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    1. The document outlines the biosynthesis, storage, release, and metabolism of catecholamines (CAs). It describes the pathways from amino acids to dopamine, norepinephrine, and epinephrine, as well as their catabolism via monoamine oxidase enzymes and methyltransferases. 2. Possible abnormalities in CA metabolism include deficiencies in enzymes like phenylalanine hydroxylase which can lead to toxic buildup of amino acids. Inhibitors and stimulants of various enzymes in the pathways are mentioned. 3. The document discusses the 5 major types of CA receptors, which are G-protein coupled, and how their activity can increase or decrease cyclic AMP synthesis. It also

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    1. The document outlines the biosynthesis, storage, release, and metabolism of catecholamines (CAs). It describes the pathways from amino acids to dopamine, norepinephrine, and epinephrine, as well as their catabolism via monoamine oxidase enzymes and methyltransferases. 2. Possible abnormalities in CA metabolism include deficiencies in enzymes like phenylalanine hydroxylase which can lead to toxic buildup of amino acids. Inhibitors and stimulants of various enzymes in the pathways are mentioned. 3. The document discusses the 5 major types of CA receptors, which are G-protein coupled, and how their activity can increase or decrease cyclic AMP synthesis. It also

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    2 views2 pages

    Synaptic Communication With Catecholamines

    Uploaded by

    kep1313
    1. The document outlines the biosynthesis, storage, release, and metabolism of catecholamines (CAs). It describes the pathways from amino acids to dopamine, norepinephrine, and epinephrine, as well as their catabolism via monoamine oxidase enzymes and methyltransferases. 2. Possible abnormalities in CA metabolism include deficiencies in enzymes like phenylalanine hydroxylase which can lead to toxic buildup of amino acids. Inhibitors and stimulants of various enzymes in the pathways are mentioned. 3. The document discusses the 5 major types of CA receptors, which are G-protein coupled, and how their activity can increase or decrease cyclic AMP synthesis. It also

    Copyright:

    Attribution Non-Commercial (BY-NC)
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    Synaptic Communication with Catecholamines (CA) April 5, 2010 1. Outline the biosynthesis, storage, release, and metabolism of CA.

    a. BIOSYNTHESIS
    CA Phenylalanine tyrosine Enzyme Phenylalanine hydroxylase Clinical significance PKU: deficiency in enzyme; build up of Phe (toxic to brain) Alpha-methyltyrosine, iron chelators, and lead: inhibit TH Additional info Majority of tyrosine is obtained from eating highprotein foods Regulation of TH: short-term: phosphorylation & dephosphorylation long-term: transcription (stimulated by neurotransmitters, hormones, caffeine, and nicotine)

    Tyrosine LDopa

    Tyrosine hydroxylase

    L-Dopa dopamine

    DOPA decarboxylase (also AAADC, which produces 2PEA) Dopamine betahydroxylase

    AAADC activity increased in schizophrenia; stimulated by amphetamines, LSD NE is target for treating depression, anxiety, etc NE function: sleep, arousal, attention, vigilance, learning

    DA Norepinephrine

    NE Epinephrine

    Phenylethylamine -N-methyl transferase

    Epi functions: increased sympathetic activity

    b. CATABOLISM i. Enzymes: 1. Monoamine oxidases MAO (types A and B) a. Genes: X chromosome b. Inhibitors i. MAO-A: gene mutation causes abnormal and violent behavior

    ii. MAO-B: 1-Deprenyl, smoking (nicotine facilitates DA release) iii. *Pargyline: inhibitor of MAO 2. CA-O-methyltransferases (COMT) a. Inhibitors used to treat Parkinsons ii. Products: 1. DA homovanillic acid (HVA) 2. NE 3-methyl-4-hydroxyphenol-glycol (MHPG) 2. Discuss possible abnormalities in CA metabolism a. See #1

    3. Discuss the CA receptors and their regulation


    CA Dopamine Release Released from synaptic vesicles after Ca2+ permeability increases Receptor 5 major types; G-coupled 1&5: activate cAMP synthesis 2-4: inhibit synthesis Reuptake DA transporter (DAT): reuptake of DA by presynaptic neuron **Inhibited by cocaine (more DA in the cleft) and amphetamines (release DA and block its reuptake)

    Norepinephri ne/ epinephrine

    Released from postsynaptic adrenergic neurons

    Alpha1, alpha 2 Beta: agonists used to treat asthma; antagonists used to treat social phobias/stage fright (e.g. propranolol)

    4. Discuss how the Human Genome Project will help to choose pharmacological treatment options based on exact science a. Intrastriatal injection of an adenoviral vector expressing glial-cell-linederived neurotrophic factor prevents dopaminergic neuron degeneration and behavioral impairment in a rat model of Parkinson disease

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