Review Article Open Access Tripathi, Biochem Anal Biochem 2015, 4:4 DOI: 10.4172/2161-1009.1000237 Volume 4 • Issue 4 • 1000237 Biochem Anal Biochem ISSN: 2161-1009 Biochem, an open access journal Keywords: Metabolic disorders; Homocysteine; Renal dysfunction; Methylenetetrahydrofolate reductase; folic acid Introduction Homocysteine also known as the H-factor, is a naturally occurring amino acid and is a by-product of methionine metabolism in the body. It is a common amino acid (one of the building blocks that make up proteins) found in the blood and is acquired mostly from eating meat. In 1969, a connection between homocysteine (a sulfur-containing amino acid) and cardiovascular disease was proposed when it was observed that people with a rare hereditary condition called homocystinuria are prone to develop severe cardiovascular disease in their teens and twenties. In this condition, an enzyme defciency causes homocysteine to accumulate in the blood and to be excreted in the urine. Abnormal homocysteine elevation also occurs among people whose diet contains inadequate amounts of folic acid, vitamin B6, or vitamin B12. Regardless of the cause of the elevation, supplementation with one or more of these vitamins can lower plasma homocysteine levels. Studies done in the 1980s and 1990s linked elevated blood levels of homocysteine to increased risk of premature coronary artery disease, stroke, and venous blood clots, even among people with normal cholesterol levels [1,2]. Tese studies led to speculations that high homocysteine levels could contribute to atherosclerosis in at least three ways: (a) a direct toxic efect that damages the cells lining the inside of the arteries, (b) interference with clotting factors, and (c) oxidation of low-density lipoproteins (LDL). Homocysteine is a hidden toxic chemical that is not meant to accumulate unchecked in the body. It needs to be transformed into safer amino acids, like methionine and cysteine. Homocysteine levels increases in the plasma due to some metabolic problems that can be inherited or can result from nutritional defciencies and is known to be a major risk factor for atherosclerosis, coronary heart disease, stroke and Alzheimer’s disease [3,4]. Blood levels of homocysteine tend to be highest in people who eat a lot of animal protein and consume few fruits and leafy vegetables, which provide the folic acid and other B vitamins that help the body rid itself of homocysteine [5]. Homocysteine pathways normally lead to the production of other essentials including glutathione a powerful detoxifer and various hormones like serotonin (the happy hormone), melatonin (sleep and mood improving hormone), dopamine (euphoria hormone) and adrenaline (the fght and fight hormone).  *Corresponding author: Pratima Tripathi, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Anantapur- 515001 Andhra Pradesh, India, Tel: +91 8555 287239; E-mail: pratimatripathi.lko@gmail.com, pratimatripathi@sssihl.edu.in Received: November 28, 2015; Accepted: December 28, 2015; Published December 31, 2015 Citation: Tripathi P (2015) Homocysteine- The Hidden Factor and Cardiovascular Disease: Cause or Effect? Biochem Anal Biochem 4: 237. doi:10.4172/2161- 1009.1000237 Copyright: © 2015 Tripathi P. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Markedly or mildly elevated circulating homocysteine concentrations are associated with increased risk of vascular occlusion. Here we review possible mechanisms that mediate these effects. Inborn errors of homocysteine metabolism result in markedly elevated plasma homocysteine (200-300 μmol/L) and thromboembolic (mainly venous) disease which is easily normalized with oral folate and ongoing trials are assessing the effect of folate treatment on outcomes. Some people have a common genetic variant (called methylenetetrahydrofolate reductase, abbreviated MTHFR) that also impairs their ability to process folate. Indeed, there are evidences suggesting an acute antioxidant effect of folic acid on homocysteine concentrations. This antioxidant mechanism may oppose an oxidant effect of homocysteine and be relevant to treatment of patients with vascular disease, especially those with chronic renal insuffciency. Such patients have moderately elevated plasma homocysteine and greatly increased cardiovascular risk that is largely unexplained. Homocysteine- The Hidden Factor and Cardiovascular Disease: Cause or Effect? Pratima Tripathi* Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Anantapur- 515001 Andhra Pradesh, India Homocysteine is present in plasma in four diferent forms: around 1% circulates as free thiol, 70-80% remains disulphide-bound to plasma proteins, mainly albumin and 20-30% combines with itself to form the dimer homocysteine or with other thiols [6]. Homocysteine is a key determinant of the methylation cycle [7]. It is methylated to methionine, which undergoes S-adenosylation and forms S-adenosylmethionine (SAM) [7]. S- adenosylmethionine is the principal methyl donor for all methylation reactions in cells [7]. Condensation of methionine with ATP, leads to the formation of SAM (S- Adenosylmethionine) [8]. Te methyl group attached to the tertiary sulphur of SAM can be transferred and therefore can cause methylation of other substances. Tis methylation is accompanied by energy loss, so this reaction is irreversible. Te demethyation reaction leads to the formation of SAH (S- adenosylhomocysteine) [8]. SAH is a thioether (a sulfur bonded to two alkyl or aryl groups) analogous to methionine. Te SAM-to- SAH ratio defnes the methylation potential of a cell [7]. Hydrolysis of SAH leads to the formation of homocysteine and adenosine [8]. Tis homocysteine can be used in one of two ways: a) In case of methionine defciency, homocysteine can be re-methylated to form methionine [8]. Te enzyme N5, N10- methylenetetrahydrofolate reductase converts homocysteine to methionine [9]. b) In presence of sufcient methionine, homocysteine is instead used to produce cysteine [8]. Cystathionine-β-synthase is an enzyme (with pyridoxine or vitamin B 6 as an essential cofactor) that converts homocysteine to cysteine [8]. Homocysteine is synthesized from the essential amino acid methionine, therefore cysteine is not an essential amino acid as long as sufcient methionine is available [8] (Figure 1). Biochemistry & Analytical Biochemistry B i o c h e m i s t r y & A n a l y t i c a l B i o c h e m i s t r y ISSN: 2161-1009