG Bhanuprakash Reddy
Aug 10, 2020·Free Radical Biology & Medicine·Olga UtyroHieronim Jakubowski
Jun 13, 2021·Neuroscience and Biobehavioral Reviews·Gerwyn MorrisBasant K Puri
Oct 6, 2021·Critical Reviews in Biochemistry and Molecular Biology·Jean-Louis GuéantDavid Coelho
Jul 12, 2011·Molecular Genetics and Metabolism·Camila Simioni VanzinCarmen Regla Vargas

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