title: Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects.
abstract: This overview addresses homocysteine and folate metabolism. Its functions and complexity are described, leading to explanations why disturbed homocysteine and folate metabolism is implicated in many different diseases, including congenital birth defects like congenital heart disease, cleft lip and palate, late pregnancy complications, different kinds of neurodegenerative and psychiatric diseases, osteoporosis and cancer. In addition, the inborn errors leading to hyperhomocysteinemia and homocystinuria are described. These extreme human hyperhomocysteinemia models provide knowledge about which part of the homocysteine and folate pathways are linked to which disease. For example, the very high risk for arterial and venous occlusive disease in patients with severe hyperhomocysteinemia irrespective of the location of the defect in remethylation or transsulphuration indicates that homocysteine itself or one of its "direct" derivatives is considered toxic for the cardiovascular system. Finally, common diseases associated with elevated homocysteine are discussed with the focus on cardiovascular disease and neural tube defects.
authors.affiliation: Metabolic Unit, Department of Clinical Chemistry, Institute for Cardiovascular Research (ICaR-VU), VU University Medical Centre, Amsterdam, The Netherlands. h.blom@vumc.nl
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Blom
authors.forename: Yvo
authors.initials: Y
authors.lastname: Smulders
mesh_terms: D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D005260:Female; D005492:Folic Acid / Q000378:metabolism*; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009436:Neural Tube Defects / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D011247:Pregnancy; D012307:Risk Factors
chemical_list: D006710:Homocysteine; D005492:Folic Acid
references.citation: Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):2080-5
references.pmid: 11742888
references.citation: Adv Drug Deliv Rev. 2004 Apr 29;56(8):1085-97
references.pmid: 15094208
references.citation: Birth Defects Res A Clin Mol Teratol. 2009 Apr;85(4):295-302
references.pmid: 19301298
references.citation: Biochem Biophys Res Commun. 1999 Jan 8;254(1):127-37
references.pmid: 9920745
references.citation: Am J Physiol. 1991 Jun;260(6 Pt 1):G865-72
references.pmid: 2058674
references.citation: Lancet. 2007 Jun 2;369(9576):1876-1882
references.pmid: 17544768
references.citation: Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):543-8
references.pmid: 9012820
references.citation: Birth Defects Res C Embryo Today. 2005 Jun;75(2):98-111
references.pmid: 16035040
references.citation: Science. 2001 Aug 10;293(5532):1089-93
references.pmid: 11498579
references.citation: Am J Pathol. 1969 Jul;56(1):111-28
references.pmid: 5792556
references.citation: Am J Clin Nutr. 2000 Aug;72(2):324-32
references.pmid: 10919921
references.citation: Lancet. 1995 Oct 21;346(8982):1070-1
references.pmid: 7564788
references.citation: Birth Defects Res A Clin Mol Teratol. 2006 Jul;76(7):544-52
references.pmid: 16933307
references.citation: Biochem Pharmacol. 1992 Nov 3;44(9):1898-901
references.pmid: 1449544
references.citation: J Med Genet. 2004 Jun;41(6):454-8
references.pmid: 15173232
references.citation: Brain Res Dev Brain Res. 2005 Aug 8;158(1-2):59-65
references.pmid: 15996755
references.citation: Clin Chem Lab Med. 2007;45(12):1694-9
references.pmid: 17963455
references.citation: Teratology. 1990 Oct;42(4):437-51
references.pmid: 2256006
references.citation: Am J Med Genet. 2001 Oct 1;103(2):128-32
references.pmid: 11568918
references.citation: Hum Mol Genet. 1996 Dec;5(12):1851-8
references.pmid: 8968735
references.citation: N Engl J Med. 1992 Dec 24;327(26):1832-5
references.pmid: 1307234
references.citation: Birth Defects Res A Clin Mol Teratol. 2006 Apr;76(4):230-6
references.pmid: 16575882
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5606-11
references.pmid: 11929966
references.citation: Cell. 1999 Oct 29;99(3):247-57
references.pmid: 10555141
references.citation: J Biol Chem. 1958 Mar;231(1):481-92
references.pmid: 13538985
references.citation: Arch Biochem Biophys. 1997 Sep 1;345(1):171-4
references.pmid: 9281325
references.citation: Arch Dis Child. 1976 Dec;51(12):944-50
references.pmid: 1015847
references.citation: Am J Clin Nutr. 2007 Jan;85(1):285S-288S
references.pmid: 17209211
references.citation: J Biol Chem. 1988 Nov 5;263(31):15946-50
references.pmid: 3053686
references.citation: Trends Genet. 1997 Feb;13(2):51-2
references.pmid: 9055605
references.citation: J Biol Chem. 1993 Jun 5;268(16):11910-6
references.pmid: 8505317
references.citation: Cell. 2006 Dec 1;127(5):917-28
references.pmid: 17129779
references.citation: Nat Genet. 1995 May;10(1):111-3
references.pmid: 7647779
references.citation: Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13217-20
references.pmid: 9789068
references.citation: Cochrane Database Syst Rev. 2009 Oct 07;(4):CD006612
references.pmid: 19821378
references.citation: Pharmacol Ther. 1997;73(3):265-80
references.pmid: 9175157
references.citation: Nat Rev Neurosci. 2006 Sep;7(9):724-31
references.pmid: 16924261
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3059-64
references.pmid: 9501215
references.citation: Lancet. 1991 Jul 20;338(8760):131-7
references.pmid: 1677062
references.citation: Mol Genet Metab. 1999 Jan;66(1):1-9
references.pmid: 9973541