How interventions of coenzyme Q10 and vitamins B, C and K can be used to control levels of phosphatidic acid, a lipid messenger that prevents programmed cell death

Professor Shadyro has shown (1) that when tissue oxygen supply is low (hypoxia), free radicals can react with carbohydrates, amino acids and specific lipids in the cell to form signaling molecules (2). Phosphatidic acid (PA) is a signaling lipid that enables cytosolic proteins to be directed to the appropriate membranes and as such has an important role in apoptosis and cell proliferation processes. Higher levels of PA inhibit normal cell death mechanisms. High PA levels can occur when the cell is under oxidative stress. Thus high tissue levels of PA can result in reduced efficacy of chemotherapy or radiotherapy treatment for carcinomas (3).

Professor Shadyro’s group have found that the metabolic pathways for the production of PA under conditions of hypoxia (4) can be down-regulated by the presence of nutrients containing quinones or conjugated carbonyl groups, including coenzyme Q10 and vitamins B, C and K (5,6). They were able to show that vitamin C regulated recombination and fragmentation reactions of hydroxyl-containing biomolecules that had been induced by reactive oxygenated species (ROS).

1. Shadyro OI; “Radiation-induced free radical fragmentation of cell membrane components and the respective model compounds”; in “Free radicals in biology and the environment”: Dordrecht: Kluwer Academic Publications 1997; 27: 317 – 329.
2. Shadyro OI, Yurkova I, Kisel M et al.; “Radiation induced fragmentation of cardiolipin in a model membrane”; Int J Radiol Bio 2004: 80(3): 239-245.
3. Foster DA; “Phosphatidic Acid signaling to mTOR; signals for the survival of human cancer cells”: Biochim Biophys Acta 2009; 1791 (9); 949-955
4. Shadyro OI, Glushonok GK, Glushonok TG et al.; “Quinones as free-radical fragmentation inhibitors in biologically important molecules”; Free Radical Research 2002: 36 (8): 859 – 867.
5. Shadyro OI, Sosnovskaya AA; Edimechiva IP et al.; “Effects of various vitamins and coenzymes Q on reactions involving apha-hydroxyl-containing radicals”; Free Radical Research 2005; 39(7): 713-718.
6. Brinkevich SD & Shadyro OI; “The effect of ascorbic acid on hemolytic processes involving alpha-hydroxyl containing carbon-centered radicals”; Bioorg Med Chem Let 2008; 18 (24):6448-50.