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29 Cards in this Set

  • Front
  • Back
What materials are required to make ten out of eleven of the non-essential amino acids?
nitrogen, sulfur, enzymes
Which of the amino acids are converted into neurotransmitters?
glutamate → GABA
tyrosine → catecholamines
tryptophan → serotonin
cysteine → taurine
What are the catecholamines and what are their functions (in general)?
catecholamines are neurotransmitters and hormones; dopamine, norepinephrine, and epinephrine
Where is norepinephrine found?
it is the principal neurotransmitter of postganglionic sympathetic fibers
Where is dopamine founnd?
it is the predominant neurotransmitter of the extrapyramidal system (brain)
Where is epinephrine found?
it is the major hormone of the adrenal medulla (which is an extension of the sympathetic nervous system)
What are the steps of catecholamine biosynthesis (substrates, enzymes, and products)?
1) tyrosine (tyrosine hydroxylase) → 2) DOPA (DOPA decarboxylase) → 3)dopamine (dopamine beta-hydroxylase) → 4) norepinephrine (phenylethanolamine-N-methyl-transferase) → 5) epinephrine
1) ring hydroxylation
2) decarboxylation
3) side-chain hydroxylation
4) N-methylation
What enzyme catalyzes the rate limiting step in catecholamine synthesis?
tyrosine hydroxylase (TH)
What is the cofactor required by tyrosine hydroxylase and what does this cofactor do?
a monooxygenase called tetrahydrobiopterin, uses its electrons to generate oxygen radical intermediate needed to hydroxylate ring
What does nerve stimulation do to tyrosine hydroxylase?
the more a nerve is fired, the more TH will be phosphorylated (TH is activated), and the more TH genes will be expressed
What is the function of aromatic amino acid decarboxylase (AADC) and what does it require to function?
decarboxylates DOPA to form dopamine, requires vitamin B6
What is the function of dopamine (beta) hydroxylase (DBH) and what does it require to function?
hydroxylates (beta) carbon of dopamine to form norepinephrine, requires vitamin C and O2
What is the prodrug, false neurotransmitter that is much like the catecholamine DOPA and what is it used for?
(alpha)-methyldopa, used to treat hypertension
What is the function of phenylethanolamine-N-methyltransferase (PNMT) and what does it require to function?
catalyzes the cytosolic N-methylation of norepinephrine to form epinephrine (in the adrenal medualla), requires S-adenosylhomocysteine (SAMe) as a methyl donor
How is phenylethanolamine-N-methyltransferase (PNMT) regulated?
by cortisol levels (more cortisol increases PNMT activity and improves body's response to acute stress)
What molecule uses hydrogen ion antiport to move catecholamines into vesicles for storage?
vesicular monoamine transporter (VMAT-2)
What establishes the proton gradient for catecholamine uptake via VMAT-2 into vesicles?
ATP-dependent proton translocase
What does binding ATP to catecholamines do to the osmotic effects of the catecholamines?
decreases the neurotransmitter's osmotic effects
How are catecholamines released from the presynaptic neuron?
calcium mediated exocytosis
How are catecholamines returned back into the presynaptic neuron?
NE transporter (NET) (sodium dependent)
What does cocaine do to reuptake of monoamines into the presynaptic neuron?
inhibits reuptake of monoamines norepinephrine, serotonin, and dopamine
How is the activity of epinephrine and norepinephrine terminated?
by reuptake via NET, dilution, transformation
How are catecholamines transformed (inactivated)?
monoamine oxidase (MAO) - oxidatively deaminates
catechol-O-methyl transferase (COMT) - adds a methyl group
What happens to the 30% of NE not taken up into vesicles via VMAT-2 (within presynaptic neuron)?
inactivated by MAO
How are circulating catecholamines cleared and where does this happen?
in the liver and kidney by COMT
Where are MAOs and COMTs found?
MAOs: presynaptic neuron, outer membrane of mitochondria, intestine, liver
COMTs: liver and kidney (cytosol)
What causes Parkinson's Disease?
loss of dopaminergic neurons in the substantia nigra and corpus striatum
How is Parkinson's Disease treated?
L-dopa (dopamine precursor) crosses the blood brain barrier and is converted to dopamine
What is the purpose of taking carbidopa along with L-dopa?
carbidopa increases the efficacy of L-dopa by decreasing metabolism in GI and peripheral tissues