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HOMOCYCTEINE AND ITS METABOLISM
Tojiboyev Tojiboy Alisherovich
Head of the rheumatology department of Ferghana
Medical Institute of Public Health
https://doi.org/10.5281/zenodo.13892931
Annotation
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 div 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
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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.
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