Potential role of functional foods and antioxidants in relation to oxidative stress and hyperhomocysteinemia

Abstract

Homocysteine (Hcy) is a non-essential sulfur-containing amino acid that is derived from the metabolism of methionine, an essential amino acid [1, 2]. Homocysteine is present in the plasma of healthy individuals (3-10 μM) and physiologically is produced in all cells but when homocysteine is elevated in plasma hyperhomocysteinemia (HHCy) is occurred. Hyperhomocysteinemia, which is common in the elderly, is caused by rare genetic mutations (cystathionine-B-synthase, methylenetetrahydrofolate reductase). The amount of homocysteine in mild to moderate hyperhomocysteinemia is 10-100 μM and in severe hyperhomocysteinemia is 100-200 μM [2]. Several factors can lead to hyperhomocysteinemia. It can be an inborn error, due to inherited metabolic disorders, or acquired [1]. Deficiencies of the cofactors vitamins B6, folate, and B12, drugs that interfere with cofactor metabolism, disorders such as hypothyroidism, renal failure, neurological and cardiovascular diseases, aging, and lifestyle factors such as diet, physical inactivity, alcohol, and smoking are among the acquired causes of moderate elevation of plasma homocysteine [3]. Homocystinuria is an autosomal recessive disorder and is associated with the accumulation of homocysteine and methionine in biological fluids and high urinary homocysteine excretion. The disease is a congenital disorder in the metabolism of amino acid, which is usually caused by a deficiency in the activity of the cystathionine ß-synthase enzyme. Transsulfuration of homocysteine to cystathionine is catalyzed by the cystathionine ß-synthase with the help of its cofactor pyridoxine. Two different forms of cystathionine ß-synthase deficiency have existed including pyridoxine-responsive and pyridoxine-nonresponsive. Mutations inactivating the methylenetetrahydrofolate reductase and methionine synthase enzymes are other genetic defects that might increase plasma homocysteine concentrations [3].