HOMOCYCTEINE AND ITS METABOLISM

Аннотация

Many people have never heard of homocycteine, yet elevated levels of this naturally occurring amino acid can actually increase risk of some serious helth conditions. Homocysteine is an amino acid. Amino acids are chemicals in your blood that help create proteins. Vitamin B12, vitamin B6 and vitamin B9 (folate) break down homocysteine to generate other chemicals your body needs. Many people have never heard of homocycteine, yet elevated levels of this naturally occurring amino acid can actually increase risk of some serious helth conditions. Key words:Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of two pathways: remethylation to methionine, which requires folate and vitamin B12 (or betaine in an alternative reaction); and transsulfuration to cystathionine, which requires pyridoxal-5'-phosphate. The two pathways are coordinated by S-adenosylmethionine, which acts as an allosteric inhibitor of the methylenetetrahydrofolate reductase reaction and as an activator of cystathionine beta-synthase. Hyperhomocysteinemia, a condition that recent epidemiological studies have shown to be associated with increased risk of vascular disease, arises from disrupted homocysteine metabolism. Severe hyperhomocysteinemia is due to rare genetic defects resulting in deficiencies in cystathionine beta synthase, methylenetetrahydrofolate reductase, or in enzymes involved in methyl-B12 synthesis and homocysteine methylation. Mild hyperhomocysteinemia seen in fasting conditions is due to mild impairment in the methylation pathway (i.e. folate or B12 deficiencies or methylenetetrahydrofolate reductase thermolability). Post-methionine-load hyperhomocysteinemia may be due to heterozygous cystathionine beta- synthase defect or B6 deficiency. Early studies with nonphysiological high homocysteine levels showed a variety of deleterious effects on endothelial or smooth muscle cells in culture. More recent studies with human beings and animals with mild hyperhomocysteinemia provided encouraging results in the attempt to understand the mechanism that underlies this relationship between mild elevations of plasma homocysteine and vascular disease. The studies with animal models indicated the possibility that the effect of elevated homocysteine 10 MODELS AND METHODS IN MODERN SCIENCE International scientific-online conference is multifactorial, affecting both the vascular wall structure and the blood coagulation system. Recent epidemiological studies have suggested that hyperhomocysteinemia is associated with increased risk of vascular disease. Homocysteine is a sulphur- containing amino acid whose metabolism stands at the intersection of two pathways: remethylation to methionine, which requires folate and vitamin B12 (or betaine in an alternative reaction); and transsulfuration to cystathionine which requires vitamin B6. The two pathways are coordinated by S- adenosylmethionine which acts as an allosteric inhibitor of the methylenetetrahydrofolate reductase (MTHFR) and as an activator of cystathionine beta-synthase (CBS). Hyperhomocysteinemia arises from disrupted homocysteine metabolism. Severe hyperhomocysteinemia is due to rare genetic defects resulting in deficiencies in CBS, MTHFR, or in enzymes involved in methyl cobalamine synthesis and homocysteine methylation. Mild hyperhomocysteinemia seen in fasting condition is due to mild impairment in the methylation pathway (i.e. folate or B12 deficiencies or MTHFR thermolability). Post-methionine-load hyperhomocysteinaemia may be due to heterozygous cystathionine-beta-synthase defect or B6 deficiency. Patients with homocystinuria and severe hyperhomocysteinemia develop arterial thrombotic events, venous thromboembolism, and more seldom premature arteriosclerosis. Experimental evidence suggests that an increased concentration of homocysteine may result in vascular changes through several mechanisms. High levels of homocysteine induce sustained injury of arterial endothelial cells, proliferation of arterial smooth muscle cells and enhance expression/activity of key participants in vascular inflammation, atherogenesis, and vulnerability of the established atherosclerotic plaque. These effects are supposed to be mediated through its oxidation and the concomitant production of reactive oxygen species. Other effects of homocysteine include: impaired generation and decreased bioavailability of endothelium-derived relaxing factor/nitric oxide; interference with many transcription factors and signal transduction; oxidation of low-density lipoproteins; lowering of endothelium-dependent vasodilatation. In fact, the effect of elevated homocysteine appears multifactorial affecting both the vascular wall structure and the blood coagulation system. Reference: 1.Musher DM, Abers MS, Corrales-Medina VF. Acute infection and myocardial infarction. N Engl J Med. (2019) 2.Duan J, Wu Y, Liu C, Yang C, Yang L. Deleterious effects of viral pneumonia on cardiovascular system. Eur Heart J