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