Metabotropic transmission involves:
I. Lipophilic transmitters binding to receptors on the extracellular side of a cell membrane
II. Lipophobic transmitters binding to receptors on the extracellular side of a cell membrane
III. Lipophilic transmitters binding to receptors on the intracellular side of a cell membrane
IV. Lipophobic transmitters binding to receptors on the intracellular side of a cell membrane.
C. II & III.
D. III & IV
E. All of the above
Match the enzyme type with the description:
A. uses ATP to form a bond between substrates
B. removes the phosphate from the substrate
C. binds two substrates without using ATP
D. incorporates oxygen into substrate, mono- or di- oxygenase
E. cleaves peptide bonds by addition of water
F. interconverts isomers
G. moves group between substrates
H. transfer hydrogen from substrate to coenzyme
I. transfer phosphate from ATP to another molecule
for the Enzyme question:
1 E, 2 D, 3 F, 4 B, 5 H, 6 I, 7 A, 8 C, 9 G
metabotropic transmission = Involves stimulation of cell signaling systems via enzymes and/or genomic regulation, up and down regulation. Receptors outside the cell membrane bind lipophobic transmitters that can't cross the cell membrane because they're too polar. Lipophilic transmitters that do penetrate the membrane, such as steroids (cortisol) and thyroid hormones, bind to receptors inside the cell. More important clinically than synaptic transmission because so many drugs are designed to influence this system.
Ionotropic vs metabotropic
--Ionotropic is faster, more direct, effect doesn't last as long
--metabotropic is slower, activates a cascade of enzyems that stimulate synthesis of 2nd messengers or change gene activity, the effect lasts a while
Frst messenger is the thing that arrives and binds and starts either the ionotropic or metabotropic system. Second messengers are next step in cascade of signals in the metabotropic system.
surfing over to biochem notes--
--catalyst that lowers the transition state energy required for reaction
--subtypes: dehydrogenase, oxygenase, kinase, phosphatase, protease, trasnferase, synthase, isomerase, synthetase.
DEHYDROGENASE - transfer hydrogen from substrate to coenzyme, creates active forms of niacin and riboflavin (NAD+ and FAD+)
OXYGENASE - incorporates oxygen into substrate, mono- or di- oxygenase
KINASE - transfer phosphate from ATP to another molecule, common in 2nd messenger systems
PHOSPHATASE - removes the phosphate from the substrate, balances the kinase in 2nd messenger systems
PROTEASE - cleaves peptide bonds by addition of water (also makes peptide bonds), some proteases with "trivial names" are trypsin, chymotrypsin and pepsin, the digestive enzymes that were studied before this naming system was established.
TRANSFERASE - moves group between substrates
SYNTHASE - binds two substrates without using ATP
ISOMERASE - interconverts isomers
SYNTHETASE - a type of ligase, ATP coupled bond formation between substrates
Oxidase uses O2 but it's not incorporated into substrate carbon structure.
--cAMP and IP3/DAG are two primary examples, occur in all body cells
--cause cascade of effects in cell
--slow relative to ionotropic transmission
--metabotropic transmission using G proteins both amplifies and increases the duration of a cell's response.
--ligand binds to receptor => G protein => enzyme => 2nd messenger => effector (kinase or other enzyme) => cell function changes
-- cAMP is a second messenger, used for intracellular signal transduction (transfers effects of lipophobic hormones like glucagon and adrenaline)
--synthesized from ATP
-- activates protein kinases; it is also used to regulate the passage of Ca2+ through ion channels
--activated kinase then activates proteins by phosphorylation
--produces hours long changes in neruon excitatbility by changing permeability of nongated K+ channels
--regulates metabolic pathways incl: glucogenolysis and lipidolysis
--activates protein kinase A (PKA) which phosphorylates a transciptional activator CREB (cAMP response element binding protein) (other signaling pathways activate CREB too)
--CREB proteins are transcriptional factors (TF's) that can produce long term changes in fx of ion channels, may influence learning and conditioning.
--G protein can either stimulate or inhibit cAMP formation, total amount in cell results from balance of opposing effects
-- Inositol trisphosphate or inositol 1,4,5-trisphosphate (aka triphosphoinositol; abbreviated InsP3 or IP3), together with diacylglycerol, is a second messenger molecule
--IP3/DAG is created by hydrolysis of PIP2 (phosphatidylinositol 4,5-bisphosphate) by phopholipase C (PLC) which is activated by G protein
--PIP2 is a phospholipid found in the plasma membrane
1) mobilize Ca++ from endoplasmic reticulum for smooth muscle contraction
2) regulate cell proliferation and other cellular reactions.
--IP3 is degraded to inositol and reincorporated into the membrane, this process inhibited by lithium
--DAG (diacylglycerol) activates the enzyme protein kinase C, promotes cell division and proliferation
-- In smooth muscle cells, IP3 binds to and activates InsP3 receptor on membrane of sarcoplasmic reticulum. This opens a calcium channel, resulting in the release of Ca++ into the sarcoplasm. This increase in Ca++ activates the ryanodine receptor-operated channel on the SR, leading to a further increase in [Ca++] in muscle cell, resulting in contraction.
-- Inositol tetra-, penta-, and hexa-phosphates have been implicated in gene expression
UP and DOWN regulation
--down reg = reduction in number, activity or sensitivity of channels or receptors following continued or excess agonist action
--up reg = increase in #, activity or sensitivity of receptors or channels in response to diminished agonist action
--effects last hours to days
--mediated by changes in rate of receptor turnoriver, receptor gene transcription or receptor mRNA turnover
--important mechanisms by which regulatory systems in bod shift gears
--short for guanine nucleotide binding proteins
= a family of proteins involved in second messenger cascades
-- when the right receptor is activated it binds on the inside of the cell wall and either supplies energy or stores it via moving its 3rd phosphate group around, can generate or block 2nd messengers
-- so called because of their signaling mechanism, which uses the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP) as a general molecular "switch" function to regulate cell processes.
-- G proteins belong to the larger grouping of GTPases.
-- Gαs stimulates the production of cAMP from ATP. This is accomplished by direct stimulation of the membrane associated enzyme adenylate cyclase. cAMP acts as a second messenger which goes on to interact with and activate protein kinase A (PKA). PKA can then phosphorylate a myriad of downstream targets.
-- Gαi inhibits the production of cAMP from ATP.
-- Gαq/11 stimulates membrane bound phospholipase C which then cleaves PIP2 (a minor membrane phosphoinositol) into two second messengers, IP3 and diacylglycerol (DAG).
-- Gα12/13 are involved in Rho family GTPase signaling (through RhoGEF superfamily) and control cell cytoskeleton remodeling, thus regulating cell migration.