Conversion of norepinephrine to epinephrine occurs by
Ans. a (N-Methylation) (Ref. KDT 6th/pg. 116 and Harper biochemistry 27th/pg. 272)Cells in the adrenal medulla synthesize and secrete epinephrine and norepinephrine. The ratio of these two catechola- mines in humans is roughly 8:1, with 80% of the catecholamine output being epinephrine. Synthesis of catecholamines begins with the amino acid tyrosine, which is taken up by chromaffin cells in the medulla and converted to norepinephrine and epinephrine through the following steps:SYNTHESIS AND SECRETION OF CATECHOLAMINESSTEPS IN CATECHOLAMINE SYNTHESISCatecholamines are synthesized from the amino acid phenylalanine. Tyrosine hydroxylase is the rate limiting enzyme and its inhibition by alphamethyl-p-tyrosine results in depletion of CAs; this can be used in pheochro- mocytoma before surgery and in inoperable cases. All enzymes of CA synthesis are rather nonspecific and can act on closely related substrates, e.g. dopa decarboxylase can form 5-HT from 5-hydroxytryptophan and a methyl DA from a methyl dopa. Synthesis of NA occurs in all adrenergic neurones, while that of Adr occurs only in the adrenal medullary cells. It probably requires high cone of glucocorticoids reaching through intraadrenal portal circulation for induction of the methylating enzyme.# Secretions of Norepinephrine and epinephrine stored in electron-dense granules are stimulated by acetylcholine release from preganglionic sympathetic fibers innervating the medulla.# Many types of "stresses" stimulate such secretion, including exercise, hypoglycemia and trauma.# STEPS:- Tyrosine is transported into catecholamine-secreting neurons and adrenal medullary cells where catecholamine synthesis takes place.- The first step in the process requires tyrosine hydroxylase, which like phenylalanine hydroxylase requires tetrahydrobiopterin (HJB) as cofactor.- The hydroxylation reaction generates DOPA (3,4-dihydrophenylalanine).- DOPA decarboxylase converts DOPA to dopamine, dopamine P-hydroxylase converts dopamine to norepinephrine, and phenylethanolamine.- N-methyltransferase converts norepinephrine to epinephrine.- Tyrosine=> DOPA (HYDROXYLATION)- DOPA=> Dopamine (DECARBOXYLATION)- Dopamine=> Norepinephrine (HYDROXYLATION)- Norepinephrine=> Epinephrine (METHYLATION)# This latter reaction is one of several in the body that uses SAM (S-adenosylhomocysteine) as a methyl donor.ReceptorEffectively bindsEffect of ligand bindingAlpha-1Epinephrine, NorepinephrineIncreased free calciumAlpha-2Epinephrine, NorepinephrineDecreased cyclic AMPBeta-1Epinephrine, NorepinephrineIncreased cyclic AMPBeta-2EpinephrineIncreased cyclic AMP
Methylation
Decarboxylation
Oxidation
Sulphation
Proteins and Amino Acids