Overview of homocysteine and its role in disease processes
DOI:
https://doi.org/10.12775/QS.2025.41.60254Keywords
Homocysteine, cardiovascular diseases, homocysteine metabolism, hiperhomocysteinemia, Neurodegeneration, Cognitive diseasesAbstract
Homocysteine is a sulfur-containing amino acid formed from the essential amino acid methionine. This metabolism cycle requires vitamin-derived cofactors, pyridoxine for transsulfuration and both folate and cobalamin [1]. In a normal diet there is conservation of the carbon skeleton, and about 50% of the homocysteine formed is remethylated to methionine via steps that require folic acid and vitamin B12. A deficiency of any of these three vitamins leads to modest homocysteine elevation. Why does hyperhomocysteinemia play a vital role in medical practice? It is established that homocysteine elevation is associated with different complications, mainly increased cardiovascular risk [2]. Hyperhomocysteinemia and homocystinuria is connected with occlusive artery disease, especially in the brain, the heart, and the kidney, in addition to venous thrombosis. However the increased level of homocysteine has also an impact on other systems and is connected with osteoporosis, depression, Alzheimer's disease, pregnancy problems, and others. Elevated homocysteine levels occur in both the adult and child population [3].
This review article will address the importance of homocysteine in nervous and cardiovascular systems but also indicate some controversial theses and reasons to further investigation.
References
1. James D Finkelstein, John J Martin. Homocysteine. The International Journal of Biochemistry & Cell Biology, Volume 32, Issue 4, 2000, doi: 10.1016/s1357-2725(99)00138-7
2. DAVID E. L. WILCKEN, BRIDGET WILCKEN. B Vitamins and Homocysteine in Cardiovascular Disease and Aging. Annals of the New York Academy of SciencesVolume 854, Issue 1. doi: 10.1111/j.1749-6632.1998.tb09916.x
3. Zaric BL, Obradovic M, Bajic V, Haidara MA, Jovanovic M, Isenovic ER. Homocysteine and Hyperhomocysteinaemia. Curr Med Chem. 2019;26(16):2948-2961. doi: 10.2174/0929867325666180313105949. PMID: 29532755.
4. Faeh D, Chiolero A, Paccaud F. Homocysteine as a risk factor for cardiovascular disease: should we (still) worry about? Swiss Med Wkly. 2006 Dec 2;136(47-48):745-56. doi: 10.4414/smw.2006.11283. PMID: 17225194.
5. Loscalzo J, Handy DE. Epigenetic modifications: basic mechanisms and role in cardiovascular disease (2013 Grover Conference series). Pulm Circ. 2014 Jun;4(2):169-74. doi: 10.1086/675979. PMID: 25006435; PMCID: PMC4070783.
6. Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015 Jan 10;14:6. doi: 10.1186/1475-2891-14-6. PMID: 25577237; PMCID: PMC4326479.
7. Guo H, Chi J, Xing Y, Wang P. Influence of folic acid on plasma homocysteine levels & arterial endothelial function in patients with unstable angina. Indian J Med Res. 2009 Mar;129(3):279-84. PMID: 19491420.
8. Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet. 1999 Jul 31;354(9176):407-13. doi: 10.1016/S0140-6736(98)11058-9. PMID: 10437885.
9. Alkaissi H, McFarlane SI. Hyperhomocysteinemia and Accelerated Aging: The Pathogenic Role of Increased Homocysteine in Atherosclerosis, Osteoporosis, and Neurodegeneration. Cureus. 2023 Jul 21;15(7):e42259. doi: 10.7759/cureus.42259. PMID: 37605676; PMCID: PMC10440097.
10. Smulders YM, Blom HJ. The homocysteine controversy. J Inherit Metab Dis. 2011 Feb;34(1):93-9. doi: 10.1007/s10545-010-9151-1. Epub 2010 Jun 22. PMID: 20567905; PMCID: PMC3026670.
11. Zhang S, Bai YY, Luo LM, Xiao WK, Wu HM, Ye P. Association between serum homocysteine and arterial stiffness in elderly: a community-based study. J Geriatr Cardiol. 2014 Mar;11(1):32-8. doi: 10.3969/j.issn.1671-5411.2014.01.007. PMID: 24748879; PMCID: PMC3981981.
12. Pang X, Liu J, Zhao J, Mao J, Zhang X, Feng L, Han C, Li M, Wang S, Wu D. Homocysteine induces the expression of C-reactive protein via NMDAr-ROS-MAPK-NF-κB signal pathway in rat vascular smooth muscle cells. Atherosclerosis. 2014 Sep;236(1):73-81. doi: 10.1016/j.atherosclerosis.2014.06.021. Epub 2014 Jun 28. PMID: 25016361.
13. Currò, M., Gugliandolo, A., Gangemi, C. et al. Toxic Effects of Mildly Elevated Homocysteine Concentrations in Neuronal-Like Cells. Neurochem Res 39, 1485–1495 (2014). https://doi.org/10.1007/s11064-014-1338-7
14. Moretti, R.; Giuffré, M.; Caruso, P.; Gazzin, S.; Tiribelli, C. Homocysteine in Neurology: A Possible Contributing Factor to Small Vessel Disease. Int. J. Mol. Sci. 2021, 22, 2051. https://doi.org/10.3390/ijms22042051
15. MDPI and ACS Style
Hermann, A.; Sitdikova, G. Homocysteine: Biochemistry, Molecular Biology and Role in Disease. Biomolecules 2021, 11, 737. https://doi.org/10.3390/biom11050737
16. Lehotský J, Tothová B, Kovalská M, Dobrota D, Beňová A, Kalenská D, Kaplán P. Role of Homocysteine in the Ischemic Stroke and Development of Ischemic Tolerance. Front Neurosci. 2016 Nov 23;10:538. doi: 10.3389/fnins.2016.00538. PMID: 27932944; PMCID: PMC5120102.
17. Lin WZ, Yu D, Xiong LY, Zebarth J, Wang R, Fischer CE, Rajji TK, Tang-Wai DF, Tartaglia C, Saposnik G, Swartz RH, Grimes DA, Lang AE, Hegele RA, Farhan S, Ramirez J, Symons S, Goubran M, Binns MA, Lou W, Dixon RA, Orange JB, Roberts AC, Troyer AK, Zetterberg H, Herrmann N, Rabin JS, MacIntosh BJ, Masellis M, Lanctôt KL, Black SE, Swardfager W; ONDRI Investigators. Homocysteine, neurodegenerative biomarkers, and APOE ε4 in neurodegenerative diseases. Alzheimers Dement. 2025 Jan;21(1):e14376. doi: 10.1002/alz.14376. Epub 2024 Nov 19. PMID: 39559926; PMCID: PMC11775453.
18. González-Lamuño D, Arrieta-Blanco FJ, Fuentes ED, Forga-Visa MT, Morales-Conejo M, Peña-Quintana L, Vitoria-Miñana I. Hyperhomocysteinemia in Adult Patients: A Treatable Metabolic Condition. Nutrients. 2023 Dec 30;16(1):135. doi: 10.3390/nu16010135. PMID: 38201964; PMCID: PMC10780827.
19. Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999;19:217-46. doi: 10.1146/annurev.nutr.19.1.217. PMID: 10448523.
20. Moretti, R.; Caruso, P. The Controversial Role of Homocysteine in Neurology: From Labs to Clinical Practice. Int. J. Mol. Sci. 2019, 20, 231. https://doi.org/10.3390/ijms20010231
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