Homocystein

Homocysteine, sometimes spelled homocystein in non-English texts, is a sulfur-containing amino acid produced during the metabolism of methionine. It is not incorporated into proteins and exists primarily as a free amino acid in blood plasma.

Biochemical role and metabolism: Methionine is converted to S-adenosylmethionine (SAM), a universal methyl donor. After donating its methyl group, SAM becomes S-adenosylhomocysteine and then homocysteine. Homocysteine can be remethylated to methionine by methionine synthase (requiring 5-methyl-tetrahydrofolate and vitamin B12) or by betaine-homocysteine methyltransferase (using betaine). Alternatively, it enters transsulfuration to cystathionine via cystathionine beta-synthase (requiring vitamin B6), leading to cysteine synthesis.

Normal levels and contributing factors: Fasting plasma homocysteine is typically about 5–15 µmol/L. Elevated levels can result from deficiencies of folate, vitamin B6, or vitamin B12, kidney disease, hypothyroidism, certain medications, age, and genetic defects in remethylation or transsulfuration pathways.

Clinical significance: Mild to moderate hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, stroke, and venous thromboembolism, though causality and the benefits of lowering levels are topics of ongoing research. In pregnancy, high homocysteine is linked with neural tube defects and other complications. A rare inherited disorder, homocystinuria, usually due to cystathionine beta-synthase deficiency or remethylation defects, causes markedly elevated homocysteine with lens dislocation, skeletal abnormalities, developmental delay, and thromboembolism.

Diagnosis and management: Plasma homocysteine measurement is used in evaluation. Management focuses on correcting nutritional deficiencies (folate, B6, B12) and, in homocystinuria, disease-specific therapies. Lowering homocysteine with B vitamins reduces levels in many individuals, but cardiovascular outcome benefits are variable.