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.
Choline is oxidized to betaine, which is used to re-methylate homocysteine to methionine. Choline deficiency can lead to high homocysteine.
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
Glycine is formed from serine and is interconverted with dimethylglycine. Glycine levels are linked to homocysteine metabolism.
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/S0026049504003014Y. 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/S0887233316300716M.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/jf0341621M. 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 is directly converted to homocysteine via several enzymatic steps. Elevated homocysteine is a marker of impaired methionine metabolism.
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.1004214Valls-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/2738056Xu 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