The metabolism and significance of homocysteine in. Hcy is degraded in the body through two metabolic pathways, while a minor. Elevated plasma homocysteine is positively associated with. B vitamins and the aging brain selhub 2010 nutrition. Of these subjects, 7 who were diagnosed with diabetes at baseline were. The two pathways are coordinated by adenosylmethionine, which acts as an allosteric inhibitor of the. Elevated total plasma homocysteine has been established as an independent risk factor for thrombosis and cardiovascular disease. Pdf elevated plasma homocysteine is associated with an increased risk of myocardial infarction, stroke, and venous thromboembolism.
Vitamin b6 metabolism and homocysteine in endstage renal. Vitamins are necessary in the metabolism of homocysteine. Creatine supplementation decreases homocysteine in an. Objective to investigate the potential use of the plasma homocysteine level as a predictor of diabetes in women with a previous history of gestational diabetes mellitus gdm. Homocysteine, hyperhomocysteinemia, homocysteine metabolism, disturbance of homocysteine metabolism, nutritional deficiencies, cardiovascular diseases.
Cardiovascular risk factors in the childhood population may be related to the appearance of cardiovascular disease at adult age. Disturbed homocysteine metabolism is associated with. Although the link between methyl groups and epigenetic control of gene expression is relatively clear from a mechanistic point of view 6, 7, the relationship between aberrant homocysteine metabolism and numerous. Sadenosylmethionine is an allosteric inhibitor of methylenetetrahydrofolate reductase 18, an. It can be metabolised by different pathways, requiring. Impaired homocysteine metabolism and atherothrombotic disease.
Bvitamins, homocysteine metabolism and cvd proceedings. Is it a clinically important cardiovascular risk factor. Bostom a, kronenberg f, jacques p, kuen e, ritz e, konig p, kraatz g, lhotta k, mann j, muller g, neyer u, riegel w, schwenger v, riegler p, selhub j. It is an amino acid produced via demethylation of dietary methionine, which is abundant in animal protein. Homocysteine and neurologic disease neurology jama. There is a tight regulation of homocysteine metabolism based upon the very different affinities of methionine synthase and cystathionine synthase for homocysteine. Methyl group and homocysteine metabolism have emerged as a metabolic process that has profound effects on health and disease, particularly when it is disrupted 15. Methionine is then activated by atp to produce sam, which donates a. We have assessed the activity of the 3 prime enzymes of homocysteine. Elevated homocysteine promotes atherosclerosis through increased oxidant stress, impaired endothelial function, and induction of thrombosis.
The homocysteine hypothesis of depression american. The hypothesis that homocysteine causes vascular disease was proposed over 30. Homocysteine levels are relatively stable through the first 4 decades of life and then rise sharply, particularly after age 70. Homocysteine is a sulfurcontaining amino acid derived from the metabolism of methionine, an essential amino acid, and is metabolized by one of the two pathways. The levels of hcy can be increased by defective metabolism of met, resulting. Homocysteine and hyperhomocysteinaemia bentham science. Roles of homocysteine in cell metabolism medina 2001.
It is biosynthesized from methionine by the removal of its terminal c. Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of two pathways. Homocysteine thcy is a risk factor for atherosclerosis in patients with endstage renal disease and chronic renal insufficiency cri. The hypothesis that homocysteine is atherogenic was proposed more than 30 years ago by kilmer mccully, 1 who observed vascular lesions in children with inherited disorders of methionine metabolism. The clinical significance of elevated plasma homocysteine. There is evidence that circulating homocysteine concentrations may be a. The association is independent of other factors, it is fairly consistent across many studies, it is strong and doserelated, and it is. Here, we established gene expression profiles of 8 hcy metabolic and 12 methylation enzymes in 20 human and 19 mouse tissues through bioinformatic analysis using expression sequence tag clone counts in tissue. Drugs affecting homocysteine metabolism springerlink. Homocysteine metabolism homocysteine metabolism selhub, j.
Although about half of americans have levels of cholesterol that place them at high risk of coronary artery disease, hypercholesterolemia is now considered only one risk factor within a complex amalgam of factors. Department of agriculture human nutrition research center on aging at tufts university, boston, massachusetts, usa. Homocysteine is a sulfurcontaining, nonprotein, toxic amino acid found in the pathway for the interconversion of two amino acids. To investigate the effect of ldopa administration and bvitamin status on plasma homocysteine concentrations in humans with pd.
The transsulfuration of homocysteine to cysteine is catalyzed by cystathioninebetasynthase, a process that requires pyridoxal phosphate vitamin b6 as. Effect of folic acid on methionine and homocysteine. Homocysteine hcy is a sulfur containing amino acid formed during the metabolism of methionine met to cysteine cys. Homocysteine an emerging cardiovascular risk factor article by pamlab. Homocysteine hcy metabolism involves multiple enzymes. Research design and methods at 6 weeks postpartum, baseline examination was performed in 177 gadnegative subjects. Creatine supplementation decreases homocysteine in an animal model of uremia. Role of homocysteine in the development of cardiovascular. Ageassociated changes in the metabolism of vitamin b12 and folic acid. Impaired homocysteine metabolism in earlyonset cerebral and peripheral occlusive arterial disease. Folic acid lowers, but does not normalize, the plasma homocysteine level in patients with esrd, but its effect on whole body metabolism of homocysteine is unknown. A strong relationship between plasma homocysteine levels and mortality has been reported in patients with angiographically confirmed coronary artery disease. Homocysteine and alzheimers disease the lancet neurology.
Homocysteine an emerging cardiovascular risk factor. Since mccullys pioneering observations in 1969, a large number of epidemiological studies have confirmed that an elevation of total plasma homocysteine thcy is prevalent in patients with stroke. Selhub j, miller jw 1992 the pathogenesis of homocysteine. Methyl transfer from methylthf to homocysteine, which is catalysed by vitaminb12dependent methionine synthase, produces methionine and tetrahydrofolate thf. Impaired homocysteine metabolism and atherothrombotic. Determinants of homocysteine metabolism impairment. J selhub, 711 washington street, boston, ma 02111, usa.
Proteinuria as a predictor of total plasma homocysteine. In spain there is little information on the prevalence of hyperhomocysteinaemia and associated vitamin factors among the general population, and less still among children. Folate and vitamin b 12 status in relation to anemia, macrocytosis, and cognitive impairment among older americans in the age of folic acid fortification. Vitamin b6 deficiency may result in high thcy levels, especially after a methionine load pml. For more than 20 years, moderately raised concentrations of total homocysteine thcy have been associated with an increased risk of atherothrombotic vascular events but only recently has evidence mounted to suggest that the association may be causal. Regulation of homocysteine metabolism and methylation in. The prevalence of cognitive impairment increases with age and represents a major public health concern in aging populations. Friedman an, bostom ag, selhub j, levey as, rosenberg ih. A controlled trial of homocysteine lowering and cognitive. Many publications link high homocysteine levels to cardiovascular disease. Homocysteine and vascular disease european heart journal.
Figure two cycles in the metabolism of homocysteine. Methods we studied the effect of 3 weeks of oral treatment with 5 mg folic acid per day on homocysteine metabolism in six chronic hemodialysis patients and six healthy controls. Public health significance of elevated homocysteine. Selhub jean mayer usda human nutrition research center on aging, tufts university, boston, massachusetts 02111. Effects of folic acid and vitamin b12 supplements on. Homocysteine hcy is a thiol group containing the amino acid, which naturally occurs in all humans. Therefore, we evaluated vitamin b6 metabolism and thcy fasting and pml levels in patients with cri and those on hemodialysis hd therapy before and during high. It is a homologue of the amino acid cysteine, differing by an additional methylene bridge ch 2. Genetics of homocysteine metabolism and associated disorders. Methionine is converted to sadenosylmethionine, which is demethylated to sadenosylhomocysteine by methyltransferases.
A number of b vitamins in particular folic acid, pyridoxal, and vitamin b12 are involved in homocysteine metabolism so that deficiencies of these vitamins are among the most common causes of. Proteinuria and plasma total homocysteine levels in chronic renal disease patients with a normal range serum creatinine. This effect of ldopa on plasma homocysteine is accentuated under conditions of impaired homocysteine metabolism such as folate deficiency. Effect of ldopa on plasma homocysteine in pd patients. Prospective studies have shown that elevated plasma homocysteine concentrations increase risk of cardiovascular disease by twofold and risk of cerebrovascular disease to a lesser degree. Homocysteine is metabolized by one of two pathways. Homocysteine, a sulfhydrylcontaining amino acid, is an intermediate product in the normal biosynthesis of the amino acids methionine and cysteine. In remethylation, homocysteine forms methionine by the addition of a methyl group from 5methyltetrahydrofolate or betaine. Homocysteine can be recycled into methionine or converted into cysteine with the aid of certain bvitamins. Public health signi cance of elevated homocysteine abstract homocysteine is a sulfur amino acid whose metabolism stands at the intersection of two pathways.