Overview L-serine is a nonessential amino acid in eukaryotic cells, used for protein synthesis and in producing phosphoglycerides, glycerides, sphingolipids, phosphatidylserine, and methylenetetrahydrofolate. Moreover, L-serine is the precursor of two relevant coagonists of NMDA receptors: glycine (through the enzyme serine hydroxymethyltransferase), which preferentially acts on extrasynaptic receptors and D-serine (through the enzyme serine racemase), dominant at synaptic receptors. (R1) Serine is essential for cysteine and glutathione synthesis: Homocysteine + Serine –> Cystathionine (which later becomes cysteine) Serine –> Glycine + 1-carbon (glycine is used to form GSH) Consequently, Serine is essential for heme synthesis also (R2).

Basics 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an enzyme that regulates cellular energy homeostasis, glucose, fatty acid uptake, and oxidation at low cellular ATP levels. AMPK is a cellular energy sensor that when activated, stimulates catabolic processes that increase ATP synthesis, and concurrently inhibits anabolic processes that consume ATP. Nutritional or environmental stress, such as hypoglycemia, hypoxia, and/or muscle contraction, lead to an increase in the AMP:ATP ratio. (R3)

Highlights Ascorbate is a vitamin cofactor and an enhancer of dietary iron absorption. Ascorbate regulates cellular iron uptake, ferritin expression, and cell iron efflux. Ascorbate is a novel reductant actively involved in (non)transferrin iron uptake. Ascorbate regulates the IRP–IRE and HIFα systems in iron metabolism. Ascorbate is a regulator of mammalian iron metabolism and homeostasis. Ascorbate stimulates iron uptake by an intracellular reductive mechanism We recently demonstrated that Asc regulates iron uptake from Tf in a variety of human cell types.

Magnesium deficiency Manganese deficiency Iron deficiency Copper deficiency Vitamin D deficiency Vitamin A deficiency Autophagy deficiency Together, these evidences uncover the p62-FOXO1/3 axis as the molecular cue that underlies the impairment of antioxidant defense in autophagy deficiency and suggest its potential involvement in aging, substantiating the impact of inadequate autophagy on mitochondria and redox homeostasis. (R1)

Highlights Thiamine deficiency may have significant impact on the ability of the cells to salvage NAM for synthesis of NAD. People taking high doses of Niacin to boost NAD may also benefit from improving thiamine status. People concerned about NAD+ should pay attention to thiamine as well. Hypothesis: Taking high doses of Niacin or NAM may tax the body in subjects with suboptimal thiamine status.

Dosage for treating Iron Deficiency Oral iron supplementation 1 - 2 mg/kg/day is the preventative dose for iron deficiency 3 - 6 mg/kg/day is the recommended dose for treatment of iron deficiency and IDA. Higher doses should be considered in those children with severe anaemia (Hb <80 g/L). Iron supplements should be continued for a minimum of 3 months after anaemia has been corrected to replenish stores. Hb and ferritin should be checked at this time point.

Retinoic acid ATRA = All-trans-retinoic acid. ATRA down-regulates CBS and BHMT Apparently ATRA down-regulates CBS and BHMT enzymes: These results demonstrate that ATRA intensifies ER stress and induces apoptosis in GnT-V-AS/7721 cells by disturbing homocysteine metabolism through the down-regulation of CBS and BHMT, depleting the cellular GSH and, in turn, altering the cellular redox status. (R1) ATRA induces GNMT and MS (MTR) A significant increase (105%) in GNMT activity was observed with doses as low as 5 μmol/kg body weight, whereas maximal induction (231%) of GNMT activity was achieved at 30 μmol/kg body weight.

Alkaline phosphatase ALP has the physiological role of dephosphorylating compounds. The enzyme is found across a multitude of organisms, prokaryotes and eukaryotes alike, with the same general function but in different structural forms suitable to the environment they function in. Wikipedia ER Stress The unfolded protein response (UPR) is a cellular stress response related to the endoplasmic reticulum (ER) stress Wikipedia The UPR is activated in response to an accumulation of unfolded or misfolded proteins in the lumen of the endoplasmic reticulum.

Highlights Under ER stress the CSE enzyme starts metabolising Cysteine instead of Cystathionine to produce H2S. (R1) CBS deficiency also leads to chronic increase in H2S production (R1) Excess of Hydrogen sulfide is implicated in lowered PPI which can be seen in Schizophrenia and Tourette Syndrome. (R2) Increased production of H2S leads to prolonged sulfhydration of Akt protein, which deactivates it, leading to diminished ability of AKT to deactivate GSK3b by phosphorylation (R5)

Melatonin as a pro-oxidant Melatonin is usually regarded as an antioxidant and a protective agent. Here I provide a few pieces of research that show that Melatonin can be also a pro-oxidant depending on the level of oxidative stress. In yeast, melatonin was shown to reduce GSH and increase GSSG at the same time activating some genes related to antioxidant defense system and downregulating other genes: Melatonin alone decreased GSH, increased GSSG, and activated antioxidant defense system genes, which reached maximum levels in the stationary phase.