CQ10 deficiency results in increased oxidative stress (In mice) CoQ deficiency results in mitochondrial dysfunction associated with increased mitochondrial oxidative stress and a range of pathologies. R1 PEMT deficiency upregulates CQ10 synthesis (In mice) phosphatidylethanolamine N-methyltransferase (PEMT) deficiency was confirmed as a positive regulator of CoQ synthesis, the first identified to date. Mechanistically, PEMT deficiency alters mitochondrial concentrations of one-carbon metabolites, characterized by an increase in the S-adenosylmethionine to S-adenosylhomocysteine (SAM-to-SAH) ratio that reflects mitochondrial methylation capacity, drives CoQ synthesis, and is associated with a decrease in mitochondrial oxidative stress.

Histamine metabolism is a source of ROS “we demonstrate that exogenous histamine is transported into isolated cardiomyocytes and triggers a rise in the levels of reactive oxygen species (ROS). Once again, pargyline pretreatment induced intracellular accumulation of N¹-methylhistamine along with decrease in ROS levels. These findings uncover a receptor-independent mechanism for histamine in cardiomyocytes. our study reveals a novel and important pathophysiological causative link between MAO activation and histamine availability during pathophysiological conditions such as oxidative stress/cardiac injury.

Vitamin C enhances folate cycle A study (R1) observed significant changes in the metabolites of folate cycle and related metabolites after pre-treatment of the cell with ascorbic acid: Increased level of THF 10-fold Increase of 5-MTHF Decreased level of 10-Formyl-THF Increased level of methionine Increase in Thymidine Quote: Compared to untreated cells, treatment of C2C12 cells with AA at 100 µM resulted in enhanced concentrations of folic acid (2.

Folinic acid is 5-formyl-THF (Wikipedia), or 5fTHF in short. It’s converted to 5,10-methenyl-THF by the enzyme MTHFS (see Reactome). This reaction consumes ATP. 5,10-methenyl-THF is next converted to [5,10-methylene-THF] by the enzyme MTHFD1 and this reaction requires NADPH (see Reactome). 5-formyl-THF is considered to be an intracellular storage form of folate. (R2, R3) Toxicity and disorders It seems it’s possible to get to the toxic level of 5-formyl-THF: a genetic disorder - MTHFS deficiency - is presented with significantly elevated level of 5-formyl-THF and neurometabolic disorder with observed microcephaly, short stature, severe global developmental delay, progressive spasticity, epilepsy, and cerebral hypomyelination.

Any supplemental form of cobalamin is reduced to core cobalamin Vitamin B12 is often sold as a supplement in what is referred to as its “active form,” which is typically either adenosylcobalamin or methylcobalamin. However, when these forms are taken orally or topically, they are not truly active. They undergo processing, during which the alkyl group is cleaved off, and a new methyl or adenosyl group is reattached to the cobalamin:

Hypothesis: Possible implication of MTHF level in tics disorder. Anecdotal evidence: People report that taking Glycine sometimes increase tics (I have similar observations). Personal experience with Serine: apparently it reduces tics, but also can lower energy (and that can be a reason for tics reduction). Serine also being reported by two people to cause negative symptoms in the brain (burning headache, irritability, disinhibition). Carnosine was reported to reduce tics and I saw the same effect.

Dietary intake of glycine is important Our own ability to make Glycine from Serine is limited by the rate of folate cycle: the capability to synthesize glycine from serine is constrained by the stoichiometry of the glycine hydroxymethyltransferase reaction, which limits the amount of glycine produced to be no more than equimolar with the amount of C 1 units produced. This constraint predicts a shortage of available glycine if there are no adequate compensating processes.

Role of Chromium Strengthening PI3K and Akt signalling In a nutritional model of insulin resistance in which the mice were fed a high-sucrose diet or a high-fat diet, chromium treatment reconciled the blunted Akt phosphorylation and the attenuated PI3-kinase activity, consistent with the studies by Cefalu and coworkers. To understand whether this was a direct effect of chromium on insulin signaling, cultured adipocytes were rendered insulin resistant by chronic treatment with insulin and glucose (hyperinsulinemic, hyperglycemic conditions) resulted in a blunting of insulin-stimulated Akt phosphorylation and cellular glucose uptake.

GSH presents mainly inside the cells While GSH can be found in plasma in low concentration, most of GSH is located inside the cells (including Red Blood Cells): Intracellular glutathione concentrations range between 0.5 and 10 mM whereas extracellular glutathione concentrations are significantly lower, with estimated values in the micromolar range. (R1) Cells must make own Glutathione Extracellular supply of GSH is limited by low concentration and by mandatory degradation of GSH on the cell’s membrane TBD