Why is carbon monoxide more toxic than carbon dioxide?

CO does not trigger the central or peripheral chemoreceptors. O2 levels remain relatively constant in the presence of CO. The body has chemoreceptors for CO2 (in reality H+ that comes from the carbonic anhydrase reaction) and O2. When pCO2 is too high, many [H+] bind the chemoreceptors. When pO2 is too low, these O2 chemoreceptors will sense this. The compensatory response is to increase ventilation rate and depth to exhale as much CO2 as possible. By Dalton's Law, this decrease in blood CO2 back to normal will increase blood O2 back to normal. CO does not induce a change in ventilation rate. The biochemical details of CO are below.

CO binds where O2 would normally bind on hemoglobin. It does so much faster and binds much tighter. This takes up a space for O2. However, generally in the veins --> right chambers --> pulmonary arterioles, hemoglobin is 75% saturated (3 O2 are already bound to the hemoglobin). Hemoglobin normally can bind a maximum of 4 O2. It cannot do this when CO is present. Hemoglobin bound to CO is called carboxyhemoglobin. It also does not take much CO to bind tightly to hemoglobin.

CO mimics O2 to competitively bind the Fe2+ on a heme group of hemoglobin. When it does so, that heme group shifts to a more relaxed state. This causes an allosteric change in the other heme groups that are bound to oxygen to a relaxed state. This increases hemoglobin's affinity for oxygen. New O2 cannot bind as the hemoglobin is saturated with gases, but by hemoglobin having a higher affinity to O2, the heme groups WILL NOT let go of O2 or CO. This is a real problem when hemoglobin gets to the systemic tissues because hemoglobin cannot deliver O2 to the tissues.

CO DOES NOT CAUSE HYPOXEMIA. THE ISSUE IS NOT LACK OF OXYGEN IN THE BLOOD. If you measure paO2, it will be near 95 mmHg because there is still dissolved oxygen dissolved in plasma. You will see SpO2 will be at the most 75 %. This means the hemoglobin is 75% saturated with O2. This happens to also correlate to reduced O2 carrying capacity in this issue. SpO2 itself does not indicate O2 carrying capacity. Because carboxyhemoglobin still has some O2 bound to it but does not have CO2 bound to it, deceased subjects are still flesh pink.

The reason for the poisoning is inhibited delivery of O2 to the tissues. Tissues deprived of oxygen cannot sustain this for long. Eventually, they will infarct. This will soon lead to death within a couple of minutes.