Biochemistry of methylation
Methyl Group Donors
-S-adenosylmethionine (SAM)
LOW: MAT SNP or lack of cofactors
(ATP, Mg, K).
HIGH: SAM supplementation.
LOW: Decreased protein intake,
protein malabsorption/maldigestion
HIGH: MAT SNP or lack of
cofactors (ATP, Mg, K); alcohol, oxidative stress affecting MAT.
LOW: Low intake;
malabsorption/maldigestion.
HIGH: Dietary intake (eggs);
upregulation of betaine/choline backup pathway
LOW: Decreased dietary choline
intake.
HIGH: High dietary betaine intake
(beets, spinach, pears, apples) or choline intake.
LOW: Decreased dietary intake;
malabsorption/maldigestion.
HIGH: High dietary intake (nuts,
eggs, peanuts, almonds, sweet potatoes, pumpkin seeds, spirulina, and
free-range meats).
Methyl Group Metabolites
LOW: Lack of SAM/methyl donors.
HIGH: AHCY SNP or need for
vitamin B3 as a cofactor; elevated homocysteine.
LOW: May be a sign of excessive methylation, CBS C699T SNP in the presence of oxidative stress or inflammation; AHCY SNP (lack of vitamin B3).
HIGH: Vitamin B6 or iron
deficiency (cofactors of the CBS enzyme); enzyme deficiency in MTR/MTRR/BHMT;
folate deficiency with low choline intake; alcohol; tobacco.
LOW: Decreased choline/betaine
intake; malabsorption/maldigestion; zinc deficiency (BHMT cofactor).
HIGH: DMG or betaine
supplementation; BHMT SNP.
HIGH: Betaine, DMG
supplementation; dietary intake (eggs, legumes, nuts, and meats) and
environmental sources (toothpaste, creams, and soaps); folate deficiency
(increases use of the betaine reserve pathway and is required as a cofactor in
the mitochondrial enzyme sarcosine dehydrogenase used to convert sarcosine to
glycine); SAMe supplementation; consider overmethylation.
LOW: Decreased intake,
potentially overmethylation, excessive methyl supplementation.
HIGH: Dietary intake (meat, fish,
legumes, and gelatins) or supplementation; GNMT SNP or cofactor deficiency;
SHMT SNP or cofactor deficiency (vitamin B6, iron).
Transsulfuration
LOW: Requirement for vitamin B6
cofactor for CBS enzyme.
HIGH: CBS SNP; elevated SAM that
directly regulates CBS enzyme; DMG, betaine supplementation; high oxidative
stress or inflammation; requirement for vitamin B6 cofactor for CTH enzyme.
LOW: Requirement for vitamin B6
cofactor for CBS and CTH enzymes.
HIGH: CBS SNP; elevated SAM that
directly regulates CBS enzyme; high oxidative stress or inflammation;
requirement for zinc cofactor for GSS enzyme.
LOW: High oxidative stress; high
requirement for GSH (reduced glutathione); poor food intake,
malabsorption/maldigestion.
HIGH: Dietary intake (energy
drinks, dairy, shellfish, and turkey); CBS SNP in the absence of oxidative
stress or inflammation, or adequate GSH levels.
LOW: Decreased homocysteine,
decreased GSH precursors (cysteine, glycine, glutamate); increased phase II
detoxification conjugation.
HIGH: Dietary intake of precursor
amino acids (cysteine, glycine, glutamate); supplementation; CBS SNP in the
presence of oxidative stress or inflammation; inability to convert oxidized GSH
to reduced GSH (making excess due to inability to reduce it for use).
NOTE: The enzyme glutathione reductase (GR) catalyzes the reduction of oxidized glutathione (GSSG) to reduced glutathione (GSH), which is essential for resisting oxidative stress.
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