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Methionine cycle with BHMT path
The Methionine cycle is a crucial biochemical pathway involved in the metabolism of methionine, an essential amino acid. It plays a pivotal role in various biological processes including methylation reactions, synthesis of important molecules, and the recycling of homocysteine to methionine. Here's a breakdown of the key steps and functions within the Methionine cycle:
- Conversion of Methionine to S-adenosylmethionine (SAM): Methionine, obtained from dietary sources, is converted to S-adenosylmethionine (SAM) through a reaction catalyzed by the enzyme methionine adenosyltransferase. SAM is the principal methyl donor in numerous methylation reactions in the body.
- Conversion of S-adenosylmethionine to SAH (S-adenosylhomocysteine): After donating its methyl group in various methylation reactions, SAM is converted back to S-adenosylhomocysteine (SAH). This reaction is reversible and is catalyzed by various methyltransferase enzymes.
- Conversion of SAH to Homocysteine: SAH undergoes a hydrolysis reaction to produce homocysteine and adenosine. This step is facilitated by the enzyme SAH hydrolase.
- Conversion of Homocysteine to Cysteine using B6 as a cofactor: Homocysteine can be converted to cysteine through a process involving vitamin B6 as a cofactor. This reaction occurs via the transsulfuration pathway, which is crucial for cysteine synthesis.
- Conversion of Cysteine to Glutathione: Cysteine, derived from homocysteine, is utilized in the synthesis of glutathione, a powerful antioxidant that plays a key role in protecting cells from oxidative damage.
- Conversion of Homocysteine to Methionine : Homocysteine can be remethylated back to methionine with the help of vitamins B6, B2 (riboflavin), B12 (cobalamin), and B9 (folate). This remethylation process is essential in maintaining methionine levels and is catalyzed by methionine synthase.
- Cycle of activating folic acid: Methylene tetrahydrofolate reductase (MTHFR) enzyme plays a crucial role in converting inactive folic acid into its active form, which is essential for the remethylation of homocysteine to methionine. Polymorphisms on MTHFR are common, which can lead to stacking of homocysteine and folic acid, and having insufficient amounts of SAM.
- Alternative Conversion of Homocysteine to Methionine: Betaine homocysteine methyltransferase (BHMT) is an alternative pathway that utilizes choline and betaine to convert homocysteine back to methionine, providing an additional route for methionine regeneration.
- Utilization of S-adenosylmethionine (SAM) for various reactions: SAM serves as a methyl donor in reactions involving the methylation of arginine and lysine, and DNA. Additionally, SAM is involved in the synthesis of adrenaline from dopamine and in the synthesis of melatonin.
The Methionine cycle is a complex and tightly regulated pathway crucial for various biological functions, including methylation, antioxidant defense, neurotransmitter synthesis, and overall cellular health.
conceptSAM-e (S-adenosylmethionine, SAMe)
S-Adenosyl-Lmethionine (SAM) is an important molecule in normal cell function and survival. SAM is utilized by three key metabolic pathways: transmethylation; transsulfuration; and polyamine synthesis. In transmethylation reactions, the methyl group of SAM is donated to a large variety of acceptor substrates including DNA, phospholipids and proteins. Thus, interference of these reactions can affect a wide spectrum of processes ranging from gene expression to membrane fluidity. In transsulfuration, the sulfur atom of the SAM is converted via a series of enzymatic steps to cysteine, a precursor of taurine and glutathione, a major cellular anti-oxidant. Polyamines are required for normal cell growth.
Ref:
Lu SC. S-Adenosylmethionine. Int J Biochem Cell Biol. 2000 Apr;32(4):391-5. doi: 10.1016/s1357-2725(99)00139-9. PMID: 10762064.
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