Abstract
Epigenetic control by methylation is directly dependent on SAM/methionine. Free methionine aside from being used for protein synthesis is activated to universal methyl group donor SAM and the methyl group from it can be transferred mainly onto DNA, histones, mRNA and noncoding (Nc) RNA, in the nucleus and onto various cytosolic recipients by specific methyltransferases. The product S-adenosylhomocysteine (SAH) from methyltransferase reaction is cleaved into free homocysteine and adenosine. Homocysteine has two fates, one to enter methionine resynthesis which requires methionine synthase (MetS), the coenzymes N5-methyltetrahydrofolate (vitamin B9) and methylcobalamin (vitamin B12). The second option of homocysteine is to enter cysteine synthesis pathway which requires cystathionine -synthase (CBS), serine, vitamin B6 (pyridoxal phosphate) and cystathionine γ-lyase (CGL). I predict serine and vitamin B6 are the critical diverting factors in a fully developed organism where the methylation is minimal and all other factors such as MetS, B9, B12, ATP, Methionine adenosyltransferase (MAT), are more relevant during normal development or in abnormal deregulated cancer cell metabolism. In a developed organism the demethylation pathway would play a critical role during tissue regeneration and must involve hydroxylation (CH2OH), oxidation (CHO) and decarboxylation (COOH) and the corresponding hydroxylase, oxidase and decarboxylase. The hydroxylation is predicted to involve vitamin C (ascorbate) and decarboxylation would involve (vitamin B6). The control of methylation and equally the demethylation is extremely crucial for epigenetic control mechanisms (gene suppression/expression) and any dysregulation would cause abnormal tissues/cancer.
Highlights
The element sulfur with an atomic number of 16 and a mass of ~32.07 had been incorporated in various organisms during the course of evolution and it occurs in different redox forms
Sulfate anion is converted into universal sulfonate donor 3’phosphosdenosine 5’phosphosulfate (PAPS) in two steps catalyzed by ATP sulfurylase and APS kinase activities of PAPS synthase (PAPSS) [2]
Methionine is activated to s-adenosylmethionine (SAM) using ATP as an adenosyl donor by methionine adenosyltransferase (EC 2.5.1.6)
Summary
The element sulfur with an atomic number of 16 and a mass of ~32.07 had been incorporated in various organisms during the course of evolution and it occurs in different redox forms. The reduction of sulfate to sulfide doesn’t happen in humans (mammals), instead humans obtain the most reduced sulfide in the form of sulfur amino acid cysteine [5]. A reduced functional group of cysteine that participates in cells redox reactions functioning in the form of glutathione [6] or thioredoxin protein [7]. The role of SAM in histone, DNA and mRNA methylation is extremely crucial in epigenetic regulations of genome/gene expressions [13].
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