Carbon monoxide metabolism

Lynd, L., Kerby, R., Zeikus, J.G., 1982. Carbon monoxide metabolism of the methylo-trophic acidogen Butyribaclerium methylotrophicum. Journal of Bacteriology 149 (1), 255-263. 

The nervous system is vulnerable to attack from several directions. Neurons do not divide, and, therefore, death of a neuron always causes a permanent loss of a cell. The brain has a high demand for oxy gen. Lack of oxygen (hypoxia) rapidly causes brain damage. This manifests itself both on neurons and oligodendroglial cells. Anoxic brain damage may result from acute carbon monoxide, cyanide, and hydrogen sulfide poisonings. Carbon monoxide may also be formed in situ in the metabolism of dichloromethylene. 

Carbon Monoxide. Figure 1 Heme oxygenase catalyzed heme metabolism (from Pharmacol Rev 57 585-630,... 

The major mono oxygenases in the endoplasmic reticulum are cytochrome P450s—so named because the enzyme was discovered when it was noted that preparations of microsomes that had been chemically reduced and then exposed to carbon monoxide exhibited a distinct peak at 450 nm. Among reasons that this enzyme is important is the fact that approximately 50% of the drugs humans ingest are metabolized by isoforms of cytochrome P450 these enzymes also act on various carcinogens and pollutants. 

Even simple molecules often have strikingly different properties. For example, carbon and oxygen form two different simple compounds. Whereas a molecule of carbon monoxide contains one oxygen atom and one carbon atom, carbon dioxide contains two atoms of oxygen and one atom of carbon. Although these molecules have some common properties (both are colorless, odorless gases), the difference in chemistry caused by a change of one atom is profound. We produce and exhale carbon dioxide as a natural by-product of metabolism. This compound is relatively harmless to humans. In contrast, carbon monoxide is a deadly poison, even at very low concentrations. 

Once the product specifications have been fixed, some decisions need to be made regarding the reaction path. There are sometimes different paths to the same product. For example, suppose ethanol is to be manufactured. Ethylene could be used as a raw material and reacted with water to produce ethanol. An alternative would be to start with methanol as a raw material and react it with synthesis gas (a mixture of carbon monoxide and hydrogen) to produce the same product. These two paths employ chemical reactor technology. A third path could employ a biochemical reaction (or fermentation) that exploits the metabolic processes of microorganisms in a biochemical reactor. Ethanol could therefore also be manufactured by fermentation of a carbohydrate. 

In addition to tobacco smokers, individuals who have had previous exposure to materials containing methylene chloride, such as degreasers, solvents, paint removers, and furniture strippers, are at greater risk because of an existing body burden of carbon monoxide. Approximately one-fourth to one-third of inhaled methylene chloride vapor is metabolized in the liver to carbon monoxide. In addition, methylene chloride is readily stored in body tissue. This stored material is released over time and results in elevated levels of carbon monoxide for extended periods, in some cases more than twice as long as compared with direct carbon monoxide inhalation. 

G10. Gydell, K., Transient effect of nicotinic acid on bilirubin metabolism and formation of carbon monoxide. Acta Med. Scand. 167, 1 (1960). 

Dodds RG, Penney DG, Sutariya BB. 1992. Cardiovascular, metabolic and neurologic effects of carbon monoxide and cyanide in the rat. Toxicol Ixtt 61(2-3) 243-254. 

The electron transfer system has not been studied in detail in fish, but the metabolism of compounds such as biphenyl (37), benzo(a)pyrene (21) and 2,5-diphenyloxazole (38) by fish liver microsomes has been shown to require oxygen and NADPH generating system. The metabolism of BP (21), 2,5-diphenyloxazole (Ahokas, unpublished observation) and aldrin (27.) by fish liver microsomal enzyme system is inhibited strongly by carbon monoxide. This information and the fact that cytochrome P-1+50, as well as NADPH cytochrome c reductase system are present in fish, suggest strongly that fish have a cytochrome P-1+50 mediated monooxygenase system which is very similar to that described in mammals. 

Multiple forms of cytochrome P-1+50. It is now clear that there are more than one form of cytochrome P-1+50. Thomas et al. have recently shown by immunochemical means that there are at least six forms of mammalian cytochrome P-1+50 (39) In 1960 s it was noted that there are at least two catalytically and spectrally distinct cytochrome P-l+50 s, viz. cytochrome P-1+50 and cytochrome P-1+1+8 or P -1+50 (1 0, 1 1). Cytochrome P-1+1+8 is inducible by PAH s such as 3-methylcholanthrene (MC) and BP. It metabolizes preferentially PAH s (such as the above carcinogenic inducers). Cytochrome P-1+1+8 derives its name from the fact that when reduced and complexed with carbon monoxide it has an absorbance maximum at 1+1+8 nm. Cytochrome P-1+50 induced by compounds such as phenobarbital (PB) appears similar to the control cytochrome P-1+50 both spectrally and catalytically. 

Hydrogenases are not the only nickel-containing enzyme, and researchers must therefore compare the maturation of different nickel proteins to obtain an integrated picture of nickel metabolism. Indeed, similarities between some of the hydrogenase-related nickel-processing proteins with urease and carbon monoxide dehydrogenase maturation factors have been noted, and this has facilitated interpretations of the results for... 

Heme metabolized in histiocytes Production of biliverdin releases carbon monoxide (CO)... 

Ahmed AE, Kubic VL, Anders MW. 1977. Metabolism ofhaloforms to carbon monoxide.. In vitro studies. Dmg Metab Dispos 5 198-204. 

Anders MW, Stevens JL, Sprague RW, et al. 1978. Metabolism of haloforms to carbon monoxide, n. In vivo studies. Drug Metab Dispos 6 556-560. 

Stevens JL, Anders MW. 1979. Metabolism of haloforms to carbon monoxide-III. Studies on the mechanism of the reaction. Biochem Pharmacol 28 3189-3194. 

These studies suggest that there are substance(s) in tobacco smoke, as yet unidentified, that inhibit the metabolism of nicotine. Because nicotine and cotinine are metabolized by the same enzyme, the possibility that cotinine might be responsible for the slowed metabolism of nicotine in smokers was examined. In a study in which nonsmokers received an intravenous infusion of nicotine with and without pretreatment with high doses of cotinine, there was no effect of cotinine on the clearance of nicotine (Zevin et al. 1997). Also, carbon monoxide at levels and in patterns similar to those experienced during smoking had no effect on nicotine and cotinine clearance (Benowitz and Jacob 2000). 

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