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Cell Biology, NOTE Signaling Receptors:…

- - - - Signaling Molecules/Ligands
        Signaling Molecule/Ligands are first messengers.
        Ligands are the first messengers.
        Differentiate between the 2 Types of Signaling Molecules/Ligands
        Signaling Molecules of 1st messengers.
        
        Ligands (amino acids & protein) that directly bind to receptors:
        
        1.1. Membrane permeable
        Small Hydrophobic molecules that bind to intracellular receptors.
        Eg: Steroid and Thyroid hormone.
        
        1.2. Non-Membrane Permeable
        Ligands bind to receptors on the cell surface.
        Eg: Proteins and Neurotransmitters.
        
        Ligands that diffuse across the membrane and bind directly to the target
        
        Directly target and regulate activity of intracellular enzymes.
        Eg: Nitric Oxide and Carbon Dioxide
        
        List the Type of Receptors:
        
        Intracellular Receptors
        
        Plasma Membrane Receptor
        
        Intracellular Receptors
        Some receptor proteins are intracellular ( either in cytosol or nucleus)
        Membrane Permeable small, hydrophobic molecules bind to and activate intracellular receptors.
        Eg: Steroids, Thyroid hormones, Vitamin D3
        
        Plasma Membrane Receptors
        Most receptor proteins are with in the plasma membrane.
        Non-membrane permeable water-soluble molecules bind to specific sites on the receptors.
        Eg: Amino acid and Protein derived hormones.
        There are three major classes of membrane receptors:
        G-Protein Linked Receptors
        Enzyme Linked Protein Receptors
        Ion Channel receptors
        
        G-Protein Linked Receptors
        Largest family of cell surface receptors.
        These are Receptors for Epinephrine, and Glucagon, and Serotonin
        The G-protein linked receptors function with the help of the G-Protein.
        G-Protein acts as an on/off switch.
        If GDP is bound to the G-Protein then G-Protein in inactive.
        
        Enzyme-Linked Receptors
        Enzyme-Linked Receptors are cell membrane receptors with an intracellular domain linked to an enzyme
        In some cases the intracellular domain is the enzyme that catalyses a reaction.
        Receptors Tyrosine Kinase (RTK) are a class of enzyme-linked receptors.
        A kinase is an enzyme that delivers phosphate groups to a protein or other targets (Phosphorylation)
        And a RTK (Receptor Tyrosine Kinase) deliver phosphate groups specifically to Amino Acid Tyrosine.
        Eg: these are receptors for most growth and insulin
        
        Ion Channel Receptors
        Ion channel receptors act like a gate.
        A signal molecule will bind to the receptor.
        A channel in the receptor will open allowing specific ions to pass through, such as Sodium and Calcium ions.
        Examples: Muscle Contraction
- - - - Step 2 : Transduction
        2nd messenger are intracellular molecules or ions that diffuse to protein targets.
        Eg: cyclic AMP (cAMP), Inositol Phosphates, cGMP and Ca2+
        Two principles pathways involving the GPCR are:
        cAMP And Phosphatidylinositol signaling pathways.
        There is a large number of 1st messenger, but a few intracellular 2nd messengers.
        Whys? For greater coordination and regulation.
        
        Describe The cAMP Pathway
        cAMP is a widely used 2nd messenger pathway.
        The target protein for the cAMP pathway is the: Protein Kinase A.
        The Cellular Response of Protein Kinase A when stimulated by cAMP is in the lungs and muscles.
        Lungs: Adrenalin causes smooth muscles to relax, bronchodilation.
        Muscles: Adrenalin causes a glycogen breakdown.
        How can you regulate the cAMP Pathway ?
        By using molecules that increase cAMP levels:
        Cholera toxin
        Caffeine
        Pertussis Toxin
        Phosphodiesterase Inhibitors
        
        Describe the Phosphatidylinositol Pathway
        Inositol Phosphate
        When Phospholipids called Phosphatidylinositols are phosphorylated they are split into half releasing two fragments that both act as second messengers.
        These are IP3 and DAG.
        Process:
        
        A signal molecule binds to a receptor leading to the activation of Phospholipase C
        
        Phospholipase C cleaves a plasma membrane Phospholipid called PIP2 into DAG and IP3
        
        DAG functions as a 2nd messenger in other pathways.
        
        IP3 quickly diffuses through the cytosol and bind to an IP3-Gated Calcium Channel in the ER membrane, causing it to open.
        
        Calcium ions flow out of the ER (down the concentration gradient), raising the calcium ion concertation in the cytosol.
        
        Calcium ions then activate the next protein in one or more signaling pathways.