Abstract
Erythromycin is rapidly demethylated by a microsomal enzyme of rabbit liver to yield des-N-methyl erythromycin and formaldehyde. Formaldehyde was derived from the N-methyl group of D-desosamine exclusively, none coming from the O-methyl group of L-cladinose. The enzyme is most abundant in liver. Other tissues do not demethylate the antibiotic, with the exception of the adrenal gland which showed some demethylating activity. The distribution of the enzyme and its cofactor requirements indicate that it is similar to enzymes that demethylate other alkylamines. Specificity of the enzyme is rather low, since a number of derivatives of erythromycin can be demethylated. End products from demethylation of erythromycin and 2′-propionyl erythromycin, and their possible intermediates, are discussed.
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