Adrenaline
Biosynthesis and regulation
Parenteral administration of adrenaline to acute-care cardiac patients can produce plasma concentrations of 10,000 to 100,000 ng/L. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines. Adrenaline is synthesized in the chromaffin cells of the adrenal medulla of the adrenal gland and a small number of neurons in the medulla oblongata in the brain through a metabolic pathway that converts the amino acids phenylalanine and tyrosine into a series of metabolic intermediates and, ultimately, adrenaline. Tyrosine is first oxidized to L-DOPA by Tyrosine hydroxylase, this is the rate-limiting step. Then it is subsequently decarboxylated to give dopamine by DOPA decarboxylase (aromatic L-amino acid decarboxylase). Dopamine is then converted to noradrenaline by dopamine beta-hydroxylase which utilizes ascorbic acid (Vitamin C) and copper. The final step in adrenaline biosynthesis is the methylation of the primary amine of noradrenaline. This reaction is catalyzed by the enzyme phenylethanolamine N-methyltransferase (PNMT) which utilizes S-adenosyl methionine (SAMe) as the methyl donor. While PNMT is found primarily in the cytosol of the endocrine cells of the adrenal medulla (also known as chromaffin cells), it has been detected at low levels in both the heart and brain.
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