Noradrenaline (norepinephrine) and adrenaline (epinephrine) synthesis

The very first step in noradrenaline (NA=norepinephrine) synthesis need the synthesis of dopamine from tyrosine. The Dopamine-b-hydroxylase (DbH), an enzyme present in the synaptic vesicle membrane then catalyzes the synthesis of the noradrenaline (norepinephrine) as shown in figure. The NA is actively taken into synaptic vesicles by the vesicular monoamine transporter where it is stored altogether with the ATP.

Figure: Synthesis of norepinephrine and epinephrine. Such catecholamines, such as dopamine, are derived from tyrosine.

For noradrenergic neurons the reactions stop at this position. Though, for relatively few neurons in the hindbrain which are adrenergic (and for the chromaffin cells of the adrenal medulla), the (PNMT) phenyletholamine N-methyltransferase enzyme catalyses the N-methylation of noradrenaline (norepinephrine) to adrenaline (epinephrine).

The high activity by locus coeruleus neurons outcomes in increased expression of the tyrosine hydroxylase genes and de novo synthesis of the enzyme and hence, the demand for NA synthesis can be met. The effect of this is that the DbH becomes the rate limiting enzyme instead of tyrosine hydroxylase; therefore dopamine and its metabolites might be co-released with NA.