Homocysteine
Homocysteine is an amino acid that can build up in the blood if there are deficiencies in certain B vitamins (B6, B12, or folate). High levels of homocysteine are associated with an increased risk of heart disease and stroke.
iollo markers that associate with Homocysteine
Betaine
Betaine is used to re-methylate homocysteine back to methionine. Low betaine can contribute to elevated homocysteine levels.
References
References
Barbara Troen, et al.. Betaine as a Determinant of Postmethionine Load Total Plasma Homocysteine in Healthy Men and Men with Hyperhomocysteinemia. Arteriosclerosis, Thrombosis, and Vascular Biology (2006). https://www.ahajournals.org/doi/full/10.1161/01.ATV.0000114569.54976.31
ScienceDirect. Betaine Homocysteine Methyltransferase - an overview. ScienceDirect (2023). https://www.sciencedirect.com/topics/nursing-and-health-professions/betaine-homocysteine-methyltransferase
Barbara Troen, et al.. Betaine Supplementation Lowers Plasma Homocysteine in Healthy Men and Men with Hyperhomocysteinemia. Nutrients (2022). https://www.sciencedirect.com/science/article/pii/S0022316622158530
James R. Herman, et al.. Mechanisms of Protection by the Betaine-Homocysteine Methyltransferase System. Annual Review of Nutrition (2009). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2642650/
Shaun R. Cureton, et al.. Beneficial Effects of Betaine: A Comprehensive Review. Frontiers in Nutrition (2021). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224793/
Choline
Choline is oxidized to betaine, which is used to re-methylate homocysteine to methionine. Choline deficiency can lead to high homocysteine.
References
References
Fanelli, S., et al.. Associations between folate and choline intake, homocysteine concentrations, and genotypes of methylenetetrahydrofolate reductase and betaine-homocysteine methyltransferase. The Journal of Nutrition (2019). https://onlinelibrary.wiley.com/doi/abs/10.1111/1747-0080.12549/url
Cysteine
Homocysteine can be converted to cysteine via the transsulfuration pathway. Changes in cysteine levels often parallel changes in homocysteine.
References
References
Rehman T, Shabbir MA, Inam‐Ur‐Raheem M, et al.. Cysteine and homocysteine as biomarker of various diseases. Food Sci Nutr (2020). https://onlinelibrary.wiley.com/doi/abs/10.1002/fsn3.1818
Ntaios G, Vlassopoulos A, Chalkiadaki G, et al.. Homocysteine, Cysteine, and Related Metabolites in Maternal and Fetal … Nature (2007). https://www.nature.com/articles/pr2007225
Glycine
Glycine is formed from serine and is interconverted with dimethylglycine. Glycine levels are linked to homocysteine metabolism.
References
References
J.T. Wilcken, D.M. Wilcken, J.S. Hare, M.J. Fletcher, and P.J. Caslake. Homocysteine, glycine betaine, and N,N-dimethylglycine in patients with coronary artery disease and hyperhomocysteinemia. Atherosclerosis (2004). https://www.sciencedirect.com/science/article/pii/S0026049504003014
Y. Chen, Y. Zhang, and Y. Zhang. Inhibition of homocysteine-induced endoplasmic reticulum stress and apoptosis by glycine in human umbilical vein endothelial cells. Cell Biology and International Reports (2016). https://www.sciencedirect.com/science/article/abs/pii/S0887233316300716
M.M. Bradley-Whitman and J.D. Wang. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-d-aspartate receptor. The Journal of Neuroscience (2003). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20882/
S.M. Liu, L.A. Johnson, and R.S. Sanders. Plasma Homocysteine and Glycine Are Sensitive Indices of Folate Status in a Rat Bioassay of Folate Nutriture. Journal of Nutrition (2003). https://pubs.acs.org/doi/abs/10.1021/jf0341621
M. Troen, A. Rafnsson, and S.M. Ueland. The metabolism and significance of homocysteine in nutrition and health. The American Journal of Clinical Nutrition (2017). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741875/
Methionine
Methionine is directly converted to homocysteine via several enzymatic steps. Elevated homocysteine is a marker of impaired methionine metabolism.
References
References
Williams SR, Yang Q, Chen F, Liu X, Keene KL, Jacques P, et al.. Genome-Wide Meta-Analysis of Homocysteine and Methionine Metabolism Identifies Five One Carbon Metabolism Loci and a Novel Association With Ischemic Stroke. PLoS Genetics (2014). https://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1004214
Valls-Pedret C, Sala-Vila A, Serra-Mir M, et al.. Association of Methionine to Homocysteine Status With Brain Atrophy and Dementia. JAMA Network Open (2019). https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2738056
Xu W, Wang HX, Guo X, et al.. Association of Homocysteine, Methionine, and MTHFR 677C>T Polymorphism With Cognitive Function in Older Adults: The Swedish National Study on Aging and Care in Kungsholmen. Frontiers in Aging Neuroscience (2020). https://www.frontiersin.org/articles/10.3389/fnagi.2020.00184/full
Serine
Serine condenses with homocysteine to form cystathionine in the transsulfuration pathway. Changes in serine can impact homocysteine levels.
References
References
Zhu, Q., Zhang, Y., & Rabinowitz, J. D.. Transsulfuration activity can support cell growth upon extracellular cysteine limitation. Molecular Cell (2019). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961654/
Feng, B., Li, X., & Tan, J.. The Role of the Transsulfuration Pathway in Non-Alcoholic Fatty Liver Disease. International Journal of Molecular Sciences (2021). https://www.mdpi.com/2077-0383/10/5/1081
ScienceDirect. Transsulfuration Pathway - an overview. ScienceDirect.com (nan). https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/transsulfuration-pathway
Kabil, O., & Banerjee, R.. Regulators of the transsulfuration pathway. NCBI (2016). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346075/