Free radicals and cellular injury

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Free radicals and cellular injury

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USMLE® Step 1 style questions USMLE

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A 47-year-old man presents to his primary care provider for a follow-up appointment. He was recently diagnosed with hereditary hemochromatosis. The patient is informed that the liver cells of affected individuals are exposed to more free radical injury than those of healthy individuals. Which enzymes play a vital role in protecting cells from free radical injury?  

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Electrons in an atom are present in spaces called orbitals, and each orbital can fit different pairs of electrons.

Now free radicals are molecules with only one electron, or an unpaired electron, in their outer orbital.

Free radicals have a habit of stealing electrons from any molecule they come across to make themselves stable and it’s what causes all the trouble and potentially can cause cellular injury.

Now, a free radical is formed when any molecule gains or loses an electron.

In the body, free radicals can be generated physiologically, which means as a part of normal metabolic processes; or pathologically, which is due to some disease.  

A major physiological source of free radicals is cellular respiration, which is also called oxidative phosphorylation.

Oxidative phosphorylation is the process of making ATP by donating electrons to complexes embedded within the inner mitochondrial membrane.

Together, they form the electron transport chain, which pass electrons from complex to complex, and finally to oxygen, creating a proton gradient that will be used to make ATP.

The final step of this process involves a molecule called cytochrome c oxidase, sometimes known as complex IV, which transfers electrons to oxygen.

Normally, when oxygen gets four electrons, it gets converted into water.

But when oxygen doesn’t get all four electrons, then it will have unpaired electrons in its orbital, giving rise to free radicals.

Since these are formed from oxygen, they’re collectively called reactive oxygen species, or simply ROS.

Okay so if oxygen is given one electron, it becomes superoxide (O2−) If it gets two electrons, it becomes hydrogen peroxide, or H2O2, and then 3 electrons, it’s the hydroxyl radical (OH.).

There are also pathological conditions where free radicals can be generated.

First, they can be produced during inflammation by phagocytes like macrophages and neutrophils.

When a pathogen invades the body, the phagocyte gobbles up the pathogen forming a phagolysosome.

These phagocytes also have an enzyme called NADPH oxidase, which gets activated by the lysosomal enzymes, causing NADPH to undergo oxidation, and lose two of its electrons.

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