Homocysteine: Difference between revisions
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In [[biochemistry]], '''homocysteine''' is a "thiol-containing [[amino acid]] formed by a demethylation of [[methionine]].<ref>{{MeSH}}</ref> | In [[biochemistry]], '''homocysteine''' is a "thiol-containing [[amino acid]] formed by a demethylation of [[methionine]].<ref>{{MeSH}}</ref> | ||
==Role in human disease== | |||
===Homocystinuria=== | |||
{{main|Homocystinuria}} | |||
[[Homocystinuria]] is an "autosomal recessive inborn error of [[methionine]] metabolism usually caused by a deficiency of [[cystathionine beta-synthase]] and associated with elevations of homocysteine in plasma and urine. Clinical features include a tall, slender habitus, [[scoliosis]], [[arachnodactyly]], [[muscle weakness]], [[genu varis]], thin blond hair, malar flush, lens dislocations, an increased incidence of [[mental retardation]], and a tendency to develop fibrosis of arteries, frequently complicated by [[stroke|cerebrovascular accidents]] and [[myocardial infarction]].<ref>{{MeSH}}</ref> Homozygous individuals have homocysteine levels that are five times the normal level.<ref name="pmid17124224">{{cite journal |author=Wald DS, Wald NJ, Morris JK, Law M |title=Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence |journal=BMJ |volume=333 |issue=7578 |pages=1114–7 |year=2006 |month=November |pmid=17124224 |pmc=1661741 |doi=10.1136/bmj.39000.486701.68 |url=http://bmj.com/cgi/pmidlookup?view=long&pmid=17124224 |issn=}}</ref> | |||
===Hyperhomocysteinemia=== | |||
{{main|Hyperhomocysteinemia}} | |||
[[Hyperhomocysteinemia]] is an "inborn error of [[methionine]] metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of [[cystathionine beta-synthase]] and is a risk factor for [[coronary heart disease|coronary vascular disease]]."<ref>{{MeSH|Hyperhomocysteinemia}}</ref><ref name="OMIM - Hyperhomocysteinemia">{{cite web |url=http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603174 |title=Homocysteinemia |author= |authorlink= |coauthors= |date= |format= |work= |publisher=Online Mendelian Inheritance in Man |pages= |language= |archiveurl= |archivedate= |quote= |accessdate=2008-11-16}}</ref> | |||
===Methylenetetrahydrofolate reductase deficiency=== | |||
About 10% of people are homozygous for the single gene mutation (cytosine is replaced by thymidine at base position 677) that reduces the activity of the enzyme [[methylenetetrahydrofolate reductase]] (MTHFR).<ref name="pmid17124224">{{cite journal |author=Wald DS, Wald NJ, Morris JK, Law M |title=Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence |journal=BMJ |volume=333 |issue=7578 |pages=1114–7 |year=2006 |month=November |pmid=17124224 |pmc=1661741 |doi=10.1136/bmj.39000.486701.68 |url=http://bmj.com/cgi/pmidlookup?view=long&pmid=17124224 |issn=}}</ref><ref name="pmid12446535">{{cite journal |author=Wald DS, Law M, Morris JK |title=Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis |journal=BMJ |volume=325 |issue=7374 |pages=1202 |year=2002 |month=November |pmid=12446535 |pmc=135491 |doi= |url=http://bmj.com/cgi/pmidlookup?view=long&pmid=12446535 |issn=}}</ref> These individuals with TT [[genotype]] have a 20% increase in serum homocysteine levels and may have increased [[coronary heart disease]].<ref name="pmid17124224"/><ref name="pmid12446535"/><ref name="OMIM - MTHFR">{{cite web |url=http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607093 |title=5,10-@methylenetetrahydrofolate reductase; MTHFR|author= |authorlink= |coauthors= |date= |format= |work= |publisher=Online Mendelian Inheritance in Man |pages= |language= |archiveurl= |archivedate= |quote= |accessdate=2008-11-16}}</ref> | |||
==Treatment to reduce homocysteine levels== | |||
[[Randomized controlled trial]]s have shown the vitamin supplements can lower the homocysteine level; however, this reduction does not lead to reduced mortality<ref name="pmid17848650">{{cite journal |author=Jamison RL, Hartigan P, Kaufman JS, ''et al'' |title=Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial |journal=JAMA |volume=298 |issue=10 |pages=1163–70 |year=2007 |month=September |pmid=17848650 |doi=10.1001/jama.298.10.1163 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=17848650 |issn=}}</ref><ref name="pmid18714059">{{cite journal |author=Ebbing M, Bleie Ø, Ueland PM, ''et al'' |title=Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial |journal=JAMA |volume=300 |issue=7 |pages=795–804 |year=2008 |month=August |pmid=18714059 |doi=10.1001/jama.300.7.795 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18714059 |issn=}}</ref>, reduced [[coronary heart disease]]<ref name="pmid16531614">{{cite journal |author=Bønaa KH, Njølstad I, Ueland PM, ''et al'' |title=Homocysteine lowering and cardiovascular events after acute myocardial infarction |journal=N. Engl. J. Med. |volume=354 |issue=15 |pages=1578–88 |year=2006 |month=April |pmid=16531614 |doi=10.1056/NEJMoa055227 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=16531614&promo=ONFLNS19 |issn=}}</ref><ref name="pmid18714059"/> or improved cognition<ref name="pmid16807413">{{cite journal |author=McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM |title=A controlled trial of homocysteine lowering and cognitive performance |journal=N. Engl. J. Med. |volume=354 |issue=26 |pages=2764–72 |year=2006 |month=June |pmid=16807413 |doi=10.1056/NEJMoa054025 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=16807413&promo=ONFLNS19 |issn=}}</ref><ref name="pmid18854539">{{cite journal |author=Aisen PS, Schneider LS, Sano M, ''et al'' |title=High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial |journal=JAMA |volume=300 |issue=15 |pages=1774–83 |year=2008 |month=October |pmid=18854539 |doi=10.1001/jama.300.15.1774 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18854539 |issn=}}</ref> | |||
==References== | ==References== | ||
<references/> | <references/> | ||
Revision as of 23:45, 16 November 2008
In biochemistry, homocysteine is a "thiol-containing amino acid formed by a demethylation of methionine.[1]
Role in human disease
Homocystinuria
Homocystinuria is an "autosomal recessive inborn error of methionine metabolism usually caused by a deficiency of cystathionine beta-synthase and associated with elevations of homocysteine in plasma and urine. Clinical features include a tall, slender habitus, scoliosis, arachnodactyly, muscle weakness, genu varis, thin blond hair, malar flush, lens dislocations, an increased incidence of mental retardation, and a tendency to develop fibrosis of arteries, frequently complicated by cerebrovascular accidents and myocardial infarction.[2] Homozygous individuals have homocysteine levels that are five times the normal level.[3]
Hyperhomocysteinemia
Hyperhomocysteinemia is an "inborn error of methionine metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine beta-synthase and is a risk factor for coronary vascular disease."[4][5]
Methylenetetrahydrofolate reductase deficiency
About 10% of people are homozygous for the single gene mutation (cytosine is replaced by thymidine at base position 677) that reduces the activity of the enzyme methylenetetrahydrofolate reductase (MTHFR).[3][6] These individuals with TT genotype have a 20% increase in serum homocysteine levels and may have increased coronary heart disease.[3][6][7]
Treatment to reduce homocysteine levels
Randomized controlled trials have shown the vitamin supplements can lower the homocysteine level; however, this reduction does not lead to reduced mortality[8][9], reduced coronary heart disease[10][9] or improved cognition[11][12]
References
- ↑ Anonymous (2024), Homocysteine (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2024), Homocysteine (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ 3.0 3.1 3.2 Wald DS, Wald NJ, Morris JK, Law M (November 2006). "Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence". BMJ 333 (7578): 1114–7. DOI:10.1136/bmj.39000.486701.68. PMID 17124224. PMC 1661741. Research Blogging.
- ↑ Anonymous (2024), Hyperhomocysteinemia (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Homocysteinemia. Online Mendelian Inheritance in Man. Retrieved on 2008-11-16.
- ↑ 6.0 6.1 Wald DS, Law M, Morris JK (November 2002). "Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis". BMJ 325 (7374): 1202. PMID 12446535. PMC 135491. [e]
- ↑ 5,10-@methylenetetrahydrofolate reductase; MTHFR. Online Mendelian Inheritance in Man. Retrieved on 2008-11-16.
- ↑ Jamison RL, Hartigan P, Kaufman JS, et al (September 2007). "Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial". JAMA 298 (10): 1163–70. DOI:10.1001/jama.298.10.1163. PMID 17848650. Research Blogging.
- ↑ 9.0 9.1 Ebbing M, Bleie Ø, Ueland PM, et al (August 2008). "Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial". JAMA 300 (7): 795–804. DOI:10.1001/jama.300.7.795. PMID 18714059. Research Blogging.
- ↑ Bønaa KH, Njølstad I, Ueland PM, et al (April 2006). "Homocysteine lowering and cardiovascular events after acute myocardial infarction". N. Engl. J. Med. 354 (15): 1578–88. DOI:10.1056/NEJMoa055227. PMID 16531614. Research Blogging.
- ↑ McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM (June 2006). "A controlled trial of homocysteine lowering and cognitive performance". N. Engl. J. Med. 354 (26): 2764–72. DOI:10.1056/NEJMoa054025. PMID 16807413. Research Blogging.
- ↑ Aisen PS, Schneider LS, Sano M, et al (October 2008). "High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial". JAMA 300 (15): 1774–83. DOI:10.1001/jama.300.15.1774. PMID 18854539. Research Blogging.