Cellular demand for antioxidants?

Question

Antioxidants such as ascorbate and glutathione serve to inactivate radicals and counteract spontaneous oxidation reactions, such as unwanted disulfide bonds in proteins. These systems are cycles, where a "spent" antioxidant (say, oxidized glutathione) is convert back to its reduced form by another reducing agent, usally NADPH.My question is, how much NADPH (or reducing equivalents) does a cell devote to this antioxidant defense? What is the flux, in molar amounts per unit time, through these systems? Does it represent a large portion of the energy metabolism of cells?I am guessing that the flux is quite large, but I have never seen any data on this. Most likely it varies a lot between cell types, but I would be happy to see *any* numbers. I think this is important for understanding antioxidant chemistry in cells, yet it is rarely discussed in the literature.

Answer 1

This is a fascinating question.

I dug into the academic literature regarding quantitative experiments measuring metabolic flux of NAPDH. There is a Nature article, published in 2014, titled "Quantitative flux analysis reveals folate-dependent NADPH production," which examines the cystolic flux of NADPH by using a deuterium tracer to analyze the incorporation of this deuterium tracer into NADPH. Per this article, they quoted the flux to be about 10nmol per uL of cells per hour. This represents 5-20% of the total glucose uptake rate.

Hope this helps.

Daniel