12 Biochemical signaling Flashcards
Common Attributes of Signal Transduction Systems
Specificity: complementarity between signal and receptor.
Sensitivity: high affinity of signal receptors for ligand/signal molecule.
Amplification: Enzyme cascades, receptor activates several enzymes, which activates several enzymes etc.
Modularity: Proteins with several domains for different structures, allowing for a variety of multienzyme complexes.
Deactivation/desensitization: continous signaling makes receptor desensitized/less sensitive.
Integration: several signals to receptor are integrated into one response.
Divergence: One signal may activate more than one pathway.
Localized response: Components of signal system are confined to a space in the cell, local regulation of a process.
What Is The General Process of Signal Transduction?
Signal binds to receptor. Receptor is activated and produces second messengers, or changes activity of cellular proteins and changes metabolism. Termination of transduction event.
What Are The Four General Types of Signal Transduction?
1: G protein-coupled receptor (GPCR).
2: Receptor enzyme/tyrosine kinase.
3: Gated ion channel.
4: Nuclear receptor.
What Is The General Mechanism of G Protein-Coupled Proteins?
Ligand binds to receptor and activates an intracellular G protein (GTP binding protein). The protein regulates/activates an enzyme that produces a second messenger.
What Is The General Mechanism of Tyrosine Kinases?
Ligand binding to the tyrosine kinase activates the enzyme by autophosphorylation. A kinase cascade produces a transcription factor that changes gene expression.
What Is The General Mechanism of Gated Ion Channels?
Concentration of signal opens the channel and allows for the passing of ions to the cytosol.
What Is The General Mechanism of Nuclear Receptors?
Hormone may pass straight through the plasma membrane into the nucleus to bind to a receptor that regulate the expression of specific genes.
Explain The Process of Epinephrine Binding To GPCR To The Release of Second Messenger and Deactivation Including Names and Subunits of Enzymes
Binding of epinephrine to beta-adrenergic receptor leads to allosteric changes and the substitution of GDP with GTP. The activated Gs has three subunits alpha(a), gamma (y) and beta (b). y- and b-subunits dissociates from to a yb dimer and a Gsa subunit. Gsa-GTP moves to nearby adenyl cyclase, which is activated to catalyze formation of cAMP from ATP. GTP of Gsa is hydrolyzed to GDP by integral GTPase, reunited with the yb-dimer, and forms an Gs.
Shortly Explain The Structure of cAMP-Dependent Protein Kinase (PKA) and Its Activation by cAMP
PKA consists of two regulatory and two catalytic subunits (R2C2 complex). Binding of cAMP allosterically activates the complex to free the catalytic subunits and allow catalytic activity.
Briefly Explain the Amplification of the Adrenaline Cascade (GCPR to Released Glucose) With the Involved Enzymes
Epinephrine binding to Gs activates adenyl cyclase releasing cAMP. cAMP activates PKA which activates phosphorylase b kinase. This activates glycogen phosphorylase b which in turn activates glycogen phosphorlyase a. Glycogen is then degraded to glucose 1-phosphate and glucose.
Name Some Mechanisms for Terminating the b-Adrenergic Response
1: Desenzitation of the receptor.
2: GTPase activator proteins (GAPs) activates GTPase which deactivates Gs.
3: cAMP (second messenger) is deactivated by hydrolyzation by cyclic nucleotide phosphodiesterase (CNP?).
4: The effects of PKA (phosphorylation) is reversed by phosphoprotein phosphatases (hydrolyzation/removal of phosphate groups).
5: Blood concentration of the ligand (epinephrine) falls.
What Is The Function of b-Arrestin?
b-Arr binds to the receptor and blocks the binding sites of epinephrine, therefore desensitizing the receptor to the ligand. This occurs after phosphorylation of the receptor by b-Adrenergic Receptor Kinase (bARK).
Mention Other Second Messengers Apart From cAMP and The Mechanisms Leading To Their Release
Diacylglycerol (DAG) and insonitol triphosphate (IP3).
These second messengers are released by cleavage of membrane phospholipid PIP2, a reaction catalyced by phospholipase C (PLC). The enzyme is activated by a type of G-protein, Gq.
What Are The Results of DAG and IP3 In The Cell?
IP3 binds to an IP3-activated ion channel in the ER, opening it and releasing Ca2+ into the cytosol. The Ca2+, helped by DAG, activates protein kinase C (PKC) which can phosphorylate proteins.
Explain The General Mechanism And Structure of Tyrosine Kinases
Tyrosine kinase consists of two extracellular a-units, and two transmembrane b-units. On ligand binding (f.eks insulin). a-units contain ligand binding site, and b-units contain protein kinases. Ligand binding moves b-units (and tyrosin kinase domains) together. The b-units phosphorylates eachother (autophosphorylation). The active site is now open and can phosphorylate tyr-residues of other proteins. This activates a phosphorylation cascade of different proteins and ultimately results in changes in gene transcription.
