M. Malinow
Jun 1, 1990
Citations
1
Influential Citations
275
Citations
Quality indicators
Journal
Circulation
Abstract
H omocysteine (HCY) is a thiol-containing amino acid that results from the demethylation of methionine. HCY is readily oxidized in body fluids to the disulfides homocystine (HCY-HCY) and HCY-cysteine (CYS) mixed disulfide (MDS) (see Figure 1). Free and protein-bound forms in plasma are collectively designated homocyst(e)ine [H(e)], and their total concentration is expressed as HCY in nanomoles per milliliter (i.e., micromoles per liter). The normal concentration of H(e) in plasma is -10 nmol/ml, but it may attain levels of 200 nmol/ml in homocystinuria. This rare genetic condition is usually associated with serious thromboembolic complications at an early age; thrombosis of extracranial and intracranial arteries, veins, and sinuses as well as coronary occlusion are common fatal occurrences. In young homocystinuric patients, occlusion of peripheral arteries often results in renovascular hypertension, intermittent claudication, or mesenteric ischemia, and peripheral venous thrombosis may be followed by pulmonary embolism. Premature arteriosclerotic lesions in most large and medium-sized arteries are common in these patients (i.e., thickened intima resulting in narrowing of the vascular lumen with microscopic intimal fibrosis and often disruption, fragmentation, and thickening of elastic fibers). Patients may also exhibit mental retardation as well as other abnormalities resembling the unrelated Marfan's syndrome (i.e., ectopia lentis and skeletal deformitiesl"2). Several abnormalities in single enzymes controlling the metabolism of HCY have been described in homocystinuric subjects,1-6 mainly, impairment of cystathionine ,B-synthase -which regulates an early step in the transsulfuration of HCY to CYS -and of 5,10 -methylenetetrahydrofolate reductase, which provides substrate for the B-12dependent remethylation of HCY to methionine.