Disease relevance of 3-methyleneindole

• Adducted nucleoside standards were synthesized by the reaction of indole-3-carbinol with each of the four nucleosides under slightly acidic conditions, which catalyze the dehydration of indole-3-carbinol to 3-methyleneindolenine [1].
• To test the hypothesis that a goat lung 2F homologue uniquely catalyzes the dehydrogenation of 3MI to the putative electrophile 3-methylene-indolenine, the CYP2F3 cDNA was cloned from a goat lung cDNA library and expressed in Escherichia coli [2].
• OBJECTIVE: To compare concentrations of 3-methyleneindolenine (3MEIN) in lung tissues obtained from feedlot cattle that died as a result of acute interstitial pneumonia (AIP) and cattle that died as a result of other causes and to compare blood concentrations of 3MEIN in healthy feedlot cattle and feedlot cattle with AIP [3].

High impact information on 3-methyleneindole

• Metabolism of 3-methylindole by vaccinia-expressed P450 enzymes: correlation of 3-methyleneindolenine formation and protein-binding [4].
• The mechanism of 3-methyleneindolenine (3MEI) formation from 3-methylindole (3MI) in goat lung microsomes was examined using stable isotope techniques [5].
• Therefore, CYP2F1 in human bronchial epithelial lung cells may bioactivate 3MI to 3-methyleneindolenine, which induces programmed cell death at relatively low concentrations [6].
• The CYP1A1 and CYP1A2 enzymes produced all three 3 MI metabolites: the dehydrogenation product, 3-methyleneindolenine (V(max)/K(m) = 4 and 22, respectively); the hydroxylation product, indole-3-carbinol (V(max)/K(m) = 42 and 100, respectively); and the epoxidation product, 3-methyloxindole (V(max)/K(m) = 4 and 72, respectively) [7].
• The reconstituted enzyme uniquely catalyzed only the dehydrogenation of 3MI to form 3-methylene-indolenine, an electrophilic intermediate, without detectable formation of other products, thus demonstrating highly unusual selectivity for dehydrogenation rather than hydroxylation of a substrate [2].

Chemical compound and disease context of 3-methyleneindole

• Association of 3-methyleneindolenine, a toxic metabolite of 3-methylindole, with acute interstitial pneumonia in feedlot cattle [3].

Gene context of 3-methyleneindole

• CYP2F1 and CYP2F3 exclusively catalyze the dehydrogenation of 3 MI to 3-methyleneindolenine, without detectable formation of the hydroxylation or epoxidation products [7].

Analytical, diagnostic and therapeutic context of 3-methyleneindole

• Polyclonal antibodies were developed to thioether adducts of 3-methyleneindolenine and were shown by competitive enzyme-linked immunosorbent assay (ELISA) to be highly selective for the detection of 3MI adducts [8].

References