How a Single Molecule Crafts Carbon Monoxide
When we think of carbon monoxide (CO), most of us picture a deadly, odorless gas—a silent killer that claims hundreds of lives each year. But behind this toxic reputation lies an astonishing biological truth: our own bodies carefully craft this same molecule, producing it in precise amounts where it serves as a crucial signaling molecule with profound effects on our health.
Our cells produce CO intentionally through specialized enzymatic processes, maintaining precise concentrations for signaling purposes.
Understanding CO biosynthesis has implications for treating conditions ranging from malaria to organ transplant rejection.
Heme is an iron-containing porphyrin—a flat, ring-like structure that cradles an iron atom at its center. This unassuming molecular arrangement is one of life's most crucial designs.
Heme forms the active core of hemoglobin, the protein in red blood cells that carries oxygen from our lungs to every tissue in the body. Without heme, oxygen transport as we know it would be impossible.
Heme Molecule
Iron-containing porphyrin structureThe same heme molecule temporarily associates with the heme oxygenase enzyme and provides the catalytic center where the chemical transformation occurs 1 .
| Product | Role in the Body | Significance |
|---|---|---|
| Carbon Monoxide (CO) | Signaling molecule that influences blood vessel dilation, inflammation, and cell death | Helps regulate blood pressure, immune responses, and may protect tissues from damage |
| Biliverdin/Bilirubin | Powerful antioxidants that neutralize harmful reactive oxygen species | Protects cells from oxidative stress and damage |
| Iron | Essential mineral recycled for use in new proteins | Conserves iron resources and reduces the need for dietary iron |
The emergency response team that ramps up production in response to cellular stress, inflammation, or the presence of excess heme .
The maintenance crew that provides a steady baseline of activity, particularly abundant in the brain and testes .
The heme ring is first hydroxylated (adds an oxygen and hydrogen) at the α-methane bridge, creating α-hydroxyheme.
The modified heme now has its α-bridge carbon removed entirely, releasing that carbon as carbon monoxide and forming the green pigment biliverdin while releasing iron.
Biliverdin is quickly converted to bilirubin by another enzyme, completing the transformation .
While much heme oxygenase research focuses on animals, an elegant experiment with plants provides excellent insight into how scientists study this system. Researchers developed a sensitive method to detect and measure the carbon monoxide produced when plant tissues break down heme 7 .
Fresh plant tissues from spinach leaves and potato tubers were homogenized and separated into soluble and particulate fractions.
The plant preparations were incubated with heme and NADPH in phosphate buffer under controlled conditions.
Carbon monoxide production was measured using gas chromatography with reduction gas detection 7 .
| Plant Tissue | Type of Tissue | Relative CO Production Rate | Chloroplast Presence |
|---|---|---|---|
| Spinach Leaf | Green, photosynthetic |
|
Yes |
| Potato Tuber | Non-photosynthetic |
|
No |
| Onion Bulb | Storage organ |
|
No |
| Carrot Root | Storage root |
|
No |
| Condition Tested | Optimal Value | Effect on CO Production |
|---|---|---|
| Heme Concentration | 50 μM | Initial rapid increase, then gradual rise up to 600 μM |
| NADPH Concentration | 1.0 mM | Steady increase up to 1.0 mM, then plateau |
| Temperature | 37°C | Peak activity at 37°C, sharp decline above 45°C |
| pH | 7.4-8.0 | Moderate activity at neutral pH, peak in slightly basic conditions |
| Light vs. Dark | Dark conditions | 25-35% higher production in the dark |
Studying the heme oxygenase system requires specialized tools and approaches. Here are some key reagents and materials that researchers use to unravel the mysteries of CO production:
| Reagent/Material | Function in Research | Example from Search Results |
|---|---|---|
| Methemalbumin (MHA) | Provides a soluble, biologically relevant form of heme as substrate for HO enzymes | Used as heme source in plant CO production studies 7 |
| NADPH | Serves as essential electron donor for the HO enzymatic reaction; required for all three oxidation steps | Included in reaction mixtures to support enzymatic activity 7 |
| Gas Chromatography with Reduction Gas Detection | Enables sensitive detection and quantification of CO production from heme breakdown | Capable of detecting as little as 1 pmol of CO, crucial for measuring activity in heterogeneous plant preparations 7 |
| Phosphate Buffer | Maintains optimal pH environment for enzymatic activity | Used at 0.1 M concentration, pH 7.4 for plant HO-like activity 7 |
| Carbon Monoxide-Releasing Molecules (CORMs) | Pharmaceutical compounds that deliver controlled amounts of CO to study its biological effects or potential therapeutic benefits | Investigated as potential treatments for lung injury, sepsis, and transplantation complications |
The discovery that our bodies intentionally produce carbon monoxide represents a major shift in our understanding of this molecule. CO is now recognized as one of three "gasotransmitters"—gaseous molecules that our cells use to communicate, alongside nitric oxide and hydrogen sulfide 6 .
Relaxing blood vessels to regulate blood pressure
Calming overactive immune responses
Protecting against unnecessary cell suicide
Helping to maintain our biological clock 6
Carbon Monoxide
Nitric Oxide
Hydrogen Sulfide
Carefully controlled low-dose CO inhalation is being investigated for conditions including kidney injury, heart ischemia-reperfusion damage, and inflammatory bowel disease 6 .
Finding ways to safely boost the body's own HO-1 expression could help in situations where enhanced heme breakdown and CO production would be beneficial, such as in malaria infection 4 .
The story of heme's dual role as both cofactor and substrate in carbon monoxide biosynthesis showcases nature's breathtaking efficiency. In a single molecular arrangement, our bodies have solved multiple problems simultaneously: disposing of potentially toxic heme, recycling valuable iron, generating protective antioxidants, and producing a precise signaling molecule—all through one elegant system.
This biochemical double duty reminds us that in biology, simplicity often underlies apparent complexity. The heme molecule, which first appeared in ancient life forms, has been leveraged and repurposed through evolution to serve multiple critical functions. As research continues to unravel the intricacies of the heme-heme oxygenase-carbon monoxide system, we can expect new insights into human health and disease, and potentially new therapies that harness this elegant piece of molecular machinery.
The next time you hear about carbon monoxide, remember that beyond its dangerous reputation lies a fascinating biological molecule with a crucial role in our bodies—all thanks to the double life of an iron-containing ring called heme.