José A. Hernández Cortés. Research Scientist (CEBAS-CSIC)
In the last chapter, we described non-enzymatic antioxidant defense mechanisms (https://antioxidantsgroup.wordpress.com/2013/07/04/antioxidant-defense-mechanisms-i-non-enzymatic-mechanisms/), so now we are going to talk about enzymatic antioxidants.
– As far as it is known, the only enzyme involved in superoxide radicals elimination is superoxide dismutase (SOD). In fact, there are three different isoenzymes depending on the metal present in their active site (Mn-SOD, Fe-SOD or Cu,Zn-SOD). This group of metalloenzymes catalyzes the dismutation of superoxide radicals to H2O2 and O2:
– H2O2 can be directly removed by the action of the enzyme catalase or by the action of ascorbate peroxidase (APX, that uses ascorbate as electron donor), peroxidases (POX, enzymes that are abundant in cell wall and in vacuoles) which remove H2O2 using different phenolic compounds as reducing power; glutathione peroxidase (which removes H2O2 and hydroperoxides employing GSH as reducing power) or peroxiredoxins using different reducing molecules.
Furthermore, this group of enzymes is supported by other enzymes which act regenerating antioxidant molecules employed by enzymes that remove H2O2. In this group highlight enzymes dehydroascorbate reductase (DHAR) and monodehydroascorbate reductase (MDHAR) whose action is to regenerate ascorbate (or vitamin C). Glutathione reductase (GR) regenerates reduced glutathione (GSH) which is employed by DAHR in ascorbate recycling. Glucose-6-phosphate dehydrogenase (G6PDH) produces NADPH which is employed by GR activity in GSH recycling from oxidized (glutathione GSSG).
The enzymes APX, GR, MDHAR and DHAR act in a coordinated way in a cycle called ascorbate-glutathione (ASC-GSH) cycle whose function is to eliminate H2O2 and regenerate the non-enzymatic antioxidants ascorbate and GSH.
Both in our organism and in plants, when the generation of ROS overcomes antioxidant defence mechanism, an oxidative stress occurs at cell level which can lead to cell death. All this is associated with some pathology in human beings as cancer, cardiovascular diseases, Alzheimer, Parkinson, sclerosis, among others.
But as we have already mentioned, (https://antioxidantsgroup.wordpress.com/2013/06/27/reactive-oxygen-species-friends-or-foes/) ROS are not only harmful molecules for cells, they are also used as messengers in signalling cascades in a great variety of cell processes. For example, in plants, ROS act as second messengers in vital processes as vegetative development and defence mechanisms. In animals, platelets, which are involved in injury healing and blood homeostasis, release ROS to recruit more platelets at the injured areas. They also establish a link to the adaptation of immune system through white blood cells recruitment. Immune system also uses the toxic effects of ROS making them the central part of its mechanism to kill pathogens.
Therefore, the function of ROS in metabolism is dual; they are toxic for cells when they accumulate in excess, but at low levels it has been proved that they can function as bio-signalling molecules.