Carbon monoxide is being made inside the human body at this moment. As cells dismantle haem, an iron-containing molecular structure best known for its role in haemoglobin, an enzyme cuts open the ring and releases a molecule made of one carbon atom and one oxygen atom. At that scale and in that setting, the gas is not an intruder. It is part of ordinary metabolism.
The same two-atom molecule becomes poisonous when it enters the lungs from a generator, furnace, fire or engine and reaches the blood faster than the body can remove it. Carbon monoxide binds strongly to haemoglobin, reduces oxygen delivery and also interferes with the way cells use oxygen. Nothing about the molecule itself has changed.
What changes is its concentration, route and location. Inside tissues, tightly limited carbon monoxide produced by haem oxygenase can interact with proteins involved in inflammation and responses to cellular stress. In a contaminated room or vehicle, an uncontrolled external dose can disable the chemistry that keeps the brain and heart alive.
The cell opens a haem ring
Red blood cells circulate for roughly 120 days before macrophages in the spleen, liver and bone marrow dismantle them. Their haemoglobin is separated into reusable components, including the haem groups that held oxygen during the cells’ working lives. Similar haem structures also sit inside enzymes and proteins throughout the body, carrying electrons or helping cells sense gases.
Haem oxygenase performs the decisive cut. The reaction consumes oxygen and reducing power, then produces biliverdin, ferrous iron and carbon monoxide in equal molecular amounts. Biliverdin is subsequently converted into bilirubin, while the iron can be captured and recycled. Space Daily has examined how closely packed haem groups move electrons through proteins; haem oxygenase handles the other end of that chemistry, when the ring itself must be taken apart.
The body uses two main forms of the enzyme. Haem oxygenase-1, or HO-1, is strongly induced by excess haem, inflammation and oxidative stress. Haem oxygenase-2, or HO-2, is expressed more continuously in tissues including the brain. A 2026 review of endogenous carbon monoxide and the stress response describes both enzymes as sources of CO during haem catabolism, while emphasising that their expression and effects differ by tissue.
Some of the resulting CO binds to haem proteins near its source. Some reaches the circulation as carboxyhaemoglobin, and some is eventually carried to the lungs and exhaled. The US Centers for Disease Control and Prevention explicitly notes endogenous haem metabolism when interpreting low carboxyhaemoglobin measurements, particularly in conditions that accelerate red-cell destruction.
There is no tiny reservoir of gas waiting inside a healthy cell. Carbon monoxide diffuses, binds and is cleared. Its biological effects arise from brief molecular encounters with metal-containing proteins, not from the body filling tissues with anything resembling exhaust.
How a poison becomes a signal
Carbon monoxide can bind to iron and other metal centres within proteins, altering how those proteins behave. That gives it access to signalling pathways involved in blood-vessel tone, mitochondrial activity, ion channels and inflammatory gene expression. The effect depends on which protein is present, how much CO reaches it and what condition the cell is already in.
One influential experiment came from Leo Otterbein, Augustine Choi and colleagues in 2000. Working with cultured macrophages and mice exposed to bacterial lipopolysaccharide, the team found that low concentrations of CO suppressed several pro-inflammatory cytokines and increased the anti-inflammatory cytokine interleukin-10. Their Nature Medicine paper traced the effect to a mitogen-activated protein kinase pathway.
That experiment established a mechanism under controlled laboratory conditions. It did not show that breathing combustion fumes benefits people, and it did not turn carbon monoxide into a general anti-inflammatory treatment. The distinction matters because an effect observed in stimulated cells or an animal model may disappear, reverse or become unsafe at a different dose.
Other experiments have found endogenous CO working in less obvious systems. In 2018, Saika Minegishi and colleagues used a selective CO scavenger in mice and observed disruptions in rhythmic clock-gene expression in the liver. The study linked internally produced CO to the mammalian circadian clock, but its mouse experiments did not establish the same intervention as safe or useful in humans.
Biologists group carbon monoxide with nitric oxide and hydrogen sulphide under the term gasotransmitters. All three are small gases produced within living systems, and all three can influence cellular targets while becoming toxic at greater exposure. Their chemistry makes them fast and mobile signals, but also makes dosage unusually difficult to control.
The dose and route change everything
In poisoning, inhaled carbon monoxide crosses from the lungs into the blood and competes with oxygen for haemoglobin. It also shifts the remaining oxygen so that haemoglobin releases it less readily, and it can disturb respiration inside mitochondria. The brain and heart, both demanding continuous oxygen, are especially vulnerable.
No single concentration predicts exactly when a person will collapse. Exposure time, breathing rate, pregnancy, age, anaemia and heart or lung disease all change the risk. The US National Institute for Occupational Safety and Health sets 1,200 parts per million as immediately dangerous to life or health, while its historical human data show why a concentration must always be paired with an exposure duration.
Carboxyhaemoglobin provides evidence of exposure, but it is not a perfect severity gauge. CDC guidance says a level of 2 per cent in a non-smoker or above 9 per cent in a smoker strongly supports poisoning, yet the measurement may fall after a person leaves the contaminated air. A conventional two-wavelength pulse oximeter can also be misleading because it does not accurately distinguish carboxyhaemoglobin from oxygen-carrying haemoglobin.
The first symptoms are often ordinary ones: headache, dizziness, weakness, nausea or confusion. The gas has no colour or smell to announce the source, and several people in the same space may become ill together. The US Environmental Protection Agency advises immediate fresh air and medical attention when exposure is suspected.
Dose-dependent chemistry is not unique to carbon monoxide. Space Daily has described how oxygen was poisonous to much of Earth’s early anaerobic life before later organisms evolved ways to control and exploit it. Carbon monoxide presents the contrast inside one modern body, where an enzyme-generated trace and an inhaled environmental exposure follow profoundly different paths.
Why researchers want to deliver it
The protective effects associated with the HO-1 and CO pathway have made controlled delivery an active research field. Experiments have explored inhaled CO, liquid formulations and carbon monoxide-releasing molecules, usually called CORMs. The goal is not to expose the whole body to a poisonous atmosphere, but to deliver a measured amount to a chosen tissue for a limited time.
CORMs are chemical carriers designed to release CO under particular conditions, such as a change in light, acidity or enzyme activity. Their behaviour is harder to interpret than the name suggests. Researchers must separate the effects of released CO from those of the carrier, its metal components and the chemical fragments left behind, a problem discussed in a 2026 review of controlled CO donors.
Human research has begun, but it remains experimental. A registered early-phase study of HBI-002 examined the safety and pharmacokinetics of an oral CO formulation in healthy volunteers. A separate trial registration in sickle cell disease is testing safety, pharmacokinetics and preliminary efficacy.
A trial registration is not evidence that a treatment works, and no one should attempt to reproduce these exposures outside a controlled medical study. Investigators monitor dose, symptoms and carboxyhaemoglobin because the proposed therapeutic molecule is also the toxic agent. The usable window must be demonstrated for each formulation, disease and route of delivery.
This is why the laboratory evidence can be promising without changing household safety advice. Carbon monoxide from a generator, stove, vehicle or fire is uncontrolled in concentration and duration. It reaches haemoglobin throughout the circulation rather than a selected molecular target.
The same molecule in two settings
Carbon monoxide is chemically spare: one carbon atom, one oxygen atom and a strong bond between them. On an industrial catalyst, that molecule can become a feedstock or a surface-bound intermediate. Space Daily has reported how researchers use carbon monoxide to control fuel-cell catalysts at atomic scale, another setting in which location determines what the molecule does next.
Inside a macrophage recycling an ageing red blood cell, carbon monoxide appears one molecule at a time as haem oxygenase opens the haem ring. Nearby proteins may register its presence, the circulation may carry part of it away, and the lungs will eventually release it into the next breath. The process is regulated by enzymes and limited by the amount of haem being broken down.
In a room with a faulty heater, the direction is reversed. Carbon monoxide arrives from outside, crosses the lungs in bulk and occupies haemoglobin that oxygen needed. The body’s ordinary production and clearance systems were never built to manage that flood.
Somewhere in the liver, spleen or bone marrow, a macrophage is dismantling haem now. An enzyme closes around the ring, oxygen is consumed, iron is freed, biliverdin forms, and one two-atom molecule slips away without colour, smell or sound.