TET
Jmj C
αKG
Fe2+
Vitamin C
Cofactor

αKG
Alpha-ketoglutarate-dependent hydroxylases

https://en.m.wikipedia.org/wiki/Alpha-ketoglutarate-dependent_hydroxylases

The hydroxylation of methyl lysine to hydroxymethyl lysine is a key intermediate step. The final product of this oxidative reaction is the unmethylated lysine and formaldehyde.

Hydroxylases utilizes ferrous iron (Fe(II)) as a cofactor and αKG as a cosubstrate, catalyzing a hydroxylation reaction that converts the methyl-lysine into a hydroxymethyl-lysine intermediate. This unstable intermediate then spontaneously releases formaldehyde, completing the demethylation process and returning the iron to its active Fe(II) state.

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Magnesium, niacin (vitamin B3), vitamin C & Polyphenols support stem cell regeneration by maintaining energy production through ATP, enhancing NAD+ levels, and protecting stem cells from oxidative damage. Their collective effects improve mitochondrial function, DNA repair, and overall stem cell activity.

Formaldehyde reacts with nitrogen-containing compounds like ammonia and urea to neutralize its toxic properties by forming stable, non-toxic substances.

A common method for neutralizing formaldehyde involves reacting it with ammonia. This reaction forms hexamethylenetetramine, a solid, non-toxic product.

Formaldehyde also reacts with urea, another nitrogen-containing compound. This reaction is the basis for producing urea-formaldehyde resins and slow-release nitrogen fertilizers.

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A protocol for using mRNA to delete stem cells involves packaging the mRNA within lipid nanoparticles (LNPs) and functionalizing the LNPs with aldehydes to promote targeted, covalent bonding to cell surfaces. The mRNA payload can be designed to trigger cell death, while the aldehyde group enhances binding to target cells, a process that can be affected by methylation patterns on the mRNA.

Aldehyde surface functionalization: The surface of the LNPs is modified with reactive aldehyde (-CHO) groups. These groups are highly reactive and can form covalent bonds with nucleophilic groups (like amino and thiol groups) on the surface of target cells. This is used to enhance specific and permanent binding of the LNPs to the stem cell surface.

Epigenetic memory and mRNA: The methylation patterns on the chromosomes act as a form of "epigenetic memory," ensuring the cell's specialized identity is maintained through subsequent cell divisions. This dictates which genes are transcribed into mRNA to create the specialized proteins for that cell type. mRNA methylation, particularly m6A methylation, adds another layer of regulation, influencing the stability and translation of these messages and fine-tuning gene expression during stem cell differentiation.

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histone demethylases cofactor

Key Cofactors by Demethylase Type:

JmjC-Domain Demethylases (KDM2-8):

These enzymes use a different set of cofactors than LSDs.

α-Ketoglutarate (α-KG): This is a key cofactor that participates in the oxidative demethylation process. (Vitamin C)

Iron (Fe(II)): Required alongside α-ketoglutarate for the catalytic activity of the JmjC domain enzymes.

Oxygen: Essential for the hydroxylation reaction that removes methyl groups.

Inhibitory Cofactors:

Metal ions (e.g., nickel) and certain organic molecules (e.g., disulfiram) can act as disruptors, binding to the catalytic sites of demethylases like KDM4 and inhibiting their activity.

Disulfiram Sulfur