Basic Science block I

Choline Acetyltransferase

Ach Transferase

Glutataminase

Glutamine synthetase (in Glial Cells)

Glutamic acid decarboxylase

Mitochondria

in the NUCLEUS

along MICROTUBULE tracks

Proteolytic enzymes

• 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

• 1. diffusion away from the site of action
• 2. re-uptake into cells
• 3. enzymatic cleavage

Ligands coming from the outside environment, ie. outside the body

Ligands that are made in the body and are packaged and released locally.

All proteins begin production at the nucleus

• 1. the distance the ligand must travel to the receptor
• 2. What kind of receptor it binds to

• 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

Different target cells express different receptors and different secondary messengers.

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.

• 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.

• 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.

It is a Dimer protein receptor that can act as Insulin receptor, Epidermal Growth Factor (EGF), and Platelet derived growth factor (PDGF)

• Tyrosine Kinase
• Guanalyl cyclase

receptors within the cytoplasm: requires ligands to access their receptors intracellularly. Such examples include: Cortisol, Estradiol, Testosterone, Vitamin D3 (basically nonpolar hormones)

fast onset, short duration, open ion-selective pore through membrane

Slower onset, signal is amplified, activate ion channels OR diffusible to 2nd messengers

slower onset, activation of multiple different cascades-->amplification, longer duration,

an atrial natriuretic factor, vascular tone

Transforms growth factor-beta,

• 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.

• 1. Adenyly cyclase
• 2. Protein kinase
• 3. Protein phosphatase
• 4. Guanyly cyclase
• 5. Phspholipase C (PLC)
• 6. Calcium

• 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

• 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)

removes a 2 phosphatea from ATP-->cAMP

Degrades cAMP-->AMP by forming an ester bond

• 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

Phosphodiesterase

PLC is activated by G-Proteins (G-alpha-q and/or G-beta-gama), cleaves PIP2-->DAG and IP3

• -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

a common protein phosphatase