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Acetyl coA + Choline --?--> Ach
Ach --?-> Acetate + Choline
GlutaMINE --?--> GlutaMATE
Glutamine synthetase (in Glial Cells)
Glutamate --?--> GABA
Glutamic acid decarboxylase
Synthesis of neurotransmitter precursors and enzymes are made where?
in the NUCLEUS
Transportation of enzymes nad pre-peptide precursors occur where?
along MICROTUBULE tracks
What generally degrades Neurotransmitters?
Name the 4 types of chemical signalling and explain their function
- 1. Autocrine-self activation
- 2. Paracrine-ligands diffuse to neighboring cells
- 3. Synaptic- more cell specific by localization of ligands within synaptic terminals
- 4. Endocrine: Systematic diffusion into the blood stream with slow onset and prolonged action
Generally they differ in speed of actions and variable selectivity
What stops the action of ligands?
- 1. diffusion away from the site of action
- 2. re-uptake into cells
- 3. enzymatic cleavage
what are exogenous ligands?
Ligands coming from the outside environment, ie. outside the body
what are endogenous ligands?
Ligands that are made in the body and are packaged and released locally.
Where are proteins made?
All proteins begin production at the nucleus
What determines the speed of onset of a ligand-receptor binding?
- 1. the distance the ligand must travel to the receptor
- 2. What kind of receptor it binds to
what determines the duration of enzyme-ligand action?
- 1. diffusion from the site of ligand release
- 2. whether it gets taken up by their own cell or another cell
- 3. whether it is cleaved by an enzyme
explain how one ligand can cause different effects upon binding to receptors on different cells?
Different target cells express different receptors and different secondary messengers.
Explain the general mechanism of ligand-gated ion channels esp. for Ach
Ach ligand binds to a 5 transmembrane subunit receptor (barrel shaped) and causes a conformational change to open the ion channel. In this case, 2 Ach is required to initiate action. Once channel is opened, semi specific ions are free to flow down their concentration gradient.
Explain the mechanism of G-Protein Coupled receptor
- G protein coupled receptor uses its G-protein as a secondary messenger
- 1. Ligand binding to a 7-transmembrane G-protein coupled receptor on the outside of the membrane.
- 2. GTP displaces GDP on the G-protein subunit and the entire complex disocciates.
- 4. G-alpha or G-beta activates an effector protein or ion channel
- 5. Phosporylase removes phosphate group from GTP --> GDP deactivating the Gprotein subunit.
- 6. Gprotein subunits reattaches to each other and to the transmembrane subunits.
Explain the mechanism of Enzyme-linked Receptors
- Enzyme-linked receptor uses an enzyme as its secondary messenger: in this case Tyrosine Kinase receptor uses its own Tyrosine Kinase as a secondary messenger
- 1. Ligand binding cause conformational change causing the duo tyrosine kinases to join
- 2. The tails of the polypeptides phosporylates each other (self phosphorylates)
- 3. Phosphorylated tyrosine kinase is recognized by different relay proteins and initiate several effects.
What is Tyrosine Kinase?
It is a Dimer protein receptor that can act as Insulin receptor, Epidermal Growth Factor (EGF), and Platelet derived growth factor (PDGF)
Name two enzyme-linked receptors that acts as growth factors
- Tyrosine Kinase
- Guanalyl cyclase
What are Intracellular receptors?
receptors within the cytoplasm: requires ligands to access their receptors intracellularly. Such examples include: Cortisol, Estradiol, Testosterone, Vitamin D3 (basically nonpolar hormones)
describe the characteristics of Ligand gaed ion channels.
fast onset, short duration, open ion-selective pore through membrane
Describe the characteristics for G-protein linked couple receptors.
Slower onset, signal is amplified, activate ion channels OR diffusible to 2nd messengers
Describe the characteristics of enzyme-linked receptors.
slower onset, activation of multiple different cascades-->amplification, longer duration,
What is Guanylyl cyclase?
an atrial natriuretic factor, vascular tone
What is serine kinase?
Transforms growth factor-beta,
name 3 types of cell surface receptors and their relative mechanism
- 1. Ligand-gated ion channels: Ionotropic and fast acting
- 2. G-protein linked receptors: Metabotropic, long duration, activates 2nd. messengers
- 3. Enzyme linked receptors: have integral enzymatic sites.
Name the 2nd messengers learned in class
- 1. Adenyly cyclase
- 2. Protein kinase
- 3. Protein phosphatase
- 4. Guanyly cyclase
- 5. Phspholipase C (PLC)
- 6. Calcium
What are 2nd messengers?
- 1.They are molecules that are produced/activated upon recport binding that diffuses within the cell (memb or cytoplasm).
- 2. Amplifies original signal and may act upon several effector molecules
Explain how Protein Kinase A (PKA) act.
- 1. PKA is a secondary messenger that is activated by cAMP to phosphorylate its substrates
- 2. Activity in the cytoplasm: act as an enzyme in glycogen metabolism
- 3. Activity in nucleus: stimulates transcription via CREB (cAMP Responsive Element Binding Protein)
Activity of Adenyly Cyclase
removes a 2 phosphatea from ATP-->cAMP
Degrades cAMP-->AMP by forming an ester bond
name the several Protein Phosphatases and their action
- 1. Protein phosphatase I: reverses phosphorylation done by PKA (ex: CREB)
- 2. Protein Phosphatase IIA: Reverses phosphorylation done by serine/threonin kinases
- 3. Protein Phosphatase IIB: (calcineurin): activated by Ca2+ and is abudant in neurons
- activated via Enzyme linked receptor, dephosphorylates GTP-->cGMP (cyclic Guanosine Phosphate) which acts as a 2nd messenger to
- 1. activate cGMP dependent protein kinase ex. PKG
- 2. common regulator of ion channel conductance, glycogenolysis, cellular apoptosis, relaxes SM tissues such as Blood Vessels
What degrades cGMP-->GMP
PLC is activated by G-Proteins (G-alpha-q and/or G-beta-gama), cleaves PIP2-->DAG and IP3
Characteristics of Ca2+
- -an Ubiquitous INTRACELLULAR signal.
- -enters thru selective Ca2+ ion channels
- -its concentration is tightly regulated at 10^-4 via pumps
- -required for action potential mediated release of synaptic vessicles
- -activates other ion channels
- -binds calmodulin
what is calmodulin?
a common protein phosphatase