**5. Is AsA the king of antioxidants?**

The reader probably noticed that, when discussing the effects of AsA deficiency, the word 'antioxidant' was never mentioned. If we just follow the direct way of analyzing the phenotype of *gulo* knockout mutants unable to synthesize AsA, the main information we get is that AsA is specifically required by relevant enzymes belonging to the 2-ODD class. This might appear surprising, considering that AsA is mainly known for its antioxidant properties. A quick recap of the main events that determined the popularity of antioxidants in general, and of AsA in particular, is given below.

The use of the word 'antioxidant' changed over time [43]. It was originally used to indicate antioxygenic substances and inhibitors of enzymes catalyzing oxidative reactions [44], then progressively assumed the current meaning of molecules able to scavenge reactive oxygen species (ROS) [45]. In the current usage, ROS include the molecules resulting from univalent dioxygen reduction (also named reactive oxygen intermediates: hydrogen peroxide, superoxide anion, hydroxyl radical) [46] plus singlet oxygen and ozone, but also organic hydroperoxides and other oxidizing molecules are sometimes considered part of the ROS family [47]. Due to their high reactivity as electron acceptors, ROS can potentially damage several cell components (lipids, proteins, nucleic acids) [48]. ROS quenching occurs when a suitable reducing agent donates its electrons [43]. The best-known physiological antioxidants, i.e. reducing agents able to react with ROS, are AsA, glutathione (GSH) and tocopherols. In addition, plant secondary metabolism produces a number of molecules with reducing properties and putative antioxidant function. Beside the antioxidant molecules mentioned above, aerobic organisms developed several antioxidant enzymes: superoxide dismutases (SOD), catalases (CAT), glutathione peroxidases [49] peroxiredoxins [50] and, in plants only, also AsA peroxidases [51].

It is not surprising that the discovery of this potentially powerful army of anti-ROS weapons induced us to think that ROS must be kept under control [52]. Unfortunately, the popularized and oversimplified version of the complex ROS/ antioxidant interactions has led to the wrong conclusion that ROS are always dangerous and must therefore be entirely scavenged by antioxidants. This shallow, pervasive concept deeply influenced the general public, and unfortunately also some researchers who lost contact with updated scientific literature.
