Lectures 5 & 6 JUST Terms Flashcards
Adenylyl Cyclase
membrane-bound enzyme that converts ATP to cyclic AMP
Afferent Pathway
the pathway that connects a receptor to an integrating center
Agonists
molecules that combine with a receptor & mimic a response
Amplifier Enzyme
a membrane enzyme that creates 2 or more 2nd messengers during signal transduction
Antagonists
1 substance opposes the action of another
Arachidonic Acid
20-carbon fatty acid precursor of eicosanoid signal molecule
dual function:
- are themselves 2nd messengers within a cell
- diffuse out of the cell & act as a ligand for GPCR cell membrane & adjacent cells
Autocrine Signal
signaling to self
Calmodulin
intracellular 2nd messenger that binds Ca2+
- a calcium-binding protein which then activates other proteins
Cascade
response in which a series of inactive molecules convert to active forms until a product is formed
Cellular Response
the end of the line for a signal brought to the target cell by a signaling molecule ?
Chemical Signals
are molecules secreted by cells into the ECF
Connexins
each connexon is made of 6 connexin monomers/subunits
2 connexons (12 connexins) form a functional gap junction b/t 2 adjacent cells
Contact-Dependent Signals
a molecule (ligand) in the extracellular matrix of one cell binds to a receptor in the membrane of the adjacent cell - immune system, development
Cyclic AMP (cAMP)
- a second messenger molecule synthesized by adenylyl cyclase
- cAMP is a small molecule that diffuses throughout the cell, & activates the PK-A protein kinase
- some GPCR pathways activate adenylyl cyclase, some inhibit it (allowing the concentration of cAMP in a cell to decrease)
Cytosolic Receptors (nuclear receptors)
the binding sites for steroid hormones, thyroid hormones, vitamin D, and retinoic acids. ?
Dephosphorylation
removal of a phosphate group
Desensitization
reversible form of receptor down-regulation achieved using modulators
- receptors can be desensitized - meaning they need higher dose to achieve the same effect
Diacylglycerol (DAG)
a lipid product of the cleavage of phospholipid in the cell membrane by the enzyme PL-C
- this lipid remains associated with the cell membrane, & can achieve the PK-C enzyme
Drug Tolerance
down-regulation & desensitization are 1 explanation for the development of drug tolerance, a condition in which the response to a given dose decreases despite continuous exposure to the drug
Effectors
the cell or tissue that carries out the homeostatic response
Efferent Pathway
outgoing signal that goes from the integrating center to an effector
Eicosanoids
are a subset of oxylipins
- polyunsaturated fatty acid, having a length of 20 carbon atoms
Arachidonic Acid is an ex
Electrical Signals
are changes in the cell’s membrane potential
- when the ligand binds, the channel opens. allows ions to enter & leave cells
Feedback Loop
modulate the response loop
Feedforward Control
allows the body to ANTICIPATE change, generate a response before variable changes (may be argued this is not a loop)
First Messenger
chemical signal molecules released by cells
G Protein
membrane proteins that couple membrane receptors to ion channels or membrane enzymes
- called g-proteins b/c they bind GDP & GTP
G Protein-Coupled Adenylyl Cyclase-cAMP system
the first signal transduction system discovered
G Protein-Coupled Receptors (GPCR)
hundreds of known GPCR
- many have unknown functions (orphan receptors)
also called
- metabotropic receptors
- 7 transmembrane domain receptor (7TR)
- serpentine receptor
activation of GPCR leads to generation/release of second messengers
Gap Junctions
- Channels that connect adjacent cells
- 2 adjacent cells express channel proteins called connexins - Water filled pore: allows small molecules & ions to diffuse from one cell to the next
- Common in heart, smooth muscle, & some neurons
- Cells are connected by cytoplasmic bridges
Guanylyl Cyclase
enzyme that controls formation of cyclic GMP
- which leads to relaxation of smooth muscle
Histamine
paracrine secreted by mast cells & basophiles; acts as a vasodilator & bronchoconstrictor ?
Hormones
chemical secreted by a cell or group of cells into the blood for transport to a distant target where it acts in very low concentrations to affect growth, development, homeostasis, or metabolism
Inositol Triphosphate (IP3)
- a second messenger molecule produced by the hydrolysis of phospholipids in the cell membrane by PL-C
- IP3 is small & water soluble, & diffuses easily throughout the cell, but not across cell membranes
- IP3 binds to the IP3 receptor channel located in the endoplasmic reticulum of the cell
- this causes the IP3 receptor channel to gate open, & release sequestered Ca2+ into the cytoplasm, thus causing a large increase in free intracellular Ca2+
- when the IP3 receptor channel gates closed, Ca2+ ATPase transporters pump the cytoplasmic Ca2+ back into the endoplasmic reticulum stores
Integrating Center
the control center that evaluates incoming signal & decides on an appropriate response
Integrin Recptors
- binds extracellular matrix proteins (collagen for ex)
- binding ligand stimulates changes in cytoskeleton
- which then causes: cell movement, growth, wound healing
Ligand
the molecule that binds to a protein
Ligand-Gated
aka receptor channel (ion channel)
- the ligand is often a neurotransmitter
- when the ligand binds, the channel opens
- allows ions to enter & leave cells = electrical signal (synaptic transmission)
- allow Ca2+ into cells (calcium is an important intracellular signal)
Lipophilic Signal Molecules
enter cells by simple diffusion through the phospholipid bilayer of the cell membrane
Lipophobic Signal Molecules
are unable to enter cells by simple diffusion through the cell membrane
- instead, these signal molecules remain in the extracellular fluid & bind to receptor proteins on the cell membrane
Local Communication
includes
(1) GAP JUNCTIONS, which allow direct cytoplasmic transfer of electrical & chemical signals b/t adjacent cells
(2) CONTACT-DEPENDENT SIGNALS, which occur when surface molecules on another cell’s membrane; &
(3) chemicals that diffuse through the ECF to act on cells close by
Long-Distance Communication
(4) uses a combination of chemical & electrical signals carried by nerve cells & chemical signals transported in the blood
Negative Feedback
are homeostatic - stabilize variable
Neurocrine
any molecule secreted by a nerve cell
Neurohormone
an electrical signal travels distance along a nerve cell
- causes release of a chemical
- the chemical is released into the blood, & acts at DISTANT targets
Neurotransmitter
an electrical signal travels distance along a nerve cell
- causes release of a chemical
- the chemical travels ACROSS A SMALL GAP ONTO A TARGET
Output Signal
part of control system ?
Oxytocin
posterior pituitary hormone that causes uterine & breast smooth muscle constraction
Paracrine Signal
signaling to cells in the immediate vicinity
Phospholipase A2 (PLA2)
enzyme that converts a membrane phospholipid into 2 different 2nd messenger molecules, DAG & IP3
Phospholipase C (PL-C)
an amplifier enzyme that primarily converts membrane phospholipids (primarily Phosphatidylinositol 4,5-biphosphate) into the messengers:
(1) Diacylglycerol &
(2) Inositol tri-phosphate
Physiological Control System
can operate over short or long distances
- local = cells & tissue level
- long distance = endocrine or nervous control (“reflex control”)
Positive Feedback Loop
reinforce a stimulus
- are NOT homeostatic? (some people think this)
Protein Kinase A (PK-A)
- cAMP activates protein kinase A (PKA)
- PKA diffuses within cell to phosphorylate many other proteins
- many types of proteins can be phosphorylated, giving rise to complex/co-ordinated cellular responses
Protein Kinases
enzymes that transfer a phosphate group from ATP to a protein
Protein Phosphates
a phosphatase enzyme that removes a phosphate group from the phosphorylated amino acid residue of its substrate protein ?
Receptor
a cellular protein that binds to a ligand
Receptor-Channel
(ion channel)
- the ligand is often a neurotransmitter
- when the ligand binds, the channel opens
- allows ions to enter & leave cells = electrical signal (synaptic transmission)
- allow Ca2+ into cells (calcium is an important intracellular signal)
Receptor-Enzymes
membrane proteins that bind ligands on the extracellular side & activate enzymes on the intracellular side
Response Loop
control pathway that begins with the stimulus & ends with the response
Second Messenger System
intracellular molecules that translate the signal from a 1st messenger into an intracellular response
Second Messengers
is a signaling molecule synthesized or released by a cell in response to an extracellular signalling molecule (hormone, for ex)
- sometimes they are synthesized, sometimes they are released from a storage compartment
Sensitivity
the ability of an organism or organ to respond to external stimuli. ?
Setpoint
the physiological value around which the normal range fluctuates ?
Signal Amplification
a small amount of ligand creates a large effect
- aka the generation of a large # of intracellular molecules
Signal Transduction
is the process by which an extracellular signal molecule activates a membrane receptor that in turn alters intracellular molecules to create a response
- converts one form of signal to another
Specificity
the ability of an enzyme or receptor to bind to a particular molecule or a group of closely related molecules
Syncytium
when the channel is open, the connected cells function like a single cell that contains multiple nuclei (syncytium) ?
Target Cells (Targets)
A target cell responds to a hormone because it bears receptors for the hormone. In other words, a particular cell is a target cell for a hormone if it contains functional receptors for that hormone, and cells which do not have such a receptor cannot be influenced directly by that hormone. ?
Transducer
is a device that converts a signal from one form into a different form
Tyrosine Kinase
transfers a phosphate group from ATP to a tyrosine residue (an amino acid) of a protein, enhancing or inhibiting its activity. (phosphorylates tyrosine residues)
Amplification Signal
a small amount of ligand creates a large effect
- aka the generation of a large # of intracellular molecules ?
Catalytic Receptor
2 types:
- receptor-enzyme: ligand binding to a receptor-enzyme activates an intracellular enzyme
- integrin receptor: ligand binding to integrin receptors alters enzymes of the cytoskeleton
Central Receptor
sensory receptors located in or closely linked to the brain
Cycloxygenase (COX)
enzyme that converts arachidonic acid to prostanoids
Cytokinases
physical process of cell division ??
Endogenous
an endogenous ligand is something natural in your body: for ex a hormone or neurotransmitter
non-endogenous may be a drug or toxin
Epinephrine (Adrenaline)
activates alpha & beta2 receptors
Half-Life
the amount of time required to reduce the concentration of hormone by one-half
Hydrogen Sulfide
a soluble gas recognized as second messengers
- the newest gaseous signal molecule to be described
- also acts in the cardiovascular system to relax blood vessels
Leukotrienes
are molecules produced by the action of the enzyme lipoxygenase on arachidonic acid
- are secreted by certain types of white blood cells
- they play a significant role in asthma, a lung condition in which the smooth muscle of the airways constrict, making it difficult to breathe, & in the severe allergic reaction known as anaphylaxis
- for this reason, pharmaceutical companies have developed drugs to block leukotriene synthesis or action
Input Signal
when activated by a change, the sensor sends an input (afferent) signal to the integrating center for the reflex
Janus Kinase (JAK)
is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. ?
Neuromodulator
chemicals that alter the response of a neuron more slowly than neurotransmitters
Orphan Receptors
one that has no known ligand (AKA unknown function)
Peripheral Receptors
sensory receptors that are not located in or close to the brain
Prostaglandins
part of the arachidonic acid cascade
- prostanoids are molecules produced when the enzyme cyclooxygenase (COX) acts on arachidonic acid
- prostanoids include prostaglandins & thromboxanes
- these eicosanoids act on many tissues of the body, including smooth muscle in various organs, platelets, kidney, & bone
- in addition, prostaglandins are involved in sleep, inflammation, pain & fever
Protein-Coupled Receptor
g-protein-coupled receptors (GPCRs) are a large & complex family of membrane-spanning proteins that cross the phospholipid bilayer 7 times
Reflex
any long-distance pathway that receives input about a change, integrates the information, & uses the nervous system, endocrine system, or both to react appropriately
Pathways
network of interconnected chemical reactions formed by the enzymatic reactions of metabolism
Sensor
or sensory receptor continuously monitors its environment for a particular variable
Stimulus
the disturbance or change that sets a reflex in motion
Systemic Response
describes what those specific cellular & tissue events mean to the organism as a whole
- ex: when the blood vessels constrict, the systemic response is an increase in blood pressure
Threshold
(1) the minimum depolarization that will initiate an action potential in the trigger zone
(2) the minimum stimulus required to set a reflex response in motion
Thromboxanes
part of the arachidonic acid cascade
- prostanoids are molecules produced when the enzyme cyclooxygenase (COX) acts on arachidonic acid
- prostanoids include prostaglandins & thromboxanes
- these eicosanoids act on many tissues of the body, including smooth muscle in various organs, platelets, kidney, & bone
Tonic Control
ongoing control that is adjusted up & down
Transduce
Transduction is the process by which a virus transfers genetic material from one bacterium to another ?