Metabolic role of hyperhomocysteinemia in the etiology of chronic diseases

The significance of elevated blood homocysteine (Hcy) in clinical practice is a serious subject for researchers and is considered as a marker of certain diseases [1]. Hcy, is a sulfur containing, non-proteinogenic amino acid required for the growth of cells and tissues [2, 3]. It is produced exclusively from methionine (Met), an essential amino acid obtained from diet [4]. Hcy is normally present in human plasma at lower concentrations. The normal range is reported to be 5-15 micromol/L [5]. The level could be affected by health-related behaviours, including diet, excessive coffee intake, alcohol consumption, cigarette smoking, and sedentary lifestyle [6, 7]. Total plasma Hcy could be in the form of free Hcy, protein-bound Hcy, oxidized forms of Hcy, and Hcy-thiolactone [3]. This is used as a predictive risk factor for stroke progression, cardiovascular disorders, test for vitamin B12 deficiency, and screening for inborn errors of Met metabolism. An increase of Hcy is referred to as hyperhomocysteinemia (HHcy) which is a sensitive marker of folate and vitamin B 12 deficiency and is associated with an increased risk of cardiovascular disease (CVD), pregnancy complications, cognitive impairment, stoke, and other diseases [8-10]. Plasma levels between 15 and 30 micromol/L are referred as mild HHcy, whereas levels between 31 and 100 micromol/L are moderate HHcy and levels above 100 micromol/L are described as severe HHcy [11]. There are also other studies which report that HHcy are associated with atherosclerosis, thrombosis, birth defects, osteoporosis, diabetes, and renal disease [2]. It is also reported to be highly prevalent in chronic kidney disease (CKD) patients. There are several risk factors that could lead to HHcy- the main cause being insufficient intake of vitamin B group especially folic acid (B9), pyridoxine (B6), or B12 (cyanocobalamin), and several polymorphisms involved in methionine (Met) metabolism [9]. This could also lead to high excretion of Hcy (oxidized Hcy) in urine (homocystinuria) [12]. The relation between HHcy and morphological changes in the organs are extremely important to improve the diagnostic methods and to develop effective treatment.