Podcast
Questions and Answers
Which of the following is the correct sequence of events in the -adrenergic pathway?
Which of the following is the correct sequence of events in the -adrenergic pathway?
What is the primary effect of catecholamines on fuel metabolism in the liver?
What is the primary effect of catecholamines on fuel metabolism in the liver?
Which of the following amino acids is the second most important substrate for hepatic gluconeogenesis after alanine?
Which of the following amino acids is the second most important substrate for hepatic gluconeogenesis after alanine?
Which of the following is the correct sequence of events in the synthesis of epinephrine?
Which of the following is the correct sequence of events in the synthesis of epinephrine?
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Which of the following is the primary enzyme responsible for the degradation of norepinephrine?
Which of the following is the primary enzyme responsible for the degradation of norepinephrine?
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In which of the following tissues does the -adrenergic pathway occur?
In which of the following tissues does the -adrenergic pathway occur?
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Study Notes
Hydroxylation of Dopamine
- Substrate: Dopamine
- Enzyme: Dopamine β-hydroxylase
- Cofactors: Vitamin C, O2
- Product: Norepinephrine
Methylation of Norepinephrine
- Substrate: Norepinephrine
- Enzyme: Phenylethanolamine N-methyltransferase (PNMT)
- Cofactors: SAM or AdoMet (methyl-group donors)
- Product: Epinephrine (Adrenaline)
Mechanism of Action of Epinephrine (β-Adrenergic Pathway)
- Occurs in muscles, adipose tissue, and liver
- Epinephrine binds with membrane-bound heptahelical GPCR
- GDP in the α-subunit is replaced by GTP, activating Adenylate cyclase
- Adenylate cyclase catalyzes the synthesis of cAMP from ATP
- cAMP activates cytoplasmic PKA and MAPK
- Activated PKA and MAPK activate transcription factors (e.g., CREB, AP-1, ETSF) for various metabolic and physiologic effects
Catabolic Pathway of Norepinephrine
- 1st Pathway: Oxidative deamination by Monoamine oxidase (MAO) → NH4+ is removed from Norepinephrine
- Aldehyde product undergoes oxidation and forms 3,4-dihydromandelic acid
- 3,4-dihydromandelic acid is methylated into Vanillylmandelic acid (VMA) by Catechol-o-methyltransferase (COMT)
- 2nd Pathway: Direct methylation by COMT → Norepinephrine is methylated into Normetanephrine, then deaminated by MAO to yield VMA
Effects of Epinephrine and Norepinephrine on Fuel Metabolism
- In adipose tissue: release of catecholamines promotes TAG degradation, leading to fatty acid β-oxidation and glycerol substrate for hepatic gluconeogenesis
- In the liver: increased gluconeogenesis and glycogenolysis, leading to hyperglycemia
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Description
Test your knowledge on the biosynthesis of catecholamines such as dopamine, norepinephrine, and epinephrine, as well as the mechanism of action of epinephrine through the β-adrenergic pathway. Understand the enzymes, cofactors, substrates, and products involved in these processes.
