Homocysteine and Folic Acid Metabolism

Abstract

Homocysteine (Hcy) and folate metabolism plays a crucial role in maintaining the overall human health. Hcy is a non-proteinogenic amino acid synthesized from methionine with the involvement of some methyl group donor intermediates. The metabolism of homocysteine involves three pivotal processes: S-adenosyl-L-methionine (SAM)-dependent transmethylation, folate-dependent or -independent remethylation cycles, and transsulfuration reactions. The entire metabolic pathway is governed by various endogenous and exogenous factors including the genetic composition (polymorphism in MTHFR, GCP2, RFC1, and TCN2 genes) and the diet intake (methionine and cysteine richness of constituents) of an organism. Additionally, the concentrations of intermediates (AdoMet, AdoHcy, and methylTHF) and enzymes (GAMT, PEMT, GNMT, BHMT, MS, and CBS) involved in these reactions regulate the process at the cellular level. Folate, an intermediate produced during the homocysteine metabolism, is involved in numerous other metabolic pathways, which are associated with neural development, reproductive, renal and cardiovascular health of humans. The aberrantly altered level of homocysteine (commonly hyperhomocysteinemia) triggers various pathological symptoms and subsequently the Hcy-related diseases. Increased plasma homocysteine concentrations could lead to hyperhomocysteinemia which is a risk factor for several pathologies such as cardiovascular diseases (CVD), and is also related to early atherosclerosis symptoms and venous thrombosis. Further, the elevated level of homocysteine is associated with other pathologies like autoimmune responses (diabetes I and diabetes II), neural development (neural tube defects), neurodegenerative diseases, and reproductive health as male and female infertility. © The Editor(s) (if applicable) and The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2022.