Lecture 3-synthesis Of Amino Acid Derivative Hormones Flashcards
How are Catecholamines signaling mechanisms derived?
Via tyrosine
- Phenylalanine
- tyrosine
- L-Dopa
Dopaamine
Norepinephrine
Epinephrine
How is tyrosine obtained by the body?
• Tyrosine is either formed during degradation of phenylalanine, or tyrosine may be consumed in the diet
• Phenylalanine is dietary essential
• As long as phenylalanine is consumed in the diet, tyrosine
is dietary non-essential
• Tyrosine is really just hydroxylated PHE
• L-DOPA is really just PHE that has been hydroxylated twice
What is the function of dopamine?
Primary role as a neurotransmitter in the brain
-Also has signaling roles in the body
What is the role of Norepinephrine?
Primary role as a neurotransmitter for sympathetic nervous system
-Minor role as a hormone, released from adrenal glands
What is the role of epinephrine?
Primary role as a fight or flight hormone
- Sympathetic response
- Released from adrenal gland
What are the types of dopamine receptors in the brain?
Many sub-types of dopamine receptors in the
brain (all are G-proteins)
• Some work through the adenylate cyclase—>cAMP —>PKA pathway
• Might activate or inhibit
• And some…
• Work through the IP3—>DAG—>Ca2+—>PKC pathway
• Depends on the G-protein coupled receptor
how are G receptors structured?
The extracellular domain contains the binding site for a ligand (a hormone or neurotransmitter)
The intracellular domain interacts with G proteins
There are 7 transmembrane a helices
Outline the reactions to convert phenylalanine to epinephrine
Phenylalanine —> tyrosine (phenylalanine hydroxylase+ Tetrahydrobiopterin BH4)
Tyrosine—> DOPA(tyrosine hydroxylase + tetrahydrobiopterin BH4)
DOPA(L-DOPA)—> dopamine (DOPA decarboxylase+ PLP (Vit B6) )
Dopamine—>Norepinephrine (dopamine B-hydroxylase+ Vit. C)
Norepinephrine—> Epinephrine (phenylethanolamine N methyltransferase + S-Adenosyl methionine (SAM)
What is the importance of BH4 in hydroxylation?
BH4 is a cofactors
What is done in decarboxylation in DOPA decarboxylation?
The alpha carboxyl group comes off as carbon dioxide
What is the significance of PNMT in converting norepinephrine to epinephrine?
PNMT-catalyzes a methylation reaction (SAM is the methyl donor)
What is Parkinson disease?
-Neurodegenerative disorder
 Loss of dopamine producing cells in the
basal ganglia
• Characterized by movement disorders: spasticity, tremors, loss of memory, mood disturbances, postural instability
Parkinson disease resulting from not enough formation of a catecholamine molecule (in this case the catecholamine is dopamine, a neurotransmitter)
What is the significance of MAO and COMT?
The catecholamine molecules are degraded by monoamine oxidase (MAO) or catechol-O-methyltransferase (COMT) to form VMA.
Urinary VMA levels may be measured to estimate levels of epinephrine & norepinephrine produced
24-hour test
Whaat does the degradation 9f dopamine form?
HVA- Homovanillic acid (HVA)
What is phaeochromocytoma?
Pheochromocytoma is a tumor found in the adrenal gland
• A 35-year-old husband and father of three children has headaches and palpitations of increasing frequency and severity over the past 6 months.
• Also intense anxiety and panic attacks. His face is often pale and he sweats more.
• Examination reveals he is hypertensive.
• Headache, Sweating, Tachycardia predominant symptoms
Give clinical features used to diagnose pheochromocytoma
- Episodic symptoms
- Characterized by overproduction of epinephrine as a consequence of the tumor
- Adrenal medulla tumor
- Predominant Symptoms include:
- Headache, Sweating, Tachycardia
- Patients have hypertension
- Must use 24-hour urinary measurement • During a symptom episode
All Catecholamines are…
degraded by MAO and COMT
• Norepinephrine and epinephrine are degraded and eventually form VMA
• Urinary VMA levels may be measured to estimate levels of epinephrine & norepinephrine produced
• 24 hour test
• Dopamine is degraded to form homovanillic acid (HVA)