Hemoglobin, one of the most widely studied and well-known proteins, is of critical importance to our circulatory system. If you’ve heard of hemoglobin before, you might know that it is responsible for delivering oxygen, the red color of blood, etc. But it turns out that it’s even more functional than that — hemoglobin proteins also have built-in oxygen sensors that send a chemical alert to your body when the hemoglobin is out of oxygen.

Deoxygenated hemoglobin molecule — PDB code 4HHB

This chemical alert comes in the form of nitric oxide (NO), a molecule that the body uses as a chemical signal in processes throughout the body. One of the processes our body controls with nitric oxide is the dilation of blood vessels.

The amino acid cysteine — note the -SH functional group on the left

One of the molecular pathways of nitric oxide signalling involves the amino acid cysteine. Cysteine is known to bind reversibly with nitric oxide molecules (NO) to form S-nitrosocysteine, in a process called S-nitrosylation — hence the name of this hemoglobin molecule.

S-nitrosocysteine on the beta subunit — PDB code: 1BUW

Most of the hemoglobin in the human body is Hemoglobin A, made of two alpha subunits and two beta subunits. These beta subunits contain a specially positioned cysteine that binds well with nitric oxide when hemoglobin is in its oxygenated conformation, but does not bind so well to the deoxygenated form. Hemoglobin, like many proteins, will change in shape based on its chemical environment. So when hemoglobin has oxygen bound to its heme centers, it has a different shape from when it has exhausted its oxygen molecules.

Hemoglobin’s alpha chains (red, gray) and beta chains (blue, green).

So, as blood flows through your tissues to deliver oxygen, hemoglobin lets go of its oxygen molecules and morphs into its deoxygenated form, which then causes the release of its nitric oxide molecules. These nitric oxide molecules are absorbed by the surrounding blood vessels, causing them to dilate. This increases blood flow to dilated region of the blood vessel, enabling other oxygen-rich blood cells to supply the tissues in need.

O2 bound to the heme of hemoglobin

To recap: Hemoglobin has built- in oxygen sensors in the form of NO-binding cysteines that tell your body when a blood cell has depleted its oxygen supply so that tissues in need of oxygen can expand their blood vessels to allow more blood flow, thus increasing oxygen delivery. Dang.

Regarding the name of this molecule:

Scientists and engineers love using fancy, confusing words because they make it easier to communicate key information more efficiently to knowledgeable audiences. Unfortunately for the rest of us, all of this ‘science language’ can make these ideas unreachable, hidden behind a wall of jumbled letters. A crucial part of our mission at Nanome is to make science more intuitive and accessible, so we try to write these articles making minimal assumptions about our readers’ preexisting knowledge. Our goal is to write articles in a way that is engaging to knowledgeable audiences while remaining accessible to those with less background — if we are missing on either side, please leave a comment and let the author know. We are striving to open up the world of the nanoscopic to everyone from pharmaceutical chemists to English teachers.

Links!

http://www.jbc.org/content/288/37/26473.full

https://pdb101.rcsb.org/motm/233