Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Oct 20;17(10):1733.
doi: 10.3390/ijms17101733.

The Molecular and Cellular Effect of Homocysteine Metabolism Imbalance on Human Health

Henrieta Škovierová  1 , Eva Vidomanová  2 , Silvia Mahmood  3 , Janka Sopková  4   5 , Anna Drgová  6   7 , Tatiana Červeňová  8 , Erika Halašová  9   10 , Ján Lehotský  11   12
Affiliations
Review

The Molecular and Cellular Effect of Homocysteine Metabolism Imbalance on Human Health

Henrieta Škovierová et al. Int J Mol Sci. .

Abstract

Homocysteine (Hcy) is a sulfur-containing non-proteinogenic amino acid derived in methionine metabolism. The increased level of Hcy in plasma, hyperhomocysteinemia, is considered to be an independent risk factor for cardio and cerebrovascular diseases. However, it is still not clear if Hcy is a marker or a causative agent of diseases. More and more research data suggest that Hcy is an important indicator for overall health status. This review represents the current understanding of molecular mechanism of Hcy metabolism and its link to hyperhomocysteinemia-related pathologies in humans. The aberrant Hcy metabolism could lead to the redox imbalance and oxidative stress resulting in elevated protein, nucleic acid and carbohydrate oxidation and lipoperoxidation, products known to be involved in cytotoxicity. Additionally, we examine the role of Hcy in thiolation of proteins, which results in their molecular and functional modifications. We also highlight the relationship between the imbalance in Hcy metabolism and pathogenesis of diseases, such as cardiovascular diseases, neurological and psychiatric disorders, chronic kidney disease, bone tissue damages, gastrointestinal disorders, cancer, and congenital defects.

Keywords: cellular toxicity; disease; homocysteine metabolism; hyperhomocysteimenia; oxidative stress.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The schematic overview of homocysteine metabolism and its relationship with folic acid and vitamins. ATP: adenosine triphosphate; AMP: adenosine monophosphate; PPi: pyrophosphate; Pi: orthophosphate; B2/B6/B12: vitamins B2/B6/B12; CoA: coenzyme A; R: acceptor; R-CH3: methylated product; MT: methyltransferases.
Figure 2
Figure 2
The structure of methionine, homocysteine, homocysteine-thiolactone (homocysteine-TL; Hcy-TL) and N-/S-homocysteinylation of proteins. Methionine is metabolized to homocysteine which should be subsequently catalyzed to Hcy-TL by methionyl t-RNA synthetase. Hcy-TL modifies proteins by N-homocyteinylation. On the other hand, Hcy could bind to cysteine residues of a protein to make disulfide bound resulted in S-homocysteinylation of proteins.
See this image and copyright information in PMC

References

    1. Warnecke P.M., Bestor T.H. Cytosine methylation and human cancer. Curr. Opin. Oncol. 2000;12:68–73. doi: 10.1097/00001622-200001000-00012. - DOI - PubMed
    1. Stirzaker C., Song J.Z., Ng W., Du Q., Armstrong N.J., Locke W.J., Statham A.L., French H., Pidsley R., Valdes-Mora F., et al. Methyl-CpG-binding protein MBD2 plays a key role in maintenance and spread of DNA methylation at CpG islands and shores in cancer. Oncogen. 2016 doi: 10.1038/onc.2016.297. - DOI - PubMed
    1. Mudd S.H., Ebert M.H., Scriver C.R. Labile methyl group balances in the human: The role of sarcosine. Metabolism. 1980;29:707–720. doi: 10.1016/0026-0495(80)90192-4. - DOI - PubMed
    1. Stead L.M., Au K.P., Jacobs R.L., Brosnan M.E., Brosnan J.T. Methylation demand and homocysteine metabolism: Effects of dietary provision of creatine and guanidinoacetate. Am. J. Physiol. Endocrinol. Metab. 2001;281:E1095–E1100. doi: 10.1016/j.advenzreg.2003.11.012. - DOI - PubMed
    1. Jacobs R.L., Stead L.M., Devlin C., Tabas I., Brosnan M.E., Brosnan J.T., Vance D.E. Physiological regulation of phospholipid methylation alters plasma homocysteine in mice. J. Biol. Chem. 2005;280:28299–28305. doi: 10.1074/jbc.M501971200. - DOI - PubMed

LinkOut - more resources