Copper and Ascorbate

There are those that tell you that mixing copper sulfate with ascorbate/vitamin C is the same as CopperOne Niacin. They are both a beautiful orange/red color, are they not? The are not the same! They are two perfectly and required nutrients that do not belong together. Just like….

Mr Fork and Mr Oulet can’t be friends because when you get the two together electrons go where they are not supposed to go. This is the same reason why Mr Copper and Mr Ascorbate cannot be friends. Getting the two together and a source of electrons can result in those electrons going where they shouldn’t.

These are the sources of the animation

1. Mastrangelo D, Massai L. Vitamin C against Cancer. , Chapter 4 in VITAMIN C Edited by Amal H. Hamza Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia This book chapter was used for equations 1-4.
2. Letelier ME, Sánchez-Jofré S, Peredo-Silva L, Cortés-Troncoso J, Aracena-Parks P. Mechanisms underlying iron and copper ions toxicity in biological systems: Pro-oxidant activity and protein-binding effects. Chem Biol Interact. 2010 Oct 6;188(1):220-7. Free article This article spells out how how ascorbate and Fe³⁺ or Cu²⁺ can lead to oxidative stress. Cu²⁺ appears to be worse than Fe3+ in many ways.
3. Belmonte M, Elhiti M, Waldner B, Stasolla C. Depletion of cellular brassinolide decreases embryo production and disrupts the architecture of the apical meristems in Brassica napus microspore-derived embryos. J Exp Bot. 2010 Jun;61(10):2779-94. PMC free article This article was used to fine tune the relationship between ascorbate free radicals and the anti-oxidant small molecule glutathione, GSH

Vitamin C and Fenton reaction [1]

Note that Cu²⁺ can be substituted for Fe³⁺ [2] Radicals, unpaired electrons, in these equation are denoted by superscript”^●“

1. Fe³⁺ + AscH₂ → Fe²⁺ + Asc^●- → + 2H⁺
2. Fe²⁺ + O₂ → Fe³⁺ + O₂^●-
3. 2O₂^●- + 2H⁺→ H₂O₂ +O₂
4. H₂O₂ + Fe²⁺ → Fe³⁺ + OH^– + OH^●-

The Letelier study started with the observation that copper ions can irreversibly and non-specifically bind to thiol groups in proteins. They noted that this non-specific binding property was not as fully addressed for iron ions.

• Cu²⁺/ascorbate elicited more oxygen consumption than Fe³⁺/ascorbate under protein free conditions. [2] see equation #2
• In the presence of cytosolic and microsomal protein, Cu²⁺/ascorbate increased microsomal lipid peroxidation and decreased cytosolic and microsomal content of thiol groups more efficiently than Fe³⁺/ascorbate. [2]
• Finally, Fe³⁺/ascorbate and Cu²⁺/ascorbate inhibited in different ways cytosolic and microsomal glutathione S-transferase (GST) activities, which have subtle differences in sensitivity to oxidants.
• In the absence of ascorbate, only Cu²⁺ decreased the content of cytosolic and microsomal thiol groups and inhibited cytosolic and microsomal GST activities.

The reaction

This reaction was pieced together from references [2] and [3]

1. Asc^●- → dehydro Asc +e^–
2. dehydro Asc + 2GSH → Asc + GSSG

Now that the Ascorbate has been regenerated it is free to start the reactive oxygen species regeneration again with more Cu²⁺.

So why can’t Copper and Vitamin C be “friends”?

Because when the two get together, electrons go where they shouldn’t be.