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MTHFR is the rate-limiting enzyme in the methyl cycle, which includes the conversion of homocysteine into methionine. Defects in variants of MTHFR can therefore lead to hyperhomocysteinemia. [9] There are two common variants of MTHFR deficiency. In the more significant of the two, the individual is homozygous for the 677T polymorphism.
Elevated homocysteine is an independent risk factor for cardiovascular disease and inversely correlated to consumed vitamin B12/B6 and folate levels. [37] Homocysteine methylation to methionine is catalyzed by MTR, resulting in appropriate intracellular levels of methionine and tetrahydrofolate, alongside non-toxic homocysteine levels.
Methylenetetrahydrofolate reductase (MTHFR) is the rate-limiting enzyme in the methyl cycle, and it is encoded by the MTHFR gene. [5] Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine.
A hypomethylating agent (or demethylating agent [1]) is a drug that inhibits DNA methylation: the modification of DNA nucleotides by addition of a methyl group.Because DNA methylation affects cellular function through successive generations of cells without changing the underlying DNA sequence, treatment with a hypomethylating agent is considered a type of epigenetic therapy.
Homocystinuria (HCU) [2] is an inherited disorder of the metabolism of the amino acid methionine due to a deficiency of cystathionine beta synthase or methionine synthase. [3] It is an inherited autosomal recessive trait, which means a child needs to inherit a copy of the defective gene from both parents to be affected.
Measurement of TPMT activity is encouraged prior to commencing the treatment of patients with thiopurine drugs such as azathioprine, 6-mercaptopurine and 6-thioguanine. Patients with low activity (10% prevalence) or especially absent activity (prevalence 0.3%) are at a heightened risk of drug-induced bone marrow toxicity due to accumulation of ...
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