Acetylenes, oxidation metabolism

The major metabolic pathway of terminal acetylenic derivatives is via oxidation to the corresponding acetic acid derivatives. Thus, Sullivan and coworkers and Wade and coworkers showed in 1979 that the major metabolites of ethynylbiphenyls in the rat were biphenyl-4-yl acetic acids. These metabolites are further oxidized to 4 -hydroxybiphenyl-4-yl acetic acids before being excreted in the urine (Scheme 4). Because the in vitro metabolism of biphenylacetylenes by rat liver microsomes requires nicotine-adenine-dinucleotide phosphate (NADPH) and molecular oxygen and is inhibited by carbon monoxide, it was concluded that the oxidative metabolism of the acetylenes to the corresponding acetic acid derivatives is mediated by cytochrome P450 . Acetic acid... 

Trichloroethane is oxidized to 2,2,2-trichlor-oethanol and trichloroacetic acid by the cytochrome P450 mixed-function oxidase system, which are excreted in the urine while unchanged 1,1,1-trichloroethane, carbon dioxide, and acetylene are excreted in expired air. It is estimated that less than 7% of 1,1,1-trichloroethane is absorbed and metabolized by any exposure route and the toxicokinetic behavior is qualitatively identical across all species. Less than 1% of 1,1,1-trichloroethane remains in the human body after 9 days. 1,1,2-Trichloroethane is metabolized to... 

Substances that have terminal double or triple bonds, if unconjugated to other multiple bonds, are oxidized by P-450 in the e.r. to toxic substances which attack this porphyrin and deactivate it. Examples are ethylene, acetylene, vinyl chloride and the hypnotic ethchlorvynol which is l-chloro-3-ethylpent-l-en-4-yn-3-ol. Thus, ethylene leads to the A-2-hydroxyethy 1-derivative of P-450. A further adverse effect is that other drugs, if given at the same time, escape the usual metabolic transformation and so build up in the patient (Ortiz de Montellano, Beilan and Matthews, 1982). 

In the biosynthesis of metabolically altered acetylenic compounds, various numbers of acetylenic bonds may be inserted and the chain shortened by a- or p-oxidation or both (Fig. 3.3). Triple bonds are usually introduced in a conjugated manner, although they may be separated by a methylene group from the initial double bond of oleic acid. Other compounds maintain the Z double bond and do not undergo an allylic rearrangement (Jente et al., 1988). 

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