Adrenergic Neurotransmitters Overview

Adrenergic Neurotransmitters

• Norepinephrine (NE), Epinephrine (E), and Dopamine (DA) are catecholamines (CAs).
• Catecholamines are organic compounds containing a catechol nucleus (ortho-dihydroxybenzene) and an ethylamine group.
• Epinephrine is polar and soluble in water due to its three hydroxyl groups.
• Biosynthesis of Catecholamines
• Step 1: Tyrosine Hydroxylase (TH) catalyzes the hydroxylation of L-tyrosine to L-DOPA.
• TH requires molecular oxygen, Fe2+, and a tetrahydropteridine cofactor.
• TH is the rate-limiting step in CA biosynthesis.
• TH inhibitors include -methyl-p-tyrosine, -methyl-3-iodotyrosine, and -methyl-5-hydroxytryptophan.
• Step 2: L-aromatic amino acid decarboxylase (AADC) decarboxylates L-DOPA to dopamine.
• AADC is not specific to L-DOPA.
• Parkinsonism is characterized by dopamine deficiency in the brain.
• L-DOPA (levodopa) is a prodrug that enters the brain and is decarboxylated to dopamine.
• Peripheral AADC inhibitors like carbidopa can reduce systemic side effects of L-DOPA.
• Step 3: Dopamine β-hydroxylase (DBH) hydroxylates dopamine to norepinephrine.
• DBH is located inside vesicles.
• Dopamine is transported into vesicles by the vesicular monoamine transporter (VMAT).
• Step 4: Phenylethanolamine-N-methyltransferase (PENMT) catalyzes the N-methylation of norepinephrine to epinephrine.
• PENMT is a cytosolic enzyme.
• S-adenosyl methionine (SAM) is required as a methyl donor.
• Storage, Release, Uptake, and Metabolism
• Catecholamines are stored in vesicles.
• Release occurs through exocytosis triggered by nerve impulses.
• Reuptake into the presynaptic neuron is the primary mechanism of termination.
• Metabolism involves enzymatic breakdown to inactive metabolites.

Figure: Biosynthesis of Dopamine, Norepinephrine, and Epinephrine

• This figure visually represents the sequential steps involved in the synthesis of dopamine, norepinephrine, and epinephrine, highlighting the enzymes and substrates involved.

Figure: Model of Life Cycle of Norepinephrine

• This figure provides a schematic representation of the complete life cycle of norepinephrine, encompassing its synthesis, storage, release, reuptake, and metabolism.

Explore the key concepts surrounding adrenergic neurotransmitters, including norepinephrine, epinephrine, and dopamine. This quiz delves into the biosynthesis of catecholamines, the role of tyrosine hydroxylase, and the implications of dopamine deficiency. Gain insights into the biochemical processes that underlie these important neurotransmitters.