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Biology 225 Midterm 1


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Define Endocrine Signalling
Signal travels to distant cells via the bloodstream.
Define Paracrine Signalling
Signal travels to nearby target cells.
Define Neuronal Signalling
Signal travels between neurons (neurotransmitters released in synapse).
Define Contact-Dependent Signalling
Signalling cell and target cell are in contact; the signal molecule is bound to the membrane.
Effects of Adrenaline?
Increases blood pressure, heart rate, metabolism.
Origin: Adrenal gland.
Type: Hormone.
Nature: Tyrosine derivative.
Effects of Cortisol?
Affects metabolism of carbohydrates, proteins, and lipids in most tissues.
Origin: Adrenal gland.
Type: Hormone.
Nature: Steroid.
Effects of Estradiol?
Induces & maintains female secondary sexual characteristics.
Origin: Ovaries.
Type: Hormone.
Nature: Steroid.
Effects of Testosterone?
Induces & maintains male secondary sexual characteristics.
Origin: Testes.
Type: Hormone.
Nature: Steroid.
Effects of Glucagon?
Stimulates glycogen (& lipid) breakdown & glc synthesis (e.g. fat and liver cells).
Origin: cells of pancreas.
Type<: Hormone.
Nature: Polypeptide.
Effects of Insulin?
Stimulates glc uptake, protein & lipid synthesis (e.g. liver cells).
Origin: cells of pancreas.
Type: Hormone.
Nature: Polypeptide.
Effects of EGF?
Stimulates many cell types to proliferate.
Origin: various cells
Type: Local Mediator
Nature: polypeptide
Effects of PDGF?
Stimulates many cell types to proliferate
Origin: various cells, including platelets.
Type: Local Mediator
Nature: Polypeptide
Effects of NGF?
Promotes growth & survival of neurons
Origin: Various innervated tissues
Type: Local Mediator
Nature: Polypeptide
Effects of histamine?
Aids inflammator response by causing blood vessels to dilate and become leaky.
Origin: Mast cells
Type: Local mediator
Nature: Histidine derivative
Effects of NO?
Smooth muscle relaxation; regulates nerve cell activity.
Origin: Nerve cells; endothelia of blood vessels
Type: Local mediator
Nature: dissolved gas
Effects of Acetylcholine?
Excitatory neurotransmitter at many nerve-muscle synapses & in the CNS
Origin: Nerve terminals
Type: Neurotransmitter
Nature: Choline derivative
Effects of GABA?
Inhibitory neurotransmitter in CNS
Origin: Nerve Terminals
Type: Neurotransmitter
Nature: Glutamate derivative
Difference between hydrophillic and hydrophobic signals?
Hydrophillic signals bind to receptors at the cell's surface. Hydrophobic signals pass through the cell membrane and bind intracellular receptors.
Two major types of molecular switches?
1. Phosphorylation/dephosphorylation by kinases and phosphotases (some are on when phosphorylated, and some are off when phosphorylated)

2. GTP-binding proteins
GTP-binding proteins - when are then "On", and when are they "Off"?
They are "On" when GTP is bound, and "Off" when GDP is bound.
Give an example of how a signal molecule can induce different responses in different target cells
Acetylcholine decreases frequency of contraction in heart muscle cells; it causes contraction in skeletal muscle cells; and it causes secretion in salivary gland cells.
Explain the difference between cell-surface receptors and intracellular receptors
Cell-surface receptors are for hydrophilic signal molecules to bind to - they are on the surface of the cell, embedded in the membrade. Intracellular receptors reside inside the cell, and hydrophobic signal molecules travel right into the cell, and bind to them.
How does nitroglycerine work to relieve angina?
NO dilates the small muscles of blood vessels serving the heart, improving blood flow.
How does viagra work to relieve erectile dysfunction?
It inhibits the breakdown of cGMP by cGMP phosphodiesterase
What are GAPS and how do they work?
GTPase activating proteins. They accelerate G protein's intrinsic GTPase activity (they are an accessory protein, which aid cycling between active and inactive states of a G-protein switch by binding to the G-protein)
What are GEFs and how do they work?
Guanine nucleotide-exchange factors. They bind inactive G proteins and stimulate exchange reaction.
(they are an accessory protein, which aid cycling between active and inactive states of a G-protein switch by binding to the G-protein)
What are GDIs and how do they work?
Guanine nucleotide-dissociation inhibitors. They inhibit release of bound GDP thus maintaining the protein in its inactive state.
(again, part of the g-protein switch)
Three ways that a signal can affect a cell?
1. Altered protein function
2. Altered gene expression
3. Altered cytoplasmic machinery
Name three types of cell surface receptors for hydrophilic signalling molecules.
G-protein-coupled receptors (GPCRs); Enzyme-linked receptors; Ion-channel-linked receptors.
How do GPCRs work?
Cytosolic domain binds heterotrimeric G-proteins.
How do enzyme-linked receptors work?
Cytosolic domain either acts as an enzyme (eg RTKs), or complexes with an enzyme. Most dimerize upon binding ligand. Primarily, they regulate growth, survival, and differentiation.
How do ion-channel-linked receptors work?
e.g. the nicotinic Ach receptor
What is the most frequent effector targeted by heterotrimeric G-proteins?
adenylate cyclase; phospholipase c (PLC) is also a major target
What does cAMP usually do?
activates PKA (protein kinase A)
Give some examples of induced calcium release
cardiac muscle, skeletal muscle
What is CREB?
(Cyclic-AMP Response Element Binding) proteins are transcription factors which bind to certain sequences called CRE elements in DNA and thereby increase or decrease the transcription of certain genes.
What is calmodulin?
Calmodulin (CaM) is a Ca2+-binding protein that is a key component of the Ca2+ second-messenger system and is involved in the modulation of protein kinases and other enzymes.
What is the role of calcium in cell signalling?
A second messenger.
How many calcium binding sites does calmodulin have?
4 Ca2+ binding sites.
What is Troponin C?
A protein - modulator of muscle contraction.
What is Calretinin, retinin?
A protein - activator of guanylyl cyclase.
What is PI-specific PLC?
A protein - generates IP3 and diacylglycerol.
What is PKC?
A protein kinase.
What is an IP3 receptor?
Effector of intracellular Ca2+ release.
What is arrestin?
Terminator of photoreceptor response.
How does cholera toxin (cholera) modify G-proteins?
It catalyzes ADP ribosylation of Gs... can no longer hydrolyze bound GTP, so permanently on.
How does pertussis toxin (whooping cough) modify G-proteins.
It catalyzes ADP ribosylation of Gi... cannot interact with receptors. Retains GDP, so permanently off. Also interferes with signally pathway that the host cells require to defend themselves against the pathogen.
What are phorbol esters?
Tumour promotes that imidiate DAG - activate PKC
What are oncogenes?
Mutated receptor genes or mutated genes, encoding components of Ip3/DAG pathway.
What is DAG?
Diacylglycerol (DAG) is a second messenger molecule made by phospholipase C (a membrane-bound enzyme), together with inositol triphosphate. Although inositol triphosphate diffuses into the cytosol, diacylglycerol stays close to the plasma membrane, due to its hydrophobic properties.
Difference between PKA & PKC, and RTKs
PKA & PKC are serine & threonin kinases that primarily regulate intermediate metabolism. RTKs are tyrosine kinases that primarily regulate cell growth, survival, and differentiation.
What are RTKs?
Receptor tyrosine kinases. Most are monomeric, bitopic transmembrane proteins. Most dimerize after binding ligands.
Examples of RTKs
EGF, PDGF, NGF, insulin
What is Ras?
A small monomeric g-protein. Hydrolyzes GTP. Inactive form has GDP-bound; active form has GTP-bound. Has very weak intrinsic GTPase activity. Member of several signalling pathways. Important in cancer! (ras oncogenes are known to occur in ~30% of all human tumours).
What makes cAMP?
Adenylyl cyclase
What does cAMP usually bind to?
PKA (Protein kinase A) - it binds to inhibitory subunits, allowing the catalytic subunits to be active.
What does phosphorylation of glycogen synthase do?
Inhibits conversion of glucose to glycogen.
What does PKA do?
Mobilizes glucose.
How does PKA mobilize glucose?
Phosphorylation of glycogen synthase, and phosphorylation of phosphorylase kinase.
What does phosphorylase kinase do?
Activates the enzyme to catalyze the transfer of phosphate groups to glycogen phosphorylase molecules (speeding up glycogen phosphorylase).
Nonpolar molecules - regulate a variety of processes including pain, inflammation, blood pressure, and blood clotting. Several over-the-counter drugs that are used to treat headaches and inflammation inhibit eicosanoids.
How many transmembrane alpha helices do GPCRs contain?
What do RTKs usually do?
Receptors - typically involved in the regulation of cell division and differentiation.
What do ligand-gated channels usually function as?
Receptors for neurotransmitters.
Troponin C?
Modulator of muscle contraction (activated by Ca2+)
IP3 receptor?
Effector of intracellular Ca2+ release.
Ryanodine receptor?
Effector of intracellular Ca2+ release.

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