Carbon monoxide

Identification

Name
Carbon monoxide
Accession Number
DB11588
Type
Small Molecule
Groups
Approved, Investigational
Description

Carbon monoxide (CO) is a colorless, odorless, and tasteless gas that has a slightly lower density than air. It is toxic to hemoglobin utilizing animals (including humans), when encountered in concentrations above about 35 ppm, although it is also formed in normal animal metabolism in low quantities, and is thought to have some normal biological/homeostatic functions [10]. Carbon monoxide (CO), is a ubiquitous environmental product of organic combustion, which is also formed endogenously in the human body, as the byproduct of heme metabolism [8]. Exhaled CO (eCO), similar to exhaled nitric oxide (eNO), has been evaluated as a candidate breath biomarker of pathophysiological states, including smoking status, and inflammatory diseases of the lung and other organs. Exhalation of corbon monoxide values have been studied as potential indicators of inflammation in asthma, stable COPD and exacerbations, cystic fibrosis, lung cancer, and during surgery or critical care [10].

A test of the diffusing capacity of the lungs for carbon monoxide (DLCO), is one of the most clinically valuable tests of lung function testing. The technique was first described 100 years ago, and applied to clinical practice many years after. The DLCO measures the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries. The DLCO test is both convenient and simple for the patient to undergo. The ten seconds of breath-holding required for the DLCO maneuver is easier for most patients to perform than the forced exhalation required for other respiratory tests [28].

Carbon monoxide is presently used in small amounts in low oxygen modified atmosphere packaging systems (MAP) for fresh meat to stabilize and maintain natural meat color. This use of CO has been generally recognized as safe (GRAS) in several packaging applications for fresh meat products. Since 2002, FDA has favorably reviewed three GRAS notifications for carbon monoxide use in fresh meat packaging [15]. The FDA classifies this drug as permitted as a food additive in the packaging and preparation of food products, while following the federal code of regulations [12].

There have been several concerns voiced of over the use of carbon monoxide in food products [15], [16], [17]. The European Union has banned the use of carbon monoxide as a color stabilizer in meat and fish. A December 2001 report from the European Commission's Scientific Committee on Food concluded that the gas did not pose a risk provided that food was maintained adequately cold during storage and transport to prevent the growth of microorganisms [16]. In New Zealand, the use of carbon monoxide in fish preparation has been banned, as it may mask the effects of food spoilage and bacterial growth [17].

Structure
Thumb
Synonyms
  • carbon(II) oxide
  • Carboneum oxygenisatum
  • CO
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Carbon Monox, Helium, Oxygen, Nitrogen L.D.M.Carbon monoxide (0.3 %) + Helium (10.5 %) + Nitrogen (67.7 %) + Oxygen (21.5 %)GasRespiratory (inhalation)Praxair, Inc.1993-12-31Not applicableCanada
Carbon Monoxide, Compressed Air Medical G.M.Carbon monoxide (0.3 %) + Medical air (99.7 %)GasRespiratory (inhalation)Praxair, Inc.1993-12-31Not applicableCanada
Co-HE-O2-N2 MixtureCarbon monoxide (0.3 %) + Helium (10.0 %) + Nitrogen (68.7 %) + Oxygen (21.0 %)GasRespiratory (inhalation)Linde Llc1995-12-31Not applicableCanada
Co-NE-O2-N2 MixtureCarbon monoxide (0.3 %) + Neon (0.5 %) + Nitrogen (78.2 %) + Oxygen (21.0 %)GasRespiratory (inhalation)Linde Llc1995-12-31Not applicableCanada
Lung Diffusion Test Mix No Ne CoCarbon monoxide (0.3 %) + Neon (0.5 %) + Nitrogen (78.2 %) + Oxygen (21 %)GasRespiratory (inhalation)Praxair, Inc.1968-12-31Not applicableCanada
Lung Diffusion Test Mix NohcoCarbon monoxide (.3 %) + Helium (10 %) + Nitrogen (68.7 %) + Oxygen (21 %)GasRespiratory (inhalation)Liquid Carbonic Inc.1968-12-311998-06-09Canada
Lung Diffusion Test MixtureCarbon monoxide (.5 %) + Helium (15 %) + Nitrogen (74 %) + Oxygen (23 %)GasRespiratory (inhalation)Matheson Gas Products Canada Inc.1982-12-311997-12-24Canada
Lung Diffusion Test MixtureCarbon monoxide (.4 %) + Medical air (99.99 %)GasRespiratory (inhalation)Matheson Gas Products Canada Inc.1982-12-311997-12-24Canada
Lung Diffusion Test Mixture GasCarbon monoxide (0.1 %) + Helium (10 %) + Nitrogen (68.9 %) + Oxygen (21 %)GasRespiratory (inhalation)Praxair, Inc.1997-05-02Not applicableCanada
Categories
UNII
7U1EE4V452
CAS number
630-08-0
Weight
Average: 28.01
Monoisotopic: 27.99491462
Chemical Formula
CO
InChI Key
UGFAIRIUMAVXCW-UHFFFAOYSA-N
InChI
InChI=1S/CO/c1-2
IUPAC Name
SMILES

Pharmacology

Indication

Used as a marker of respiratory status in spirometry tests [28], [31].

Food additive for pigment fixation in meat [12].

Pharmacodynamics

Carbon monoxide is used to measure the diffusing capacity for carbon monoxide (DLCO), also known as the transfer factor for carbon monoxide. It is a measure of the gas transfer from inspired gas to the circulatory system (red blood cells in particular) [28]. It is used in a particular pulmonary function test called "the single-breath test" [32].

DLCO, measured for clinical and research purposes almost exclusively by the single-breath method is an important and very useful pulmonary function test. It is useful in the evaluation of patients with dyspnea, obstructive lung diseases, restrictive lung diseases, and in patients with diseases of the pulmonary vasculature. The measurement of DLCO using carbon monoxide is representative of the surface area available, the volume of blood present in the pulmonary capillaries, as well as the thickness of the alveolar-capillary membrane [32].

Conditions that increase DLCO: Heart failure, erythrocythemia, alveolar hemorrhage, asthma

Conditions that decrease DLCO: emphysema, pulmonary fibrosis, pulmonary hypertension, pulmonary embolism

In addition to the above uses, carbon monoxide (CO) is increasingly being accepted in recent years as a protective molecule with important signaling capabilities in both physiological/homeostatic and pathophysiological situations. The endogenous production of CO occurs via the activity of constitutive (heme oxygenase 2) and inducible (heme oxygenase 1) heme oxygenase enzymes, which are both responsible for the breakdown of heme. Through the generation of its products, which in addition to carbon monoxide, includes the biliary pigments biliverdin, bilirubin and ferrous iron, the heme oxygenase 1 system also have an essential role in the regulation of the stress response and in cell adaptation to injury. Preclinical studies have suggested potential benefits of carbon monoxide in cardiovascular disease, inflammatory disorders, as well as organ transplantation [3].

Mechanism of action

In respiratory testing, the diffusing capacity for carbon monoxide (DLCO) is a measure of the ability of gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the red blood cells. The DLCO depends not only on the area and thickness of the blood-gas barrier but additionally on the volume of blood in the pulmonary capillaries. The distribution of alveolar volume and ventilation also has an impact on the measurement [29].

DLCO is measured by sampling end-expiratory gas for carbon monoxide (CO) after patients inspire a small and safe amount of exogenous CO, hold their breath, and exhale. Measured DLCO is adjusted for alveolar volume (which is estimated from dilution of helium) and the patient’s hematocrit level. DLCO is reported as mL/min/mm Hg and as a percentage of a predicted value [9].

Carbon monoxide exerts effects on cell metabolism through both hypoxic and non-hypoxic modes of action. Both mechanisms of action are thought to be the result of the ability of carbon monoxide to bind strongly to heme and alter the function and/or metabolism of heme proteins. The binding affinity of carbon monoxide for hemoglobin is more than 200 times greater than that of oxygen for hemoglobin. The formation of carboxyhemoglobin (COHb) decreases the O2 carrying capacity of blood and disrupts the release of O2 from Hb for its use in tissues. Through similar mechanisms, carbon monoxide diminishes the O2 storage in muscle cells by binding to and displacing O2 from, myoglobin. Though all human tissues are vulnerable to carbon monoxide-induced hypoxic injury, those with the highest O2 demand are especially vulnerable, including the brain and heart [26].

Most of the non-hypoxic mechanisms of action of carbon monoxide have been thought to be due to binding of carbon monoxide to heme in proteins other than Hb. The most notable targets of carbon monoxide include components of many important physiological regulatory systems, including brain and muscle oxygen storage and use(myoglobin, neuroglobin); nitric oxide cell signaling (e.g., nitric oxide synthase, guanylyl cyclase); prostaglandin cell signaling (cyclooxygenase, prostaglandin H synthase); energy metabolism and mitochondrial respiration (cytochrome c oxidase, cytochrome c, NADPH oxidase); steroid and drug metabolism (cytochrome P450); cellular redox balance and reactive oxygen species (ROS; catalase, peroxidases); and numerous transcription factors (e.g., neuronal PAS domain protein, NPAS2, implicated in regulation of circadian rhythm) [26].

In meat processing, carbon monoxide reacts with myoglobin, to form carboxymyoglobin, imparting a red appearance to the meat [18].

TargetActionsOrganism
AMyoglobin
deoxidizer
Human
UAlveolar cells
diffusing substance
Human
Absorption

Although CO is not one of the respiratory gases, the similarity of physico-chemical properties of CO and oxygen (O2) permits an extension of the findings of studies on the kinetics of transport of O2 to those of CO. The rate of formation and elimination of COHb, its concentration in blood, and its catabolism is controlled by numerous physical factors and physiological mechanisms [23].

The absorption of carbon monoxide from the consumption treated food products is not significant. Risk of CO toxicity from the packaging process or from consumption of CO-treated meats is negligible [6].

Volume of distribution
Not Available
Protein binding

Binds with very high affinity to hemoglobin in humans [25].

Metabolism
Not Available
Route of elimination
Not Available
Half life

The half-life of carbon monoxide at room air temperature is 3-4 hours. 100% oxygen reduces the half-life to 30-90 minutes; hyperbaric oxygen at 2.5 atm (atmosphere units) with 100% oxygen reduces it to 15-23 minutes [27].

Clearance
Not Available
Toxicity

LD50 is 1807 ppm in rats after 4 hours of exposure [MSDS]. In humans, exposure to 4000 ppm or more in less than 1 hour leads to death [20].

Carbon Monoxide Toxicity from Food Ingestion Treated with Carbon Monoxide

Very little information has been published in the literature on the consumer’s exposure to CO-packaged meat. The toxicological aspects of CO used in MAP of meat were reviewed by Sørheim et al. [7], and they concluded that, with up to about 0.5% of CO, no human toxicity is likely. It has been suggested that the consumption of CO-treated meat is not associated with any health risks, and meat from CO-MAP results only in negligible amounts of CO and COHb in humans [23], [24].

Mechanism of CO Toxicity

Once CO is inhaled, it binds with hemoglobin to form carboxyhemoglobin (COHb) with an affinity of 200 times greater than oxygen that leads to decreased oxygen-carrying capacity and the decreased release of oxygen to tissues, causing tissue hypoxia. Ischemia occurs with CO poisoning when there is a loss of consciousness combined with hypotension and ischemia in the arterial border areas of the brain. Besides binding to many heme-containing proteins, CO interrupts oxidative metabolism, leading to the formation of free radicals. Once hypotension and unconsciousness occur with CO poisoning, lipid peroxidation and apoptosis soon follow [2].

Failure to diagnose CO poisoning may result in morbidity and mortality and allow for continued exposure to a dangerous environment. The management of CO poisoning begins with inhalation of supplemental oxygen therapy and aggressive supportive measures. Hyperbaric oxygen therapy (HBOT) accelerates the dissociation of CO from hemoglobin [1].

The concentration, exposure time and physical activity of the individual will determine the percentage conversion of haemoglobin to carboxyhaemoglobin. The effects produced depend on the degree and duration of saturation of blood with carbon monoxide [20].

Levels of Intoxication with Carbon Monoxide [2]

The first symptoms of carbon monoxide exposure when carboxyhemoglobin is 15-30% are generalized, and may include: headache, dizziness, nausea, fatigue, and impaired manual dexterity. Individuals with ischemic heart disease may suffer from chest pain and decreased exercise duration at COHb levels measured from 1% - 9% [2].

COHb levels between 30-70% lead to loss of consciousness and eventually death [2].

Long-term Effects [2]

Following the resolution of the acute symptoms, there may be a lucid interval from 2-40 days before the development of delayed neurologic sequelae (DNS). Diffuse brain demyelination combined with lethargy, behavioral changes, memory loss, and parkinsonian features may occur. 75% of patients with DNS recover within 1 year. Neuropsychologic abnormalities with chronic CO exposure are found even when magnetic resonance imaging (MRI) and magnetic resonance spectroscopy findings are normal. White-matter damage in the centrum semiovale and periventricular area of the brain, and abnormalities in the globus pallidus, are most commonly observed on MRI following CO toxicity. Though less common, toxic or ischemic peripheral neuropathies are associated with high levels of CO exposure in humans. The basis for the management of CO poisoning is 100% hyperbaric oxygen therapy using a tight-fitting mask for at least 6 hours. The indications for treatment with hyperbaric oxygen to decrease the half-life of COHb remain controversial [2].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
LipegfilgrastimCarbon monoxide may increase the myelosuppressive activities of Lipegfilgrastim.
Food Interactions
Not Available

References

General References
  1. Kao LW, Nanagas KA: Carbon monoxide poisoning. Med Clin North Am. 2005 Nov;89(6):1161-94. doi: 10.1016/j.mcna.2005.06.007. [PubMed:16227059]
  2. Bleecker ML: Carbon monoxide intoxication. Handb Clin Neurol. 2015;131:191-203. doi: 10.1016/B978-0-444-62627-1.00024-X. [PubMed:26563790]
  3. Motterlini R, Otterbein LE: The therapeutic potential of carbon monoxide. Nat Rev Drug Discov. 2010 Sep;9(9):728-43. doi: 10.1038/nrd3228. [PubMed:20811383]
  4. Nikolic I, Saksida T, Mangano K, Vujicic M, Stojanovic I, Nicoletti F, Stosic-Grujicic S: Pharmacological application of carbon monoxide ameliorates islet-directed autoimmunity in mice via anti-inflammatory and anti-apoptotic effects. Diabetologia. 2014 May;57(5):980-90. doi: 10.1007/s00125-014-3170-7. Epub 2014 Feb 2. [PubMed:24488023]
  5. Rochette L, Cottin Y, Zeller M, Vergely C: Carbon monoxide: mechanisms of action and potential clinical implications. Pharmacol Ther. 2013 Feb;137(2):133-52. doi: 10.1016/j.pharmthera.2012.09.007. Epub 2012 Sep 29. [PubMed:23026155]
  6. Djenane D, Roncales P: Carbon Monoxide in Meat and Fish Packaging: Advantages and Limits. Foods. 2018 Jan 23;7(2). pii: foods7020012. doi: 10.3390/foods7020012. [PubMed:29360803]
  7. Sorheim O, Nissen H, Nesbakken T: The storage life of beef and pork packaged in an atmosphere with low carbon monoxide and high carbon dioxide. Meat Sci. 1999 Jun;52(2):157-64. [PubMed:22062367]
  8. Ryter SW, Choi AM: Carbon monoxide in exhaled breath testing and therapeutics. J Breath Res. 2013 Mar;7(1):017111. doi: 10.1088/1752-7155/7/1/017111. Epub 2013 Feb 27. [PubMed:23446063]
  9. Hu HJ, Sun Q, Ye ZH, Sun XJ: Characteristics of exogenous carbon monoxide deliveries. Med Gas Res. 2016 Jul 11;6(2):96-101. doi: 10.4103/2045-9912.184719. eCollection 2016 Apr-Jun. [PubMed:27867475]
  10. CARBON MONOXIDE [Link]
  11. Therapeutic Applications of Carbon Monoxide [Link]
  12. FDA Federal Code of Regulation Document [Link]
  13. Diverse Pharmacological Effects of Carbon Monoxide-Releasing Molecules [Link]
  14. Carbon Monoxide: Endogenous Production, Physiological Functions, and Pharmacological Applications [Link]
  15. Regulatory Status of Carbon Monoxide for Meat Packaging [Link]
  16. FDA Is Urged to Ban Carbon-Monoxide-Treated Meat [Link]
  17. NZ document, carbon monoxide in fish [Link]
  18. Subscribe to our FREE newsletter Subscribe FDA asked to rescind use of carbon monoxide for meats [Link]
  19. Modified Atmosphere Packaging (MAP): Microbial Control and Quality [Link]
  20. Afrox Carbon Monoxide MSDS [Link]
  21. Myoglobin Chemistry and Meat Color [Link]
  22. WHO document, toxokinetics of CO [Link]
  23. Pharmacokinetics and Mechanisms of Action of Carbon Monoxide [Link]
  24. METMYOGLOBIN REDUCTION IN BEEF SYSTEMS AS AFFECTED BY AEROBIC, ANAEROBIC AND CARBON MONOXIDE‐CONTAINING ENVIRONMENTS [Link]
  25. The binding of carbon monoxide to hemoglobin [Link]
  26. CDC toxicological Profile for Carbon Monoxide [Link]
  27. Carbon Monoxide Toxicity [Link]
  28. Diffusing capacity for carbon monoxide [Link]
  29. Merck Manuals, Diffusing Lung Capacity [Link]
  30. Praxair website [Link]
  31. The carbon monoxide diffusing capacity [File]
  32. 2017 ERS/ATS standards for single-breath carbon monoxide uptake in the lung [File]
External Links
Human Metabolome Database
HMDB0001361
KEGG Drug
D09706
KEGG Compound
C00237
PubChem Compound
281
PubChem Substance
347827995
ChemSpider
275
ChEBI
17245
ChEMBL
CHEMBL1231840
HET
CMO
Wikipedia
Carbon_monoxide
PDB Entries
1a6g / 1a9w / 1abs / 1aj9 / 1ajg / 1ajh / 1bbb / 1bzr / 1cbm / 1cg8
show 333 more
MSDS
Download (144 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentRespiratory Distress Syndrome, Adult1
1RecruitingOtherEndothelial Dysfunction1
1TerminatedTreatmentHealthy Volunteers1
1, 2WithdrawnTreatmentPulmonary Hypertension (PH)1
2Active Not RecruitingTreatmentIdiopathic Pulmonary Fibrosis (IPF)1
2CompletedTreatmentPulmonary Disease, Chronic Obstructive1
2TerminatedTreatmentIleus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
GasRespiratory (inhalation)
Prices
Not Available
Patents
Not Available

Properties

State
Gas
Experimental Properties
PropertyValueSource
boiling point (°C)-191.5MSDS
Predicted Properties
PropertyValueSource
Water Solubility6.37 mg/mLALOGPS
logP-0.06ALOGPS
logS-1.1ALOGPS
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity26.23 m3·mol-1ChemAxon
Polarizability1.94 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Mass Spectrum (Electron Ionization)MSsplash10-004i-9000000000-dfbb2bd73fc3d527a340
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of inorganic compounds known as homogeneous other non-metal compounds. These are inorganic non-metallic compounds in which the largest atom belongs to the class of 'other non-metals'.
Kingdom
Inorganic compounds
Super Class
Homogeneous non-metal compounds
Class
Homogeneous other non-metal compounds
Sub Class
Not Available
Direct Parent
Homogeneous other non-metal compounds
Alternative Parents
Not Available
Substituents
Homogeneous other non metal
Molecular Framework
Not Available
External Descriptors
one-carbon compound, carbon oxide (CHEBI:17245) / a small molecule (CARBON-MONOXIDE)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Deoxidizer
General Function
Oxygen transporter activity
Specific Function
Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles.
Gene Name
MB
Uniprot ID
P02144
Uniprot Name
Myoglobin
Molecular Weight
17183.725 Da
References
  1. Djenane D, Roncales P: Carbon Monoxide in Meat and Fish Packaging: Advantages and Limits. Foods. 2018 Jan 23;7(2). pii: foods7020012. doi: 10.3390/foods7020012. [PubMed:29360803]
2. Alveolar cells
Kind
Group
Organism
Human
Pharmacological action
Unknown
Actions
Diffusing substance
References
  1. Diffusing capacity for carbon monoxide [Link]
  2. Merck Manuals, Diffusing Lung Capacity [Link]

Drug created on April 28, 2016 12:59 / Updated on October 01, 2018 15:02