An elevated plasma concentration of total homocysteine (tHcy) is a risk factor for cardiac disease, stroke, vascular dementia, Alzheimer disease, and depression.1,2 This may reflect a toxic effect of elevated tHcy, perhaps by free radical formation or inhibition of particular enzymes, or, alternatively, elevated tHcy may be a marker of disrupted 1-carbon metabolism.3 As shown in Figure 1, methylation of multiple intracellular molecules, including nucleic acids and proteins, uses S-adenosylmethionine (SAM) as the donor, which is converted to S-adenosylhomocysteine (SAH), which is in equilibrium with homocysteine. The regeneration of methionine, the precursor of SAM, occurs in neurons exclusively via methionine synthase, which requires methyltetrahydrofolate and vitamin B12. Additionally, vitamin B6 deficiency results in tHcy elevation by preventing the conversion by cystathionine β-synthase of homocysteine to cystathionine.
O'Suilleabhain P, Diaz-Arrastia R. Levodopa Elevates Homocysteine: Is This a Problem? Arch Neurol. 2004;61(5):633–634. doi:10.1001/archneur.61.5.633
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