Question

Briefly explain the primary mechanism by which ROS damages biological membranes (lipid peroxidation).

Answer 1

Solution

ROS (Reactive Oxygen Species) are the oxygen containing free radicals or compounds that are extremely reactive and capable of independent existence. They contain one or more unpaired electrons and thus have great affinity for electrons from other sources. Some of the commonly occurring ROS molecules are H2O2, singlet oxygen (1O2), superoxide molecule (O2.-), hydroxyl radical (.OH).

Biological membranes are made up of phospholipids. The phosphate moeity faces out of the membrane and being hydrophilic interact with the external aqueous medium. The lipid moeity is hydrophobic and faces inward to stays protected from the external hydrophilic environment. The hydrophobic lipid tails can ontain saturated or poly-unsaturated fatty acid chains. The unsaturated (containing pi-bonds) chains are more prone to ROS attack.

Lipid peroxidation is an autopropagating process that can self sustain and cause extensive damages to tissues by causing cellular death. Lipid peroxidation process can be broadly classified into 3 mechanistic steps:

1. Initiation: This step involves free radical attack by the hydroxyl radical to one of the H-atom of the methyl group ( bridge) between two unsaturated C atoms. This leads to the formation of a lipid radical and a water molecule.

2. Propagation : This step utilizes the H-atom of methyl bridge of another polyunsaturated fatty acid (PUFA).

3. Termination