ELUCIDATION OF THE RATE-LIMITING STEP IN NOREPINEPHRINE BIOSYNTHESIS IN THE PERFUSED GUINEA-PIG HEART
- Laboratory of Clinical Biochemistry and the Experimental Therapeutics Branch, National Heart Institute, National Institutes of Health, Bethesda, Maryland
Abstract
Guinea-pig hearts were perfused with varying concentrations of the norepinephrine precursors, tyrosine, 3,4-dihydroxyphenylalanine (dopa) and 3,4-dihydroxyphenethylamine (dopamine). With all three precursors the rate of norepinephrine synthesis increased as the concentration in the perfusion fluid increased. However, only with tyrosine were maximal rates achieved (0.2 µg/g/hr) at concentrations below 5 x 10 -4 M. The apparent Km for the overall reaction (tyrosine → norepinephrine) was found to be comparable to that observed for conversion of tyrosine to dopa by purified tyrosine hydroxylase ( 2 x 10 -5 M). These and other factors indicate that conversion of tyrosine to dopa is the rate-limiting step in the formation of norepinephrine in the sympathetic nervous system.
Although ascorbic acid has been shown to be a requirement for purified dopamine-β-oxidase activity severe seurvy did not diminish the ability of isolated heart to form norepinephrine from tyrosine or dopamine.
- The Williams & Wilkins Comapny
