Question

1. How can hemoglobin deliver oxygen to myoglobin in muscle tissue cells? (use oxygen binding curve, T-state and R-state, sigmoidal, cooperativity, Bohr effect, carbon dioxide, and 2,3-BPG)

Answer 1

Oxygen is taken up by body through respiration in lungs, once oxygen entered in blood from lungs by crossing the alveolar membrane and capillary endothelium. It bind with hemoglobin (Hb) and then are transported to rest of the body.

Hb have four heme group and a central iron ion (Fe2+) which react with four oxygen to form oxyhaemoglobin HbO2. Hb is made of four protein subunit 2 $\alpha \beta$ . When no oxygen is bound, the haemoglobin is said to be in the Tense State (T-state), with a low affinity for oxygen. At low pO2 values, only one subunit will bind an O2 molecule. When it does so, the shape of that subunit changes, causing an alteration in the quaternary structure of the whole Hb molecule. That structural changes makes it easier for the other subunits to bind to a molecule of O2 that is the affinity of Hb for oxygen increase and it convert into Relaxed state (R- state). Therefore, a smaller increase in pO2 is necessary to get most of the Hb molecule to bind two oxyegen molecules, that is to become 50% saturated, thanwas necessary to get them to bind one oxygen molecule, to become 25% saturated. This influence of the bi ding of oxygen by one subunit on the oxygen affinity of the other subunits is called positive cooperaivity.

Below is sigmoidal hemoglobin -O2 binding curve, reflecting interactions between the four subunits of the hemoglobin.

100 95.8 Percent satura 26.8 40 80 120 Oxygen partial pressure (pO,, mmHg)

The below graph shows the R and T state of Hb. This clearly shows that when the affinity of Hb for oxygen increases the curve shift towards left and when affinity decreases the curve snhift towards right.

| R-state curve (high affinity) Saturation 02 Percent To state curve (low affinity poz

The percentage of oxygen bound to haemoglobin is related to the partial pressure of oxygen (pO2) at a given site, when tissue (eg. Muscle cells) starved of oxygen its local pO2 falls below 40mm Hg, result in the release of lots of oxygen to the tissue. Thus the positive cooperativity of oxygen binding by Hb is very effective in making oxygen available to the tissues precisely when and where it is needed most.

Few factors affect the oxygen affinity:

pH - The concentration of hydrogen ions can alter the affinity of haemoglobin to oxygen. This is because haemoglobin in the T-state has a higher affinity for hydrogen ions than it does for oxygen. As pH goes down (so [H+] goes up), Hb enters the T state and its affinity for oxygen goes down. Therefore, more oxygen is needed to achieve maximum percentage saturation. This is known as the Bohr effect. It allows oxygen to dissociate at tissues with a lower pH: a good indicator of rate of cellular respiration. The lower the pH, the more the dissociation curve shifts to right.

2,3-diphosphoglycerate (2,3-DPG) – 2,3-DPG, sometimes referred to as 2,3-BPG, is a chemical found in red blood cells. It is a product from the glucose metabolic pathway. 2,3-DPG decreases the affinity of haemoglobin for oxygen. Levels of 2,3-DPG will increase while at high altitudes to adjust to the relatively low atmospheric oxygen; affinity reduces so more oxygen is released at tissues. The higher the [2,3-DPG], the more the dissociation curve shifts to right.

Carbon dioxide - increase in CO2. ​​​​​concentration also decreases the affinity of Hb for oxygen so more oxygen is released at tissues shifting curve to right.