Lecture 3-synthesis Of Amino Acid Derivative Hormones Flashcards
(44 cards)
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)
What can tryptophan be used to do?
The amino acid tryptophan can be modified to form serotonin and melatonin
• Serotonin works through G- protein coupled receptors or ligand gated ion channels
• Melatonin works through G- protein coupled receptors
• Serotonin and melatonin have functions in the body as well as in neurons
Summarize serotonin synthesis
Serotonin is synthesized in the gut, platelets & CNS
• Synthesized from tryptophan
• Serotonin is metabolized to 5-hydroxyindole acetic acid (5-HIAA) by MAO
Outline melatonin formation
Tryptophan—>( 5 hydroxy tryptophan) via tryptophan hydroxylase+ BH4/tetrahydrobiopterin
5 hydroxy tryptophan —> 5 hydroxy tryptamine (serotonin) via amino ac8d decarboxylase + pyridoxal phosphate
Some modifications converts serotonin to melatonin
Monoamine oxidase converts serotonin to 5-HIAA excretion
What is Carcinoid syndrome ?
- Tumor of serotonin producing cells in GIT (APUD cells)
- Cutaneous flushing, sometimes accompanied by sweating
- Gastrointestinal hypermotility causing diarrhea
- Bronchospasm
Increased 5-HIAA excretion in urine
Highlight a serotonin overproduction scenario
Mrs.L began to experience diarrhea and flushing
symptoms, which at first she attributed to menopause.
• Mrs.L went to doctors and specialists, none of whom accurately diagnosed the problem. The symptoms continued in varying degrees until a few months ago
• She soon felt very sick, and a few days later she was admitted to the hospital. That evening, she underwent an emergency bowel resection.
• During 24 hours she had lost four units of blood and woke up to the diagnosis of carcinoid cancer that had metastasized to the liver.”
What does MAO do to serotonin ?
Serotonin is degraded to 5-hydroxyindole acetic acid (5- HIAA) by Monoamine Oxidase (MAO)
How do MAO inhibitors affect Serotonin levels, how does this differ from SSRIs?
- MAO inhibitors have been used to increase serotonin in the CNS
- An important class of antidepressant drugs that works via serotonin
- Slows down degradation of serotonin
Do not confuse MAO inhibitors with selective serotonin reuptake inhibitors (SSRI) • A different class of drug that also functions via serotonin • SSRI increase time that serotonin is in synapse