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Wikipedia

Homocysteine

October 14, 2023

Not to be confused with homocystine.

Homocysteine /ˌhoʊmoʊˈsɪstiːn/ or Hcy: is a non-proteinogenic α-amino acid. It is a homologue of the amino acid cysteine, differing by an additional methylene bridge (-CH2-). It is biosynthesized from methionine by the removal of its terminal Cε methyl group. In the body, homocysteine can be recycled into methionine or converted into cysteine with the aid of vitamin B6, B9, and B12.[3]

Homocysteine
Names
IUPAC name
2-Amino-4-sulfanylbutanoic acid
Identifiers
  • 454-29-5 (racemate) Y
  • 6027-13-0 (L-isomer) Y
3D model (JSmol)
  • Interactive image
ChEBI
  • CHEBI:17230 Y
ChEMBL
  • ChEMBL310604 Y
ChemSpider
  • 757 Y
ECHA InfoCard 100.006.567
EC Number
  • 207-222-9
KEGG
  • C05330 Y
  • 778
UNII
  • S7IJP4A89K (racemate) Y
  • 0LVT1QZ0BA (L-isomer) Y
  • InChI=1S/C4H9NO2S/c5-3(1-2-8)4(6)7/h3,8H,1-2,5H2,(H,6,7) Y
    Key: FFFHZYDWPBMWHY-UHFFFAOYSA-N Y
  • InChI=1/C4H9NO2S/c5-3(1-2-8)4(6)7/h3,8H,1-2,5H2,(H,6,7)
    Key: FFFHZYDWPBMWHY-UHFFFAOYAS
  • C(CS)C(C(=O)O)N
Properties
C4H9NO2S
Molar mass 135.18 g/mol
Appearance White crystalline powder
Melting point 234–235 °C (453–455 °F; 507–508 K)[2] (decomposes)
soluble
log P -2.56 [1]
Acidity (pKa) 2.25 [1]
Hazards
GHS labelling:
Warning
H302
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)

High levels of homocysteine in the blood (hyperhomocysteinemia) is regarded as a marker of cardiovascular disease, likely working through atherogenesis, which can result in 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 arteries, which supply the heart with oxygenated blood.[4] [5]

Hyperhomocysteinemia has 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.[6] Hyperhomocysteinemia also has been associated with early-term spontaneous abortions[7] and with neural tube defects.[8]

Structure Edit

 
Zwitterionic form of (S)-homocysteine (left) and (R)-homocysteine (right)

Homocysteine exists at neutral pH values as a zwitterion.

Biosynthesis and biochemical roles Edit

 
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.[9] First, methionine receives an adenosine group from ATP, a reaction catalyzed by S-adenosyl-methionine synthetase, to give S-adenosyl methionine (SAM-e). SAM-e then transfers the methyl group to an acceptor molecule, (e.g., norepinephrine as an acceptor during epinephrine synthesis, DNA methyltransferase as an intermediate acceptor in the process of DNA methylation). The adenosine is then hydrolyzed to yield L-homocysteine. L-Homocysteine has two primary fates: conversion via tetrahydrofolate (THF) back into L-methionine or conversion to L-cysteine.[10]

Biosynthesis of cysteine Edit

Mammals biosynthesize the amino acid cysteine via homocysteine. Cystathionine β-synthase catalyses the condensation of homocysteine and serine to give cystathionine. This reaction uses pyridoxine (vitamin B6) as a cofactor. 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.[11]

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

Methionine salvage Edit

Homocysteine can be recycled into methionine. This process uses N5-methyl tetrahydrofolate as the methyl donor and cobalamin (vitamin B12)-related enzymes. More detail on these enzymes can be found in the article for methionine synthase.

Other reactions of biochemical significance Edit

Homocysteine can cyclize to give homocysteine thiolactone, a five-membered heterocycle. Because of this "self-looping" reaction, homocysteine-containing peptides tend to cleave themselves by reactions generating oxidative stress.[12]

Homocysteine also acts as an allosteric antagonist at Dopamine D2 receptors.[13]

It has been proposed that both homocysteine and its thiolactone may have played a significant role in the appearance of life on the early Earth.[14]

Homocysteine levels Edit

 
Total plasma homocysteine

Homocysteine levels typically are higher in men than women, and increase with age.[15][16]

Common levels in Western populations are 10 to 12 μmol/L, and levels of 20 μmol/L are found in populations with low B-vitamin intakes or in the elderly (e.g., Rotterdam, Framingham).[17][18]

It is decreased with methyl folate trapping, where it is accompanied by decreased methylmalonic acid, increased folate, and a decrease in formiminoglutamic acid.[19] This is the opposite of MTHFR C677T mutations, which result in an increase in homocysteine.[citation needed]

Blood reference ranges for homocysteine:
Sex Age Lower limit Upper limit Unit Elevated Therapeutic target
Female 12–19 years 3.3[20] 7.2[20] μmol/L > 10.4 μmol/L
or
> 140 μg/dl		 < 6.3 μmol/L[21]
or
< 85 μg/dL[21]
45[22] 100[22] μg/dL
>60 years 4.9[20] 11.6[20] μmol/L
66[22] 160[22] μg/dL
Male 12–19 years 4.3[20] 9.9[20] μmol/L > 11.4 μmol/L
or
> 150 μg/dL
60[22] 130[22] μg/dL
>60 years 5.9[20] 15.3[20] μmol/L
80[22] 210[22] 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 Edit

Main article: Hyperhomocysteinemia

Abnormally high levels of homocysteine in the serum, above 15 μmol/L, are a medical condition called hyperhomocysteinemia.[23] This has been claimed to be a significant risk factor for the development of a wide range of diseases, including thrombosis,[24] neuropsychiatric illness,[25][26][27][28] and fractures.[29][30] It also is found to be associated with microalbuminuria, which is a strong indicator of the risk of future cardiovascular disease and renal dysfunction.[31] Vitamin B12 deficiency, when coupled with high serum folate levels, has been found to increase overall homocysteine concentrations as well.[32]

Typically, hyperhomocysteinemia is managed with vitamin B6, vitamin B9, and vitamin B12 supplementation.[33] However, supplementation with these vitamins does not appear to improve cardiovascular disease outcomes.[34]

References Edit

  1. ^ a b Chalcraft, Kenneth R.; Lee, Richard; Mills, Casandra; Britz-McKibbin, Philip (2009). "Virtual Quantification of Metabolites by Capillary Electrophoresis-Electrospray Ionization-Mass Spectrometry: Predicting Ionization Efficiency Without Chemical Standards". Analytical Chemistry. 81 (7): 2506–2515. doi:10.1021/ac802272u. PMID 19275147.
  2. ^ Allen, Milton J.; Steinman, Harry G. (1952). "The Electrolytic Reduction of Homocystine at a Controlled Reference Potential". Journal of the American Chemical Society. 74 (15): 3932–3933. doi:10.1021/ja01135a502.
  3. ^ "Homocysteine" (PDF). moh.gov.vn. Retrieved 5 April 2023.
  4. ^ Kim J, Kim H, Roh H, Kwon Y (2018). "Causes of hyperhomocysteinemia and its pathological significance". Arch Pharm Res. 41 (4): 372–383. doi:10.1007/s12272-018-1016-4. PMID 29552692. S2CID 3986295.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Boudi, Brian F. "Noncoronary Atherosclerosis". Medscape. from the original on 2013-05-11.
  6. ^ Homocysteine: The Facts, Tufts Health and Nutrition Letter, July 31, 2020 update
  7. ^ Nelen WL, Blom HJ, Steegers EA, den Heijer M, Thomas CM, Eskes TK (2000). "Homocysteine and folate levels as risk factors for recurrent early pregnancy loss". Obstet Gynecol. 95 (4): 519–24. doi:10.1016/s0029-7844(99)00610-9. PMID 10725483. S2CID 26125655.
  8. ^ van der Put NJ et al Folate, Homocysteine and Neural Tube Defects: An Overview 2015-09-16 at the Wayback Machine Exp Biol Med (Maywood) April 2001 vol. 226 no. 4 243-270
  9. ^ Selhub, J. (1999). "Homocysteine metabolism". Annual Review of Nutrition. 19: 217–246. doi:10.1146/annurev.nutr.19.1.217. PMID 10448523. S2CID 2335090.
  10. ^ Champe, PC and Harvey, RA. "Biochemistry. Lippincott's Illustrated Reviews" 4th ed. Lippincott Williams and Wilkins, 2008
  11. ^ Nelson, D. L.; Cox, M. M. "Lehninger, Principles of Biochemistry" 3rd Ed. Worth Publishing: New York, 2000. ISBN 1-57259-153-6.
  12. ^ Sibrian-Vazquez M, Escobedo JO, Lim S, Samoei GK, Strongin RM (January 2010). "Homocystamides promote free-radical and oxidative damage to proteins". Proc. Natl. Acad. Sci. U.S.A. 107 (2): 551–4. Bibcode:2010PNAS..107..551S. doi:10.1073/pnas.0909737107. PMC 2818928. PMID 20080717.
  13. ^ Agnati, LF; Ferré, S; Genedani, S; Leo, G; Guidolin, D; Filaferro, M; Carriba, P; Casadó, V; Lluis, C; Franco, R; Woods, AS; Fuxe, K (Nov 2006). "Allosteric modulation of dopamine D2 receptors by homocysteine" (PDF). Journal of Proteome Research. 5 (11): 3077–83. CiteSeerX 10.1.1.625.26. doi:10.1021/pr0601382. PMID 17081059. (PDF) from the original on 2017-08-09.
  14. ^ Vallee, Yannick; Shalayel, Ibrahim; Ly, Kieu-Dung; Rao, K. V. Raghavendra; Paëpe, Gael De; Märker, Katharina; Milet, Anne (2017-11-08). "At the very beginning of life on Earth: the thiol-rich peptide (TRP) world hypothesis". International Journal of Developmental Biology. 61 (8–9): 471–478. doi:10.1387/ijdb.170028yv. ISSN 0214-6282. PMID 29139533.
  15. ^ Nygård, O; Vollset, SE; Refsum, H; Stensvold, I; Tverdal, A; Nordrehaug, JE; Ueland, M; Kvåle, G (Nov 15, 1995). "Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study". JAMA: The Journal of the American Medical Association. 274 (19): 1526–33. doi:10.1001/jama.274.19.1526. PMID 7474221.
  16. ^ Refsum, H; Nurk, E; Smith, AD; Ueland, PM; Gjesdal, CG; Bjelland, I; Tverdal, A; Tell, GS; Nygård, O; Vollset, SE (June 2006). "The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease". The Journal of Nutrition. 136 (6 Suppl): 1731S–1740S. doi:10.1093/jn/136.6.1731S. PMID 16702348.
  17. ^ Bots, Michiel L.; Launer, Lenore J.; Lindemans, Jan; Hoes, Arno W.; Hofman, Albert; Witteman, Jacqueline C. M.; Koudstaal, Peter J.; Grobbee, Diederick E. (1999-01-11). "Homocysteine and Short-term Risk of Myocardial Infarction and Stroke in the Elderly". Archives of Internal Medicine. 159 (1): 38–44. doi:10.1001/archinte.159.1.38. ISSN 0003-9926. PMID 9892328.
  18. ^ Selhub, J.; Jacques, P. F.; Bostom, A. G.; Wilson, P. W.; Rosenberg, I. H. (2000). "Relationship between plasma homocysteine and vitamin status in the Framingham study population. Impact of folic acid fortification". Public Health Reviews. 28 (1–4): 117–145. ISSN 0301-0422. PMID 11411265.
  19. ^ Scott, JohnM.; Weir, DonaldG. (15 August 1981). "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". The Lancet. 318 (8242): 337–340. doi:10.1016/S0140-6736(81)90650-4. ISSN 0140-6736. PMID 6115113. S2CID 29977127.
  20. ^ a b c d e f g h . www.thedoctorsdoctor.com. Archived from the original on 2008-12-05. Retrieved 2008-11-22.
  21. ^ a b Adëeva Nutritionals Canada > Optimal blood test values 2009-05-29 at the Wayback Machine Retrieved on July 9, 2009
  22. ^ a b c d e f g h Derived from molar values using molar massof 135 g/mol
  23. ^ "Hyperhomocysteinemia - Hematology and Oncology - Merck Manuals Professional Edition". merckmanuals.com. from the original on 2017-06-09.
  24. ^ Cattaneo, M (February 1999). "Hyperhomocysteinemia, atherosclerosis and thrombosis". Thrombosis and Haemostasis. 81 (2): 165–76. doi:10.1055/s-0037-1614438. PMID 10063987. S2CID 13228673.
  25. ^ Morris, MS (July 2003). "Homocysteine and Alzheimer's disease". Lancet Neurology. 2 (7): 425–8. doi:10.1016/s1474-4422(03)00438-1. PMID 12849121. S2CID 20443022.
  26. ^ Smach, MA; Jacob, N; Golmard, JL; Charfeddine, B; Lammouchi, T; Ben Othman, L; Dridi, H; Bennamou, S; Limem, K (2011). "Folate and homocysteine in the cerebrospinal fluid of patients with Alzheimer's disease or dementia: a case control study". European Neurology. 65 (5): 270–8. doi:10.1159/000326301. PMID 21474939. S2CID 7689901.
  27. ^ Smith, AD; Smith, SM; de Jager, CA; Whitbread, P; Johnston, C; Agacinski, G; Oulhaj, A; Bradley, KM; Jacoby, R; Refsum, H (Sep 8, 2010). "Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial". PLOS ONE. 5 (9): e12244. Bibcode:2010PLoSO...512244S. doi:10.1371/journal.pone.0012244. PMC 2935890. PMID 20838622.
  28. ^ Dietrich-Muszalska, A; Malinowska, J; Olas, B; Głowacki, R; Bald, E; Wachowicz, B; Rabe-Jabłońska, J (May 2012). "The oxidative stress may be induced by the elevated homocysteine in schizophrenic patients". Neurochemical Research. 37 (5): 1057–62. doi:10.1007/s11064-012-0707-3. PMC 3321271. PMID 22270909.
  29. ^ McLean, RR; Jacques, PF; Selhub, J; Tucker, KL; Samelson, EJ; Broe, KE; Hannan, MT; Cupples, LA; Kiel, DP (May 13, 2004). "Homocysteine as a predictive factor for hip fracture in older persons". The New England Journal of Medicine. 350 (20): 2042–9. doi:10.1056/NEJMoa032739. PMID 15141042. S2CID 22853996.
  30. ^ van Meurs, JB; Dhonukshe-Rutten, RA; Pluijm, SM; van der Klift, M; de Jonge, R; Lindemans, J; de Groot, LC; Hofman, A; Witteman, JC; van Leeuwen, JP; Breteler, MM; Lips, P; Pols, HA; Uitterlinden, AG (May 13, 2004). "Homocysteine levels and the risk of osteoporotic fracture". The New England Journal of Medicine. 350 (20): 2033–41. doi:10.1056/NEJMoa032546. hdl:1765/8452. PMID 15141041.
  31. ^ Jager, A; Kostense, PJ; Nijpels, G; Dekker, JM; Heine, RJ; Bouter, LM; Donker, AJ; Stehouwer, CD (Jan 2001). "Serum homocysteine levels are associated with the development of (micro)albuminuria: the Hoorn study". Arteriosclerosis, Thrombosis, and Vascular Biology. 21 (1): 74–81. doi:10.1161/01.ATV.21.1.74. PMID 11145936.
  32. ^ Selhub, J.; Morris, M. S.; Jacques, P. F. (2007-12-04). "In vitamin B12 deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations". Proceedings of the National Academy of Sciences. 104 (50): 19995–20000. Bibcode:2007PNAS..10419995S. doi:10.1073/pnas.0709487104. ISSN 0027-8424. PMC 2148411. PMID 18056804.
  33. ^ Stehouwer, Coen DA; Guldener, Coen van (2005). "Homocysteine-lowering treatment: An overview". Expert Opinion on Pharmacotherapy. 2 (9): 1449–60. doi:10.1517/14656566.2.9.1449. PMID 11585023. S2CID 45945199.
  34. ^ Martí-Carvajal, Arturo J.; Solà, Ivan; Lathyris, Dimitrios (15 January 2015). Martí-Carvajal, Arturo J (ed.). "Homocysteine-lowering interventions for preventing cardiovascular events". The Cochrane Database of Systematic Reviews. 1: CD006612. doi:10.1002/14651858.CD006612.pub4. ISSN 1469-493X. PMC 4164174. PMID 25590290.

External links Edit

 
Wikiversity has learning resources about Homocysteine
  • Homocysteine MS Spectrum
  • Homocysteine at Lab Tests Online
  • Homocysteine: analyte monograph[permanent dead link] - The Association for Clinical Biochemistry and Laboratory Medicine
  • Prof. David Spence on homocysteine levels, kidney damage, and cardiovascular disease, The Health Report, Radio National, 24 May 2010

October 14, 2023
homocysteine, confused, with, homocystine, proteinogenic, amino, acid, homologue, amino, acid, cysteine, differing, additional, methylene, bridge, biosynthesized, from, methionine, removal, terminal, methyl, group, body, homocysteine, recycled, into, methionin. Not to be confused with homocystine Homocysteine ˌ h oʊ m oʊ ˈ s ɪ s t iː n or Hcy is a non proteinogenic a amino acid It is a homologue of the amino acid cysteine differing by an additional methylene bridge CH2 It is biosynthesized from methionine by the removal of its terminal Ce methyl group In the body homocysteine can be recycled into methionine or converted into cysteine with the aid of vitamin B6 B9 and B12 3 Homocysteine NamesIUPAC name 2 Amino 4 sulfanylbutanoic acidIdentifiersCAS Number 454 29 5 racemate Y6027 13 0 L isomer Y3D model JSmol Interactive imageChEBI CHEBI 17230 YChEMBL ChEMBL310604 YChemSpider 757 YECHA InfoCard 100 006 567EC Number 207 222 9KEGG C05330 YPubChem CID 778UNII S7IJP4A89K racemate Y0LVT1QZ0BA L isomer YInChI InChI 1S C4H9NO2S c5 3 1 2 8 4 6 7 h3 8H 1 2 5H2 H 6 7 YKey FFFHZYDWPBMWHY UHFFFAOYSA N YInChI 1 C4H9NO2S c5 3 1 2 8 4 6 7 h3 8H 1 2 5H2 H 6 7 Key FFFHZYDWPBMWHY UHFFFAOYASSMILES C CS C C O O NPropertiesChemical formula C4H9NO2SMolar mass 135 18 g molAppearance White crystalline powderMelting point 234 235 C 453 455 F 507 508 K 2 decomposes Solubility in water solublelog P 2 56 1 Acidity pKa 2 25 1 HazardsGHS labelling PictogramsSignal word WarningHazard statements H302Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N verify what is Y N Infobox references High levels of homocysteine in the blood hyperhomocysteinemia is regarded as a marker of cardiovascular disease likely working through atherogenesis which can result in 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 arteries which supply the heart with oxygenated blood 4 5 Hyperhomocysteinemia has 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 6 Hyperhomocysteinemia also has been associated with early term spontaneous abortions 7 and with neural tube defects 8 Contents 1 Structure 2 Biosynthesis and biochemical roles 2 1 Biosynthesis of cysteine 2 2 Methionine salvage 2 3 Other reactions of biochemical significance 3 Homocysteine levels 4 Elevated homocysteine 5 References 6 External linksStructure Edit nbsp Zwitterionic form of S homocysteine left and R homocysteine right Homocysteine exists at neutral pH values as a zwitterion Biosynthesis and biochemical roles Edit nbsp 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 9 First methionine receives an adenosine group from ATP a reaction catalyzed by S adenosyl methionine synthetase to give S adenosyl methionine SAM e SAM e then transfers the methyl group to an acceptor molecule e g norepinephrine as an acceptor during epinephrine synthesis DNA methyltransferase as an intermediate acceptor in the process of DNA methylation The adenosine is then hydrolyzed to yield L homocysteine L Homocysteine has two primary fates conversion via tetrahydrofolate THF back into L methionine or conversion to L cysteine 10 Biosynthesis of cysteine Edit Mammals biosynthesize the amino acid cysteine via homocysteine Cystathionine b synthase catalyses the condensation of homocysteine and serine to give cystathionine This reaction uses pyridoxine vitamin B6 as a cofactor Cystathionine g lyase then converts this double amino acid to cysteine ammonia and a ketobutyrate Bacteria and plants rely on a different pathway to produce cysteine relying on O acetylserine 11 nbsp MTHFR metabolism folate cycle methionine cycle trans sulfuration and hyperhomocysteinemia 5 MTHF 5 methyltetrahydrofolate 5 10 methyltetrahydrofolate BAX Bcl 2 associated X protein BHMT betaine homocysteine S methyltransferase CBS cystathionine beta synthase CGL cystathionine gamma lyase DHF dihydrofolate vitamin B9 DMG dimethylglycine dTMP thymidine monophosphate dUMP deoxyuridine monophosphate FAD flavine adenine dicucleotide FTHF 10 formyltetrahydrofolate MS methionine synthase MTHFR mehtylenetetrahydrofolate reductase SAH S adenosyl L homocysteine SAME S adenosyl L methionine THF tetrahydrofolateMethionine salvage Edit Homocysteine can be recycled into methionine This process uses N5 methyl tetrahydrofolate as the methyl donor and cobalamin vitamin B12 related enzymes More detail on these enzymes can be found in the article for methionine synthase Other reactions of biochemical significance Edit Homocysteine can cyclize to give homocysteine thiolactone a five membered heterocycle Because of this self looping reaction homocysteine containing peptides tend to cleave themselves by reactions generating oxidative stress 12 Homocysteine also acts as an allosteric antagonist at Dopamine D2 receptors 13 It has been proposed that both homocysteine and its thiolactone may have played a significant role in the appearance of life on the early Earth 14 Homocysteine levels Edit nbsp Total plasma homocysteineHomocysteine levels typically are higher in men than women and increase with age 15 16 Common levels in Western populations are 10 to 12 mmol L and levels of 20 mmol L are found in populations with low B vitamin intakes or in the elderly e g Rotterdam Framingham 17 18 It is decreased with methyl folate trapping where it is accompanied by decreased methylmalonic acid increased folate and a decrease in formiminoglutamic acid 19 This is the opposite of MTHFR C677T mutations which result in an increase in homocysteine citation needed Blood reference ranges for homocysteine Sex Age Lower limit Upper limit Unit Elevated Therapeutic targetFemale 12 19 years 3 3 20 7 2 20 mmol L gt 10 4 mmol L or gt 140 mg dl lt 6 3 mmol L 21 or lt 85 mg dL 21 45 22 100 22 mg dL gt 60 years 4 9 20 11 6 20 mmol L66 22 160 22 mg dLMale 12 19 years 4 3 20 9 9 20 mmol L gt 11 4 mmol L or gt 150 mg dL60 22 130 22 mg dL gt 60 years 5 9 20 15 3 20 mmol L80 22 210 22 mg dLThe 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 EditMain article Hyperhomocysteinemia Abnormally high levels of homocysteine in the serum above 15 mmol L are a medical condition called hyperhomocysteinemia 23 This has been claimed to be a significant risk factor for the development of a wide range of diseases including thrombosis 24 neuropsychiatric illness 25 26 27 28 and fractures 29 30 It also is found to be associated with microalbuminuria which is a strong indicator of the risk of future cardiovascular disease and renal dysfunction 31 Vitamin B12 deficiency when coupled with high serum folate levels has been found to increase overall homocysteine concentrations as well 32 Typically hyperhomocysteinemia is managed with vitamin B6 vitamin B9 and vitamin B12 supplementation 33 However supplementation with these vitamins does not appear to improve cardiovascular disease outcomes 34 References Edit a b Chalcraft Kenneth R Lee Richard Mills Casandra Britz McKibbin Philip 2009 Virtual Quantification of Metabolites by Capillary Electrophoresis Electrospray Ionization Mass Spectrometry Predicting Ionization Efficiency Without Chemical Standards Analytical Chemistry 81 7 2506 2515 doi 10 1021 ac802272u PMID 19275147 Allen Milton J Steinman Harry G 1952 The Electrolytic Reduction of Homocystine at a Controlled Reference Potential Journal of the American Chemical Society 74 15 3932 3933 doi 10 1021 ja01135a502 Homocysteine PDF moh gov vn Retrieved 5 April 2023 Kim J Kim H Roh H Kwon Y 2018 Causes of hyperhomocysteinemia and its pathological significance Arch Pharm Res 41 4 372 383 doi 10 1007 s12272 018 1016 4 PMID 29552692 S2CID 3986295 a href Template Cite journal html title Template Cite journal cite journal a CS1 maint multiple names authors list link Boudi Brian F Noncoronary Atherosclerosis Medscape Archived from the original on 2013 05 11 Homocysteine The Facts Tufts Health and Nutrition Letter July 31 2020 update Nelen WL Blom HJ Steegers EA den Heijer M Thomas CM Eskes TK 2000 Homocysteine and folate levels as risk factors for recurrent early pregnancy loss Obstet Gynecol 95 4 519 24 doi 10 1016 s0029 7844 99 00610 9 PMID 10725483 S2CID 26125655 van der Put NJ et al Folate Homocysteine and Neural Tube Defects An Overview Archived 2015 09 16 at the Wayback Machine Exp Biol Med Maywood April 2001 vol 226 no 4 243 270 Selhub J 1999 Homocysteine metabolism Annual Review of Nutrition 19 217 246 doi 10 1146 annurev nutr 19 1 217 PMID 10448523 S2CID 2335090 Champe PC and Harvey RA Biochemistry Lippincott s Illustrated Reviews 4th ed Lippincott Williams and Wilkins 2008 Nelson D L Cox M M Lehninger Principles of Biochemistry 3rd Ed Worth Publishing New York 2000 ISBN 1 57259 153 6 Sibrian Vazquez M Escobedo JO Lim S Samoei GK Strongin RM January 2010 Homocystamides promote free radical and oxidative damage to proteins Proc Natl Acad Sci U S A 107 2 551 4 Bibcode 2010PNAS 107 551S doi 10 1073 pnas 0909737107 PMC 2818928 PMID 20080717 Agnati LF Ferre S Genedani S Leo G Guidolin D Filaferro M Carriba P Casado V Lluis C Franco R Woods AS Fuxe K Nov 2006 Allosteric modulation of dopamine D2 receptors by homocysteine PDF Journal of Proteome Research 5 11 3077 83 CiteSeerX 10 1 1 625 26 doi 10 1021 pr0601382 PMID 17081059 Archived PDF from the original on 2017 08 09 Vallee Yannick Shalayel Ibrahim Ly Kieu Dung Rao K V Raghavendra Paepe Gael De Marker Katharina Milet Anne 2017 11 08 At the very beginning of life on Earth the thiol rich peptide TRP world hypothesis International Journal of Developmental Biology 61 8 9 471 478 doi 10 1387 ijdb 170028yv ISSN 0214 6282 PMID 29139533 Nygard O 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1469 493X PMC 4164174 PMID 25590290 External links Edit nbsp Wikiversity has learning resources about Homocysteine Homocysteine MS Spectrum Homocysteine at Lab Tests Online Homocysteine analyte monograph permanent dead link The Association for Clinical Biochemistry and Laboratory Medicine Prof David Spence on homocysteine levels kidney damage and cardiovascular disease The Health Report Radio National 24 May 2010 Retrieved from https en wikipedia org w index php title Homocysteine amp oldid 1175851429, wikipedia, wiki, book, books, library,

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