View source for Homocysteine

{{distinguish|homocystine}}
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 443338221
| ImageFile_Ref = {{chemboximage|correct|??}}
| ImageFile = Homocysteine racemic.png
| ImageSize = 180px
| ImageName = Skeletal formula
| ImageFile1 = L-Homocysteine-3D-balls.png
| ImageSize1 = 120px
| ImageName1 = Ball-and-stick model
| IUPACName = 2-Amino-4-sulfanylbutanoic acid
| OtherNames =
|Section1={{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 757
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C05330
| InChI = 1/C4H9NO2S/c5-3(1-2-8)4(6)7/h3,8H,1-2,5H2,(H,6,7)
| InChIKey = FFFHZYDWPBMWHY-UHFFFAOYAS
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 310604
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C4H9NO2S/c5-3(1-2-8)4(6)7/h3,8H,1-2,5H2,(H,6,7)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = FFFHZYDWPBMWHY-UHFFFAOYSA-N
| CASNo = 454-29-5
| CASNo_Comment = ([[racemate]])<!-- verified via Scifinder-->
| CASNo_Ref = {{cascite|correct|??}}
| CASNo1 = 6027-13-0
| CASNo1_Comment = (<small>L</small>-isomer)<!-- verified via Scifinder-->
| CASNo1_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = S7IJP4A89K 
| UNII_Comment = ([[racemate]])
| UNII1_Ref = {{fdacite|correct|FDA}}
| UNII1 = 0LVT1QZ0BA 
| UNII1_Comment = (<small>L</small>-isomer)
| EC_number = 207-222-9
| PubChem = 778

| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 17230
| SMILES = C(CS)C(C(=O)O)N
}}
|Section2={{Chembox Properties
| Formula = C<sub>4</sub>H<sub>9</sub>NO<sub>2</sub>S
| MolarMass = 135.18 g/mol
| Appearance = White crystalline powder
| Density =
| MeltingPtC = 234–235
| MeltingPt_ref =<ref>{{cite journal|last1=Allen|first1=Milton J.|last2=Steinman|first2=Harry G.|title=The Electrolytic Reduction of Homocystine at a Controlled Reference Potential|journal=Journal of the American Chemical Society|volume=74|issue=15|pages=3932–3933|doi=10.1021/ja01135a502|year=1952|bibcode=1952JAChS..74.3932A }}</ref>
| MeltingPt_notes = (decomposes)
| BoilingPt =
| Solubility = soluble
| LogP = −2.56<ref name=Properties>{{cite journal|last1=Chalcraft|first1=Kenneth R.|last2=Lee|first2=Richard|last3=Mills|first3=Casandra|last4=Britz-McKibbin|first4=Philip|title=Virtual Quantification of Metabolites by Capillary Electrophoresis-Electrospray Ionization-Mass Spectrometry: Predicting Ionization Efficiency Without Chemical Standards|journal=Analytical Chemistry|volume=81|issue=7|pages=2506–2515|doi=10.1021/ac802272u|pmid=19275147|year=2009 |bibcode=2009AnaCh..81.2506C }}</ref>
| pKa = 2.25 <ref name=Properties />
}}
|Section7={{Chembox Hazards
| ExternalSDS = 
| GHSPictograms = {{GHS07}}
| GHSSignalWord = Warning
| HPhrases = {{H-phrases|302}}
| PPhrases = 
 }}
}}

'''Homocysteine''' ({{IPAc-en|ˌ|h|əʊ|m|əʊ|ˈ|s|ɪ|s|t|iː|n}}; symbol '''Hcy''') is a non-proteinogenic [[α-amino acid]]. It is a [[homologous series|homologue]] of the amino acid [[cysteine]], differing by an additional [[methylene bridge]] ({{chem2|\sCH2\s}}). It is biosynthesized from [[methionine]] by the removal of its terminal C<sup>ε</sup> [[methyl group]]. 

Although the production of homocysteine is a normal part of the metabolism of methionine, an excess of homocysteine can be harmful. There are two primary ways for organisms such as humans to metabolize homocysteine: remethylation and transsulfuration. 

[[Remethylation]] adds a [[methyl group]] to the homocysteine molecule, converting homocysteine back into methionine. There are two known remethylation pathways. One pathway requires [[Folate|vitamin B<sub>9</sub>]] (folate) and [[vitamin B12|B<sub>12</sub>]] (cobalamin), which drive the MTR ([[Methionine_synthase|methionine synthase]]) and MTRR ([[MTRR_(gene)|methionine synthase reductase]]) enzymes. The other pathway uses TMG ([[trimethylglycine|trimethylglycine]]) to drive the [[BHMT]] (betaine-homocysteine methyltransferase) enzyme.

[[transsulfuration pathway|Transsulfuration]] converts homocysteine to [[cystathionine]]. This pathway requires [[Vitamin B6|vitamin B<sub>6</sub>]] to drive the CBS ([[Cystathionine-β-synthase|cystathionine beta synthase]]) enzyme.<ref>{{cite web|url=https://dmec.moh.gov.vn/documents/10182/31934092/upload_00034511_1656320270953.pdf?version=1.0&fileId=31960513|title=Homocysteine|access-date=5 April 2023|website=moh.gov.vn}}</ref> Cystathionine is the immediate precursor of the amino acid [[cysteine]], which (along with [[glutamate]] and [[glycine]]), is incorporated into the tripeptide [[glutathione]], a major [[antioxidant]] in the human body.

Homocysteine is therefore an important metabolic substrate. However, excessive levels of homocysteine can result in [[Hyperhomocysteinemia|hyperhomocysteinemia]], which is regarded as an indicator of cardiovascular disease risk. Homocysteine likely contributes to [[atherogenesis]], which can result in [[Ischemia|ischemic injury]]. Therefore, hyperhomocysteinemia is a possible risk factor for [[coronary artery disease]]. Coronary artery disease occurs when an atherosclerotic plaque blocks blood flow to the [[Coronary artery|coronary arteries]], which supply the heart with oxygenated blood.<ref name="pmid29552692">{{cite journal| author=Kim J, Kim H, Roh H, Kwon Y| title=Causes of hyperhomocysteinemia and its pathological significance. | journal=Arch Pharm Res | year= 2018 | volume= 41 | issue= 4 | pages= 372–383 | pmid=29552692 | doi=10.1007/s12272-018-1016-4 | pmc= | s2cid=3986295 }}</ref><ref>{{cite web|last=Boudi|first=Brian F|title=Noncoronary Atherosclerosis|url=http://emedicine.medscape.com/article/1950759-overview#aw2aab6b3|publisher=Medscape|url-status=live|archive-url=https://web.archive.org/web/20130511074608/http://emedicine.medscape.com/article/1950759-overview#aw2aab6b3|archive-date=2013-05-11}}</ref> Hyperhomocysteinemia has also been correlated with the occurrence of blood clots, heart attacks, and strokes, although it is unclear whether hyperhomocysteinemia is an independent risk factor for these conditions.<ref>''[https://www.nutritionletter.tufts.edu/healthy-mind/homocysteine-the-facts Homocysteine: The Facts]'', Tufts Health and Nutrition Letter, July 31, 2020 update</ref> Hyperhomocysteinemia has also been associated with early-term spontaneous abortions<ref name="Cochrane 2015">{{cite journal | pmid = 10725483 | volume=95 | issue=4 | title=Homocysteine and folate levels as risk factors for recurrent early pregnancy loss |vauthors=Nelen WL, Blom HJ, Steegers EA, den Heijer M, Thomas CM, Eskes TK | journal=Obstet Gynecol | pages=519–24 | doi=10.1016/s0029-7844(99)00610-9| year=2000 | s2cid=26125655 }}</ref> and with [[neural tube defects]].<ref>van der Put NJ et al [http://ebm.sagepub.com/content/226/4/243.short Folate, Homocysteine and Neural Tube Defects: An Overview] {{webarchive|url=https://web.archive.org/web/20150916182135/http://ebm.sagepub.com/content/226/4/243.short |date=2015-09-16 }} Exp Biol Med (Maywood) April 2001 vol. 226 no. 4 243-270</ref>

[[Image:Betain-Homocystein.png|236px|left|thumb|[[Zwitterion]]ic forms of (''S'')-homocysteine (left) and (''R'')-homocysteine (right)]]

==Biosynthesis and biochemical roles==

[[Image:Met pathway.svg|thumb|left|Two of homocysteine's main biochemical roles (homocysteine is seen in the left middle of the image). It can be synthesized from methionine and then converted back to methionine via the SAM cycle or used to create cysteine and alpha-ketobutyrate.]]

Homocysteine is biosynthesized naturally via a multi-step process.<ref name="AnRvNutrition1999-Selhub">{{cite journal | author=Selhub, J. | title=Homocysteine metabolism | journal=Annual Review of Nutrition | year=1999 | volume=19 | pages=217–246 | pmid=10448523 | doi=10.1146/annurev.nutr.19.1.217| s2cid=2335090 }}</ref> First, methionine receives an adenosine group from [[Adenosine triphosphate|ATP]], a reaction catalyzed by [[S-adenosyl-methionine synthetase]], to give [[S-adenosyl methionine|''S''-adenosyl methionine]] (SAM). SAM is widely used source of methyl radicals as a cofactor for [[radical SAM enzymes]].  Transfer of the methyl group to an acceptor molecule gives S-adenosyl-homocysteine. [[Hydrolysis]] of this thioether gives <small>L</small>-homocysteine. <small>L</small>-Homocysteine reacts with [[tetrahydrofolate]] (THF) to give [[methionine|<small>L</small>-methionine]].{{huh?|date=April 2025}}<ref>Champe, PC and Harvey, RA. "Biochemistry.  Lippincott's Illustrated Reviews" 4th ed. Lippincott Williams and Wilkins, 2008</ref>

===Biosynthesis of cysteine===
Mammals biosynthesize the amino acid cysteine via homocysteine. [[Cystathionine-beta-synthase|Cystathionine β-synthase]] catalyses the condensation of homocysteine and [[serine]] to give [[cystathionine]]. This reaction uses [[Pyridoxal phosphate]] (vitamin B<sub>6</sub>) as a cofactor. [[Cystathionine gamma-lyase|Cystathionine γ-lyase]] then converts this double amino acid to cysteine, ammonia, and α-ketobutyrate. Bacteria and plants rely on a different pathway to produce cysteine, relying on ''O''-acetylserine.<ref>Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. {{ISBN|1-57259-153-6}}.</ref>

[[Image:MTHFR metabolism.svg|right|thumb|600px|MTHFR metabolism: folate cycle, methionine cycle, trans-sulfuration and [[hyperhomocysteinemia]] - [[5-MTHF]]: 5-methyltetrahydrofolate; 5,10-methyltetrahydrofolate; [[Bcl-2-associated X protein|BAX]]: Bcl-2-associated X protein; [[BHMT]]: betaine-homocysteine S-methyltransferase; [[cystathionine beta synthase|CBS]]: cystathionine beta synthase; [[cystathionine gamma-lyase|CGL]]: cystathionine gamma-lyase; [[dihydrofolate|DHF]]: dihydrofolate (vitamin B9); [[dimethylglycine|DMG]]: dimethylglycine; [[dTMP]]: thymidine monophosphate; [[dUMP]]: deoxyuridine monophosphate; [[Flavin adenine dinucleotide|FAD<sup>+</sup>]] flavine adenine dicucleotide; [[10-formyltetrahydrofolate|FTHF]]: 10-formyltetrahydrofolate; [[methionine synthase|MS]]: methionine synthase; [[MTHFR]]: mehtylenetetrahydrofolate reductase; [[S-adenosyl-L-homocysteine|SAH]]: S-adenosyl-L-homocysteine; [[S-adenosyl-L-methionine|SAME]]: S-adenosyl-L-methionine; [[tetrahydrofolate|THF]]: tetrahydrofolate]]

===Methionine salvage===
Homocysteine can be recycled into [[methionine]]. This process uses N5-methyl tetrahydrofolate as the methyl donor and [[Methylcobalamin]] (vitamin B<sub>12</sub>)-related enzymes. More detail on these enzymes can be found in the article for [[methionine synthase]].

===Other reactions of biochemical significance===
Homocysteine can cyclize to give [[homocysteine thiolactone]], a five-membered [[heterocycle]].  Because of this "self-looping" reaction, homocysteine-containing [[peptide]]s tend to cleave themselves by reactions generating [[oxidative stress]].<ref>{{cite journal | pmid=20080717 | doi=10.1073/pnas.0909737107 | volume=107 | issue=2 | title=Homocystamides promote free-radical and oxidative damage to proteins | pmc=2818928 | date=January 2010 | vauthors=Sibrian-Vazquez M, Escobedo JO, Lim S, Samoei GK, Strongin RM | journal=Proc. Natl. Acad. Sci. U.S.A. | pages=551–4 | bibcode=2010PNAS..107..551S | doi-access=free }}</ref>

Homocysteine also acts as an [[allosteric modulator|allosteric antagonist]] at Dopamine D<sub>2</sub> receptors.<ref>{{cite journal|last=Agnati|first=LF|author2=Ferré, S|author3=Genedani, S|author4=Leo, G|author5=Guidolin, D|author6=Filaferro, M|author7=Carriba, P|author8=Casadó, V|author9=Lluis, C|author10=Franco, R|author11=Woods, AS|author12=Fuxe, K|title=Allosteric modulation of dopamine D2 receptors by homocysteine|journal=Journal of Proteome Research|date=Nov 2006|volume=5|issue=11|pages=3077–83|pmid=17081059|doi=10.1021/pr0601382|hdl=11380/307098 |url=http://www.cigs.unimo.it/cigsdownloads/labs/cnf_sp2/pubblicazioni/19-agnati%20allosteric%20modulation.pdf|url-status=live|archive-url=https://web.archive.org/web/20170809142808/http://www.cigs.unimo.it/CigsDownloads/labs/cnf_sp2/pubblicazioni/19-Agnati%20allosteric%20modulation.pdf|archive-date=2017-08-09|citeseerx=10.1.1.625.26}}</ref>

It has been proposed that both homocysteine and its thiolactone may have played a significant role in the [[Abiogenesis|appearance of life]] on the early Earth.<ref>{{Cite journal|last1=Vallee|first1=Yannick|last2=Shalayel|first2=Ibrahim|last3=Ly|first3=Kieu-Dung|last4=Rao|first4=K. V. Raghavendra|last5=Paëpe|first5=Gael De|last6=Märker|first6=Katharina|last7=Milet|first7=Anne|date=2017-11-08|title=At the very beginning of life on Earth: the thiol-rich peptide (TRP) world hypothesis|url=http://www.ijdb.ehu.es/web/paper/170028yv/at-the-very-beginning-of-life-on-earth-the-thiol-rich-peptide-trp-world-hypothesis|journal=International Journal of Developmental Biology|volume=61|issue=8–9|pages=471–478|doi=10.1387/ijdb.170028yv|pmid=29139533|issn=0214-6282|doi-access=free|url-access=subscription}}</ref>

==Homocysteine levels==

[[File:Plasma tHcy.svg|thumb|right|Total plasma homocysteine]]

Homocysteine levels typically are higher in men than women, and increase with age.<ref>{{cite journal|last=Nygård|first=O|author2=Vollset, SE |author3=Refsum, H |author4=Stensvold, I |author5=Tverdal, A |author6=Nordrehaug, JE |author7=Ueland, M |author8= Kvåle, G |title=Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study|journal=JAMA: The Journal of the American Medical Association|date=Nov 15, 1995|volume=274|issue=19|pages=1526–33|pmid=7474221|doi=10.1001/jama.274.19.1526}}</ref><ref>{{cite journal|last=Refsum|first=H|author2=Nurk, E |author3=Smith, AD |author4=Ueland, PM |author5=Gjesdal, CG |author6=Bjelland, I |author7=Tverdal, A |author8=Tell, GS |author9=Nygård, O |author10= Vollset, SE |title=The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease|journal=The Journal of Nutrition|date=June 2006|volume=136|issue=6 Suppl|pages=1731S–1740S|pmid=16702348|doi=10.1093/jn/136.6.1731S|doi-access=free}}</ref>

Common levels in Western populations are 10 to 12&nbsp;μmol/L, and levels of 20&nbsp;μmol/L are found in populations with low B-vitamin intakes or in the elderly (e.g., Rotterdam, Framingham).<ref>{{Cite journal|last1=Bots|first1=Michiel L.|last2=Launer|first2=Lenore J.|last3=Lindemans|first3=Jan|last4=Hoes|first4=Arno W.|last5=Hofman|first5=Albert|last6=Witteman|first6=Jacqueline C. M.|last7=Koudstaal|first7=Peter J.|last8=Grobbee|first8=Diederick E.|date=1999-01-11|title=Homocysteine and Short-term Risk of Myocardial Infarction and Stroke in the Elderly|journal=Archives of Internal Medicine|volume=159|issue=1|pages=38–44|doi=10.1001/archinte.159.1.38|pmid=9892328|issn=0003-9926|doi-access=free|hdl=1765/55858|hdl-access=free}}</ref><ref>{{Cite journal|last1=Selhub|first1=J.|last2=Jacques|first2=P. F.|last3=Bostom|first3=A. G.|last4=Wilson|first4=P. W.|last5=Rosenberg|first5=I. H.|date=2000|title=Relationship between plasma homocysteine and vitamin status in the Framingham study population. Impact of folic acid fortification|journal=Public Health Reviews|volume=28|issue=1–4|pages=117–145|issn=0301-0422|pmid=11411265}}</ref>

It is decreased with methyl folate trapping, where it is accompanied by decreased methylmalonic acid, increased folate, and a decrease in [[formiminoglutamic acid]].<ref>{{cite journal |last1=Scott |first1=JohnM. |last2=Weir |first2=DonaldG. |title=THE METHYL FOLATE TRAP: A physiological response in man to prevent methyl group deficiency in kwashiorkor (methionine deficiency) and an explanation for folic-acid-induced exacerbation of subacute combined degeneration in pernicious anaemia |journal=The Lancet |date=15 August 1981 |volume=318 |issue=8242 |pages=337–340 |doi=10.1016/S0140-6736(81)90650-4 |pmid=6115113 |s2cid=29977127 |issn=0140-6736}}</ref> This is the opposite of MTHFR C677T mutations, which result in an increase in homocysteine.{{citation needed|date=June 2019}}

{{anchor|ranges}}
{| class="wikitable"
 |+[[Reference ranges for blood tests|Blood reference ranges]] for homocysteine:
 |-
 |'''Sex'''||'''Age'''||'''Lower limit'''||'''Upper limit'''||'''Unit'''||'''Elevated'''||'''[[Optimal health range|Therapeutic target]]'''
 |- 
| rowspan =4| Female ||rowspan=2| 12–19 years || 3.3<ref name=doctorsdoctor>{{cite web|url=http://www.thedoctorsdoctor.com/labtests/homocysteine.htm|title=Homocysteine|website=www.thedoctorsdoctor.com|archive-url=https://web.archive.org/web/20081205050029/http://www.thedoctorsdoctor.com/labtests/homocysteine.htm|archive-date=2008-12-05|access-date=2008-11-22}}</ref> || 7.2<ref name=doctorsdoctor/> || μmol/L ||rowspan=4| > 10.4 μmol/L <br /> or <br /> > 140 μg/dl  ||rowspan=8| < 6.3 μmol/L<ref name=adeeva>[http://www.adeeva.com/resources/bloodtestscomplete.html Adëeva Nutritionals Canada > Optimal blood test values] {{webarchive|url=https://web.archive.org/web/20090529032656/http://adeeva.com/resources/bloodtestscomplete.html |date=2009-05-29 }} Retrieved on July 9, 2009</ref> <br />or<br /> < 85 μg/dL<ref name=adeeva/> 
 |-
 | 45<ref name=homocysteine-molar>Derived from molar values using molar massof 135 g/mol</ref> || 100<ref name=homocysteine-molar/> || μg/dL
 |- 
| rowspan =2| >60 years || 4.9<ref name=doctorsdoctor/> || 11.6<ref name=doctorsdoctor/> ||μmol/L
 |-
 | 66<ref name=homocysteine-molar/> || 160<ref name=homocysteine-molar/> || μg/dL
 |- 
| rowspan =4| Male ||rowspan=2| 12–19 years || 4.3<ref name=doctorsdoctor/> || 9.9<ref name=doctorsdoctor/> || μmol/L ||rowspan=4| > 11.4 μmol/L <br /> or <br /> > 150 μg/dL
 |-
 | 60<ref name=homocysteine-molar/> || 130<ref name=homocysteine-molar/> || μg/dL
 |- 
| rowspan =2| >60 years || 5.9<ref name=doctorsdoctor/> || 15.3<ref name=doctorsdoctor/> ||μmol/L
 |-
 | 80<ref name=homocysteine-molar/> || 210<ref name=homocysteine-molar/> || μg/dL
 |-
 |}
The ranges above are provided as examples only; test results always should be interpreted using the range provided by the laboratory that produced the result.

==Elevated homocysteine==
{{Main|Hyperhomocysteinemia}}
Abnormally high levels of homocysteine in the serum, above 15 μmol/L, are a medical condition called [[hyperhomocysteinemia]].<ref>{{cite web|url=http://www.merckmanuals.com/professional/hematology-and-oncology/thrombotic-disorders/hyperhomocysteinemia#v12779073|title=Hyperhomocysteinemia - Hematology and Oncology - Merck Manuals Professional Edition|website=merckmanuals.com|url-status=live|archive-url=https://web.archive.org/web/20170609083346/http://www.merckmanuals.com/professional/hematology-and-oncology/thrombotic-disorders/hyperhomocysteinemia#v12779073|archive-date=2017-06-09}}</ref> This has been claimed to be a significant risk factor for the development of a wide range of diseases, in total more than 100<ref>{{Cite journal |last1=Smith |first1=A. D. |last2=Refsum |first2=H. |date=October 2021 |title=Homocysteine – from disease biomarker to disease prevention |url=https://onlinelibrary.wiley.com/doi/10.1111/joim.13279 |journal=Journal of Internal Medicine |volume=290 |issue=4 |pages=826–854 |doi=10.1111/joim.13279 |pmid=33660358 |issn=0954-6820|url-access=subscription }}</ref> including [[thrombosis]],<ref>{{cite journal|last=Cattaneo|first=M|title=Hyperhomocysteinemia, atherosclerosis and thrombosis|journal=Thrombosis and Haemostasis|date=February 1999|volume=81|issue=2|pages=165–76|pmid=10063987|doi=10.1055/s-0037-1614438|s2cid=13228673}}</ref> neuropsychiatric illness,<ref>{{cite journal|last=Morris|first=MS|title=Homocysteine and Alzheimer's disease|journal=Lancet Neurology|date=July 2003|volume=2|issue=7|pages=425–8|pmid=12849121|doi=10.1016/s1474-4422(03)00438-1|s2cid=20443022}}</ref><ref>{{cite journal |last1=Smach |first1=MA |last2=Jacob |first2=N |last3=Golmard |first3=JL |last4=Charfeddine |first4=B |last5=Lammouchi |first5=T |last6=Ben Othman |first6=L |last7=Dridi |first7=H |last8=Bennamou |first8=S |last9=Limem |first9=K |title=Folate and homocysteine in the cerebrospinal fluid of patients with Alzheimer's disease or dementia: a case control study |journal=European Neurology |year=2011 |volume=65 |issue=5 |pages=270–8 |pmid=21474939 |doi=10.1159/000326301|s2cid=7689901 }}</ref><ref>{{cite journal |last1=Smith |first1=AD |last2=Smith |first2=SM |last3=de Jager |first3=CA |last4=Whitbread |first4=P |last5=Johnston |first5=C |last6=Agacinski |first6=G |last7=Oulhaj |first7=A |last8=Bradley |first8=KM |last9=Jacoby |first9=R |last10=Refsum |first10=H |title=Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial |journal=PLOS ONE |date=Sep 8, 2010 |volume=5 |issue=9 |article-number=e12244 |pmid=20838622 |doi=10.1371/journal.pone.0012244 |pmc=2935890|bibcode=2010PLoSO...512244S |doi-access=free }}</ref><ref>{{cite journal|last=Dietrich-Muszalska|first=A|author2=Malinowska, J |author3=Olas, B |author4=Głowacki, R |author5=Bald, E |author6=Wachowicz, B |author7= Rabe-Jabłońska, J |title=The oxidative stress may be induced by the elevated homocysteine in schizophrenic patients|journal=Neurochemical Research|date=May 2012|volume=37|issue=5|pages=1057–62|pmid=22270909|doi=10.1007/s11064-012-0707-3|pmc=3321271}}</ref> in particular dementia<ref>{{Cite journal |last1=Smith |first1=A. David |last2=Refsum |first2=Helga |last3=Bottiglieri |first3=Teodoro |last4=Fenech |first4=Michael |last5=Hooshmand |first5=Babak |last6=McCaddon |first6=Andrew |last7=Miller |first7=Joshua W. |last8=Rosenberg |first8=Irwin H. |last9=Obeid |first9=Rima |date=2018 |title=Homocysteine and Dementia: An International Consensus Statement |url=https://www.researchwithrutgers.com/en/publications/homocysteine-and-dementia-an-international-consensus-statement |journal=Journal of Alzheimer's Disease |volume=62 |issue=2 |pages=561–570 |doi=10.3233/JAD-171042 |issn=1387-2877 |pmid=29480200|pmc=5836397 |hdl=10852/67691 |hdl-access=free }}</ref> and fractures.<ref>{{cite journal|last=McLean|first=RR|author2=Jacques, PF |author3=Selhub, J |author4=Tucker, KL |author5=Samelson, EJ |author6=Broe, KE |author7=Hannan, MT |author8=Cupples, LA |author9= Kiel, DP |title=Homocysteine as a predictive factor for hip fracture in older persons|journal=The New England Journal of Medicine|date=May 13, 2004|volume=350|issue=20|pages=2042–9|pmid=15141042|doi=10.1056/NEJMoa032739|s2cid=22853996|doi-access=free}}</ref><ref>{{cite journal |last1=van Meurs |first1=JB |last2=Dhonukshe-Rutten |first2=RA |last3=Pluijm |first3=SM |last4=van der Klift |first4=M |last5=de Jonge |first5=R |last6=Lindemans |first6=J |last7=de Groot |first7=LC |last8=Hofman |first8=A |last9=Witteman |first9=JC |last10=van Leeuwen |first10=JP |last11=Breteler |first11=MM |last12=Lips |first12=P |last13=Pols |first13=HA |last14=Uitterlinden |first14=AG |title=Homocysteine levels and the risk of osteoporotic fracture |journal=The New England Journal of Medicine |date=May 13, 2004 |volume=350 |issue=20 |pages=2033–41 |pmid=15141041 |doi=10.1056/NEJMoa032546|url=http://repub.eur.nl/pub/8452 |hdl=1765/8452 |hdl-access=free }}</ref> It also is found to be associated with microalbuminuria ([[Microalbuminuria|moderately increased albuminuria]]), which is a strong indicator of the risk of future cardiovascular disease and renal dysfunction.<ref>{{cite journal |last1=Jager |first1=A |last2=Kostense |first2=PJ |last3=Nijpels |first3=G |last4=Dekker |first4=JM |last5=Heine |first5=RJ |last6=Bouter |first6=LM |last7=Donker |first7=AJ |last8=Stehouwer |first8=CD |title=Serum homocysteine levels are associated with the development of (micro)albuminuria: the Hoorn study |journal=Arteriosclerosis, Thrombosis, and Vascular Biology |date=Jan 2001 |volume=21 |issue=1 |pages=74–81 |doi=10.1161/01.ATV.21.1.74 |pmid=11145936|doi-access=free }}</ref> Vitamin B<sub>12</sub> deficiency, even when coupled with high serum folate levels, has been found to increase overall homocysteine concentrations as well.<ref>{{Cite journal|last1=Selhub|first1=J.|last2=Morris|first2=M. S.|last3=Jacques|first3=P. F.|date=2007-12-04|title=In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations|journal=Proceedings of the National Academy of Sciences|volume=104|issue=50|pages=19995–20000|doi=10.1073/pnas.0709487104|pmid=18056804|pmc=2148411|bibcode=2007PNAS..10419995S|issn=0027-8424|doi-access=free}}</ref>

Typically, hyperhomocysteinemia is managed with vitamin B<sub>6</sub>, vitamin B<sub>9</sub>, and vitamin B<sub>12</sub> supplementation.<ref name="ExpertOpPharm2001-Coen">{{cite journal |doi=10.1517/14656566.2.9.1449 |pmid=11585023 |title=Homocysteine-lowering treatment: An overview |journal=Expert Opinion on Pharmacotherapy |volume=2 |issue=9 |pages=1449–60 |year=2005 |last1=Stehouwer |first1=Coen DA |last2=Guldener |first2=Coen van |s2cid=45945199 }}</ref> However, supplementation with these vitamins does not appear to improve cardiovascular disease outcomes.<ref name="Art2015">{{cite journal|last1=Martí-Carvajal|first1=Arturo J.|last2=Solà|first2=Ivan|last3=Lathyris|first3=Dimitrios|date=15 January 2015|editor1-last=Martí-Carvajal|editor1-first=Arturo J|title=Homocysteine-lowering interventions for preventing cardiovascular events|journal=The Cochrane Database of Systematic Reviews|volume=1|article-number=CD006612|doi=10.1002/14651858.CD006612.pub4|issn=1469-493X|pmc=4164174|pmid=25590290}}</ref>

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== References ==
{{Reflist}}

==External links==
{{Wikiversity|Homocysteine}}
* [http://gmd.mpimp-golm.mpg.de/Spectrums/2115c92f-87df-468a-a708-c16705b68729.aspx Homocysteine MS Spectrum]
* Homocysteine at [https://www.testing.com/tests/homocysteine/ Lab Tests Online]
*[http://www.abc.net.au/rn/healthreport/stories/2010/2905728.htm Prof. David Spence on homocysteine levels, kidney damage, and cardiovascular disease], ''The Health Report'', Radio National, 24 May 2010

{{Amino acid metabolism intermediates}}
{{Authority control}}

[[Category:Alpha-Amino acids]]
[[Category:Sulfur amino acids]]
[[Category:Thiols]]
[[Category:Non-proteinogenic amino acids]]
[[Category:Excitatory amino acids]]