Abstract

Transformations of l-dopa and its metabolites have been examined in germ-free and conventional rats and in mixed cultures of rat caecal contents. m-Hydroxyphenylacetic acid appears in the urine of conventional animals but not germ-free rats fed l-dopa or dopamine. Since germ-free and conventional rats both readily convert m-tyramine to m-hydroxyphenylacetic acid, it appears that germ-free rats cannot convert dopamine to m-tyramine. This observation and the demonstration of the conversion of dopamine to m-tyramine in mixed cultures of rat caecal contents indicate that the dehydroxylation at the para position of dopamine can be attributed to the intestinal microflora of the rat. Similar evidence supports the bacterial conversion of 3, 4-dihydroxyphenylacetic acid to m-hydroxyphenylacetic acid. A third dehydroxylation at the para position in the metabolism of dopa leads to the formation of m-hydroxyphenylpropionic acid. The substrate for this p-dehydroxylation reaction is not known but the overall transformation can be found in conventional rats and caecal cultures but not in germ-free rats. Several metabolites of l-dopa found in the conventional rat appear in anaerobic cultures of rat caecal contents. Nevertheless, intermediates in l-dopa metabolism by the rat, e.g., dopamine and m-tyramine, are not further metabolized in culture and therefore can be exeluded as intermediates in exclusively bacterial metabolism. Thus bacteria complement the mammalian reactions but are also capable of directing dopa metabolism toward alternative metabolic pathways.