Biomarkers

Target: Homocysteine

Homocysteine (CAS: 454-29-5) is a sulfur-containing amino acid that arises during methionine metabolism. Although its concentration in plasma is only about 10 micromolar (uM), even moderate hyperhomocysteinemia is associated with an increased incidence of cardiovascular disease and Alzheimer's disease. Elevations in plasma homocysteine are commonly found as a result of vitamin deficiencies, polymorphisms of enzymes of methionine metabolism, and renal disease. It has been identified as a uremic toxin according to the European Uremic Toxin Working Group (PMID: 22626821 ). Pyridoxal, folic acid, riboflavin, and vitamin B(12) are all required for methionine metabolism, and deficiency of each of these vitamins result in elevated plasma homocysteine. A polymorphism of methylenetetrahydrofolate reductase (C677T), which is quite common in most populations with a homozygosity rate of 10-15 %, is associated with moderate hyperhomocysteinemia, especially in the context of marginal folate intake. Plasma homocysteine is inversely related to plasma creatinine in patients with renal disease. This is due to an impairment in homocysteine removal in renal disease. The role of these factors, and of modifiable lifestyle factors, in affecting methionine metabolism and in determining plasma homocysteine levels is discussed. Homocysteine is an independent cardiovascular disease (CVD) risk factor modifiable by nutrition and possibly exercise. Homocysteine was first identified as an important biological compound in 1932 and linked with human disease in 1962 when elevated urinary homocysteine levels were found in children with mental retardation. This condition, called homocystinuria, was later associated with premature occlusive CVD, even in children. Specifically, in adults (>18 years old) with homocystinuria, homocysteine is shown to be reduced in the blood at a concentration of 6.00 (4.8-7.40) μM (MetaGene) compared to normal adults at a concentration of 9.8 (7.6-14.9) μM (PMID: 11380830). These observations led to research investigating the relationship of elevated homocysteine levels and CVD in a wide variety of populations including middle age and elderly men and women with and without traditional risk factors for CVD (PMID: 17136938 , 15630149 ). Moreover, homocysteine is found to be associated with cystathionine beta-synthase deficiency, cystathioninuria, methylenetetrahydrofolate reductase deficiency, and sulfite oxidase deficiency, which are inborn errors of metabolism. In children (1-13 years old) with cystathionine beta-synthase deficiency, homocysteine in the blood is significantly elevated at a concentration of 125.00 (50.00-200.00) μM (MetaGene) compared to normal children at a concentration of 10.4 +/- 2.3 μM (PMID: 9554495). Similarly, in children (1-13 years old) with cystathioninuria, homocysteine is significantly elevated in the blood at a concentration of 20.5 μM (PMID: 20584029) compared to normal children at a concentration of 10.4 +/- 2.3 μM (PMID: 9554495). In adults (>18 years old) with methylenetetrahydrofolate reductase deficiency, homocysteine is elevated in the blood at a concentration of 180 μM (PMID: 8456826) compared to normal adults at a concentration of <20 μM (PMID: 8456826).