Oxygen Sensing Machinery : New Discovery of Nobel Laureates

How cells adapt to changes in levels of oxygen ?

A) Mechanism :

HRE Hypoxia Response Element

● This mechanism is an adaptive process.

1) Oxygen is important for all animals because oxygen converts food to energy.

2) When the body has lack of oxygen due to exercise and high altitude ( low oxygen pressure), the body automatically increases the RBC's count for more oxygen binding.

3) Body can sense oxygen level by the two methods :

By the Brain :

Brain can sense oxygen level by the carotid body (located in carotid artery)  and gives signal to the muscles for breath at the time of hypoxia. It controls our respiratory rate.

But brain can't give signal to the kidney cell to produce erythropoietin/EPO ( hormone for RBC production ). EPO secreted in the response to cellular hypoxia.

Now a question will be in your mind that how cell sense about lack of oxygen (hypoxia) ?

This question gave us new research which is very useful for human species.

By the cell :

Oxygen sensing mechanism was present in all cell, not only in kidney cell where EPO is normally produced.

● Main Chemicals For Oxygen Sensing :

1) HIF : Hypoxia Inducible Factor :

◆ It's a transcription factor and a protein complex. It binds to the identified DNA segment.

◆ It consist from two subunits :

A) HIF1 Alpha

B) ARNT ( Arylhydrocarbon Receptor Nuclear Translocator )

◆ when oxygen levels are high, cell contain very little HIF. However, when oxygen levels are low, the amount of HIF increses. It shows that HIF is related to regulation of EPO gene.

When HIF attached to EPO gene / HRE (Hypoxia Response Element) then EPO formed.

At normal oxygen levels ubiquitin degrades HIF-1 alpha. This process called proteasome (it is a process in which unneeded proteins degraded by the tagging of ubiquitin)

2) VHL protein : Tumor Suppressor

◆ It is produced by VHL gene. This protein prevents the cancer.

◆ VHL is responsible for degradation of HIF.
VHL binds with HIF by the presence of oxygen.

Under normal oxygen levels, 2-hydroxylated groups (proline residues) are added at two specific positions in HIF. This process called prolyl hydroxylation. This process change the shape of HIF and it allows VHL to recognize and bind to HIF.
This process control by the help of oxygen sensitive enzymes( prolyl hydroxylase ).

So it's clear that oxygen is important for this reaction and without oxygen this reaction is impossible then cell can sense oxygen level.

This machinery explained by three scientist William G. Kaelin Jr., Sir Peter J. Ratcliffe and Gregg L. Semenza.
The 2019 nobel prize in physiology or medicine goes to them for their discoveries of how cells sense and adapt to oxygen availability.

Oxygen Sensing Mechanism

B) Benefits of this discovery :

1) Adaption in metabolism during low oxygen levels. During exercise and high altitude.

Adaption is-
● Generation of new blood vessels
● RBC production increase

2) Blood vessels and placenta formation during fetal development.

3) Increase immune system.

4) Low risk of anemia

5) Low risk of cancer

6) Many pharmaceutical companies are now focused on developing drugs that can activating and blocking this machinery.

Thanks for read this article till the end if you have any query and doubt you can ask me in comment section or dm me on Instagram ( @prakhar4k ) or write in contact form.

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And tell me how am I explain this machinery.