Ascorbic acid (AA) and its role Inhibits aggregation:
As an antioxidant, ascorbic acid can inhibit the aggregation of amyloid-beta peptides by binding directly to the monomers and reducing the amount of beta-sheet structures.
Affects aggregation concentration-dependently:
For some amyloids, like those derived from semen protein, the effect of ascorbic acid is concentration dependent.
High levels of AA inhibit fibril formation, while lower levels can sometimes promote it.
Degradation products disrupt fibrils:
The degradation products of ascorbic acid, such as dehydroascorbic acid (DHA), have been shown to have a disruptive effect on mature amyloid fibrils, more so than intact ascorbic acid.
Dehydroascorbic acid (DHA) and its actions
Redox activity:
DHA is the oxidized form of ascorbic acid. Its cycling back to ascorbate involves enzymes like glutaredoxin and other thioredoxin superfamily members.
Forms disulfide bonds:
DHA can facilitate the formation of disulfide bonds within proteins and peptides through S-thiolation (the addition of a thiol group).
Impact on amyloid:
DHA's role in influencing amyloid-related disulfide bonds is complex. While it can cause disulfide bond formation, the degradation products of AA (including DHA) have been shown to be effective inhibitors of aggregation. Its effect likely depends on the specific protein and cellular context.
How DHA and MSM work together
Faster vitamin C uptake:
While standard vitamin C (ascorbic acid) has limited absorption through the skin and cell membranes, DHA is absorbed more readily using glucose transport systems. Once inside the cells, the body rapidly converts DHA back into ascorbic acid, effectively creating an intracellular vitamin C reservoir.
Improved antioxidant capacity:
MSM itself does not act as a direct antioxidant but can boost the body's natural antioxidant systems. It helps the body produce key antioxidants like glutathione, which is involved in reducing DHA back to active vitamin C.
Factors limiting MSM's Electron and hydrogen donor capability
Highly oxidized sulfur center:
The sulfur atom in MSM is at its maximum oxidation state, meaning it is not electron-rich and is unwilling to give up additional electrons. This is in direct contrast to its chemical precursor, dimethyl sulfoxide (DMSO), which is a much more potent antioxidant because its less-oxidized sulfur atom can donate electrons.
Strong electron-withdrawing effect:
The highly oxidized sulfur center pulls electron density away from the surrounding bonds, including the C-H bonds of the methyl groups. This makes it difficult for MSM to act as a source of hydrogen atoms.
L-Ascorbate vs D-Ascorbate
L-ascorbate is a chiral molecule that exists in a specific three-dimensional structure, whereas D-ascorbate is its mirror image, which cannot effectively bind to vitamin C transporters in the body.