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Homocysteine metabolism, hyperhomocysteinaemia and vascular disease: An overview

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  • Published:
Journal of Inherited Metabolic Disease

Summary

Hyperhomocysteinaemia has been regarded as a new modifiable risk factor for atherosclerosis and vascular disease. Homocysteine is a branch-point intermediate of methionine metabolism, which can be further metabolised via two alternative pathways: degraded irreversibly through the transsulphuration pathway or remethylated to methionine by the remethylation pathway. Both pathways are B-vitamin-dependent. Plasma homocysteine concentrations are determined by nongenetic and genetic factors. The metabolism of homocysteine, the role of B vitamins and the contribution of nongenetic and genetic determinants of homocysteine concentrations are reviewed. The mechanisms whereby homocysteine causes endothelial damage and vascular disease are not fully understood. Recently, a link has been postulated between homocysteine, or its intermediates, and an alterated DNA methylation pattern. The involvement of epigenetic mechanisms in the context of homocysteine and atherosclerosis, due to inhibition of transmethylation reactions, is briefly overviewed.

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Authors and Affiliations

  1. Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa, Av. Prof. Gama Pinto, Lisbon, 1649-003, Portugal

    R. Castro, I. Rivera & I. Tavares de Almeida

  2. Department of Paediatrics, University Medical Center, St. Radboud, Nijmegen, The Netherlands

    H. J. Blom

  3. Metabolic Unit, Department of Clinical Chemistry, VU University Medical Centre, Amsterdam, The Netherlands

    C. Jakobs

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  1. R. Castro
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  2. I. Rivera
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Castro, R., Rivera, I., Blom, H.J. et al. Homocysteine metabolism, hyperhomocysteinaemia and vascular disease: An overview. J Inherit Metab Dis 29, 3–20 (2006). https://doi.org/10.1007/s10545-006-0106-5

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