TY - JOUR T1 - Evaluation of the Biochemical Effects Produced <em>in Vivo</em> by Inhibitors of the Three Enzymes Involved in Norepinephrine Biosynthesis JF - Molecular Pharmacology JO - Mol Pharmacol SP - 95 LP - 105 VL - 2 IS - 2 AU - SIDNEY UDENFRIEND AU - PEROLA ZALTZMAN-NIRENBERG AU - ROBERT GORDON AU - SYDNEY SPECTOR Y1 - 1966/04/01 UR - http://molpharm.aspetjournals.org/content/2/2/95.abstract N2 - Inhibitors of tyrosine hydroxylase, dopa decarboxylase, and dopamine-β-oxidase have been compared with respect to the in vivo conversion of tyrosine-14C and dopa-3H to norepinephrine. Tyrosine hydroxylase inhibitors were found to be the most effective in blocking formation of norepinephrine from tyrosine-14C. The lowering of norepinephrine levels in guinea pig tissues by α-methyltyrosine was found to be directly related to the degree of inhibition of tyrosine hydroxylase. Furthermore, with α-methyltyrosine, the measured inhibition of norepinephrine synthesis from tyrosine was found to be exactly the same as the calculated inhibition of tyrosine hydroxylase. This could be true only if tyrosine hydroxylase were the rate-limiting step in the overall biosynthesis of norepinephrine. ACKNOWLEDGMENT The work of R. G. was supported by a Public Health Service Training Grant 51, GM26 from the Division of General Medical Sciences, Public Health Service, Bethesda, Maryland, and is in partial fulfillment of the requirements for the Ph.D. in Pharmacology at George Washington University. ER -