Carboxyhemoglobin

Carboxyhemoglobin (carboxyhaemoglobin BrE) (symbol COHb or HbCO, also known as carbonylhemoglobin) is a stable complex of carbon monoxide and hemoglobin (Hb) that forms in red blood cells upon contact with carbon monoxide. Carboxyhemoglobin is often mistaken for the compound formed by the combination of carbon dioxide (carboxyl) and hemoglobin, which is actually carbaminohemoglobin. Carboxyhemoglobin terminology emerged when carbon monoxide was known by its historic name, "carbonic oxide", and evolved through Germanic and British English etymological influences; the preferred IUPAC nomenclature is carbonylhemoglobin.

The average non-smoker maintains a systemic carboxyhemoglobin level under 3% COHb whereas smokers approach 10% COHb. The biological threshold for carboxyhemoglobin tolerance is 15% COHb, meaning toxicity is consistently observed at levels in excess of this concentration. The FDA has previously set a threshold of 14% COHb in certain clinical trials evaluating the therapeutic potential of carbon monoxide.

The average red blood cell contains 250 million hemoglobin molecules. Hemoglobin contains a globin protein unit with four prosthetic heme groups (hence the name heme -o- globin); each heme is capable of reversibly binding with one gaseous molecule (oxygen, carbon monoxide, cyanide, etc.), therefore a typical red blood cell may carry up to one billion gas molecules. As the binding of carbon monoxide with hemoglobin is reversible, certain models have estimated that 20% of the carbon monoxide carried as carboxyhemoglobin may dissociate in remote tissues.

In biology, carbon monoxide is naturally produced through many enzymatic and non-enzymatic pathways. The most extensively studied pathway is the metabolism of heme by heme oxygenase which occurs throughout the body with significant activity in the spleen to facilitate hemoglobin breakdown during erythrocyte recycling. Therefore heme can both carry carbon monoxide in the case of carboxyhemoglobin, or, undergo enzymatic catabolism to generate carbon monoxide.

Carbon monoxide was characterized as a neurotransmitter in 1993 and has since been subcategorized as a gasotransmitter.

Most endogenously produced carbon monoxide is stored as carboxyhemoglobin. The gas primarily undergoes pulmonary excretion, however trace amounts may be oxidized to carbon dioxide by certain cytochromes, metabolized by resident microbiota, or excreted by transdermal diffusion.

Compared to oxygen, carbon monoxide binds with approximately 240 times greater affinity, however the affinity of carbon monoxide for hemoglobin varies both across species and within a species. In the 1950s, Esther Killick was among the first to recognize a difference in carbon monoxide affinity between adult and foetal blood, and a difference between humans and sheep. In humans, the Hb-Kirklareli mutation has a relative 80,000 times greater affinity for carbon monoxide than oxygen resulting in systemic carboxyhemoglobin reaching a sustained level of 16% COHb. Other human mutations have been described (see Hemoglobin variants). Structural variations and mutations across other hemoproteins likewise affect carbon monoxide's interaction with the heme prosthetic group as exemplified by cytochrome P450 where certain forms of the CYP3A family is relatively less affected by the inhibitory effects of carbon monoxide.

Murinae species have a COHb half-life of 20 minutes compared to 300 minutes for a typical human (see § Toxicokinetics). As a result, the metabolic kinetics, blood saturation point, and tolerance for carbon monoxide exposure vary across species, potentially leading to data inconsistencies pertaining to the toxicology of carbon monoxide poisoning and pharmacology of low-dose therapeutic protocols.