Leucovorin
Methotrexate
Folate and ascorbate (vitamin C) have a synergistic relationship because ascorbate protects and increases the bioavailability of folate in the body. As an antioxidant, vitamin C prevents the oxidation of unstable, reduced forms of folate.
Leucovorin is a "rescue" medication used to counteract the toxic effects of the chemotherapy drug methotrexate, particularly when high doses are administered. Methotrexate works by interfering with the body's use of folic acid, but leucovorin provides a readily usable form of folate to protect healthy cells from damage.
To stabilize L-ascorbic acid, use a combination of antioxidants like Vitamin E and ferulic acid for maximum effectiveness. Also, control the pH level, keeping it below 3.5 to enhance stability and skin absorption. Another method involves creating derivatives such as magnesium ascorbyl phosphate or ascorbyl palmitate, or using encapsulation to protect the L-ascorbic acid from degradation.
Intermolecular bonding: A 2014 study found that DMSO forms molecular complexes with L-AA through intermolecular hydrogen bonds. This reduces L-AA's oxidation ability and moves its anodic peak potential, confirming the stabilizing effect of DMSO.
Ascorbic acid (Vitamin C) and erythorbic acid are antioxidants that inhibit nitrosamine formation by scavenging nitrites. They work by reacting with nitrites, preventing them from participating in the chemical reaction with amines that creates carcinogenic nitrosamines.
Erythorbic acid is a stereoisomer of ascorbic acid (Vitamin C), with a different arrangement of its hydrogen and hydroxyl groups on the fifth carbon atom.
At high concentrations, erythorbic acid can act as a cytotoxic agent in tumor cells.
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To induce Gulonolactone Oxidase (GULO), you must provide the necessary cellular machinery, such as introducing the GULO gene
For species that synthesize GULO, its expression is linked to glycogen metabolism; therefore, stimulating glycogen breakdown or providing substrate, like L-gulonolactone, increases GULO activity and subsequent ascorbate production.
For cells and organisms that naturally express GULO:
Provide the substrate:
Adding L-gulonolactone to cells increases ascorbate production, indicating a functional GULO enzyme.
Stimulate glycogen metabolism:
GULO is expressed in glycogen-storing organs. Therefore, agents that stimulate glycogen breakdown, such as glucagon, dibutyryl cyclic AMP, or phenylephrine, increase GULO activity.
Use a suitable environment:
GULO is active in a specific pH range, with its activity varying depending on the enzyme source.
Specific examples of inducing GULO:
Transgenic Zebrafish:
The GULO gene from a shark was inserted into zebrafish to reactivate the pathway for ascorbate synthesis.
Cell Cultures:
Adding gulonolactone to human hepatocellular cells and GULO clone cells promotes ascorbate biosynthesis.
Animal Models:
Glucagon, dibutyryl cyclic AMP, and other stimulants that bypass glycogenolysis and increase UDP-glucose levels also stimulate ascorbate synthesis, indicating increased GULO activity.
The pseudogene GULOP is the non-functional remnant of the GULO gene, the resulting inability to produce ascorbate, known as hypoascorbemia, may be linked to certain aspects of tumorigenesis.
https://en.m.wikipedia.org/wiki/L-gulonolactone_oxidase
The loss of endogenous ascorbate production, apo(a) and Lp(a) were greatly favored by evolution, acting as ascorbate surrogate, since the frequency of occurrence of elevated Lp(a) plasma levels in species that had lost the ability to synthesize ascorbate is great. Only primates share regulation of CAMP gene expression by vitamin D, which occurred after the loss of GULO gene.