Homocysteine

Homocysteine is a sulfur-containing amino acid produced during the metabolism of the essential amino acid methionine. It is not incorporated into proteins, but serves as an intermediate in two main pathways that recycle methionine or convert homocysteine to cysteine.

In remethylation, homocysteine is converted back to methionine by methionine synthase, with cofactors vitamin B12 and folate. In transsulfuration, cystathionine beta-synthase converts homocysteine to cystathionine, which is then further processed to cysteine; this reaction requires vitamin B6. Disruptions in these pathways, due to genetic variants or nutrient deficiencies, raise plasma homocysteine levels.

Measuring plasma homocysteine is common in research and some clinical settings. Typical reference ranges in adults are roughly 5–15 micromoles per liter (µmol/L). Levels can be influenced by age, sex, kidney function, smoking, alcohol use, and certain medications. Very high elevations occur in homocystinuria, a group of inherited metabolic disorders.

Clinical significance: elevated homocysteine is associated with higher risk of cardiovascular disease and stroke in observational studies, but whether lowering it reduces risk remains uncertain. Homocysteine may reflect underlying nutritional status and renal function rather than directly causing disease. Management focuses on correcting deficiencies with B vitamins, promoting a healthy diet, and addressing kidney disease; high-risk individuals may receive targeted dietary advice.

In classic homocystinuria, caused by cystathionine beta-synthase deficiency or other metabolic defects, treatment may include high-dose vitamin B6 in responsive patients, a low-methionine diet, and betaine to promote remethylation of homocysteine to methionine, along with regular monitoring.