Question

1

a) Explain the steps by which reactive drug metabolites or reactive oxygen species cause cell damage and death.

b)What is glutathione (GSH) and why is it important in cells?

Answer 1

a) During Biochemical redox reactions, the transfer of electrons between molecules results in the formation of reactive oxygen species and non-oxygen free radicals in the body. This reactive oxygen species take up a hydrogen molecule from membrane phospholipids which are made up of polyunsaturated fatty acid chains producing reactive free radicals. In the second step, oxygen adds on to the site of the free radical formation to produce a peroxide. This process continues as a chain reaction when this fatty acid peroxide takes up another proton from the membrane and another free radical is produced. It ultimately results in membrane peroxidation which leads to fragmentation of the membrane and release of free radicals in the tissues which degrades the structural integrity and permeability of the membrane. This is followed by modification, oxidation, hydrolysis, fragmentation and inactivation of the proteins and other organelles by the reactive oxygen species and free radicals. They act upon the DNA, producing strand breakage, mutations and interfere in the regulatory control of growth differentiation, cell division and cell death.

B) Glutathione plays a vital role as an antioxidant in cell function by protecting it from the activity of free radicals and reactive oxygen species. Glutathione peroxidase detoxifies hydrogen peroxide using glutathione. Glutathione can either donate protons to combat oxidant stress or take up protons and be considered as a storage form of antioxidant. While combatting free radicals, it is inactivated to the oxidised form but can be regenerated by the action of the enzyme glutathione reductase.