Biochem lecture 18/19

Receptor location/response speed and what it changes

On cell surface, cytoplasm or nucleusResponse speed can be fast or slowFast- milliseconds to minutes — protein functionSlow- minutes to hours — transcription and protein synthesis


A molecule that binds specifically to a receptor site of another molecule.


a molecule that, by binding to a receptor site, stimulates a response


A ligand that causes the receptor to become inactive

Opiods action on cells

Agonists - heroid, morphine, fentanyl are all agonists for the u-receptor endogenous ligant beta endorphin, endomorphine 1.2

Beta blockers action on cells

Inhibitors of the beta adreneric receptors such as proponol and atenololEndogenous ligands are adrenaline/epinephrine and noradrenaline/norepinephrine

Endogenous ligands

neurotransmitters or hormones made inside the body

Membrane bound receptors

Embedded in the membrane with ligand binding site to the extracellular spaceBinding of ligand on outside activates the receptor which sends signal to the inside of the cell

Intracellular receptors

Hydrophobic ligands can transverse the plasma membrane and bind receptors inside the cell

Cytoplasmic receptors

Binds ligands in cytoplasm, becomes activated, then moves into nucleus to regulate gene transcription

Nuclear receptors

Ligand enters the nucleus to bind its receptor, activates it, then bind DNA and promote transcription of target genes

Ligand-gated ion channel receptor

Involved in rapid synaptic signaling between electrically excitable cellsTransduce chemical into electrical signalsRapid responseImportant for electrically excitable cells (nerves and muscles)

G protein coupled receptors - structure, position of amino/carboxyl terminals, regulation, ex of medication that blocks them

7 pass transmembrane protein, indirectly regulate the activity of a target protein through trimeric GTP binding protein (G-protein)Amino group is exposed to outsideCarboxyl is exposed to the inside of the cellBeta blockers

Enzyme linked receptors

Single pass transmembrane proteinFunction directly as enzyme or directly associated with enzymes the activate

Ligand gated ion channels sequence of events

1. Before binding ligand- closed2. Ligand bind3. Channel conformation change- ions pass and induce cellular response4. Ligand dissociates5. Protein closed

action potential propagation

1. Action potential at presynaptic axon2. Vesicle loaded w/ neurotransmitter fuse w/ presynaptic membrane releasing ligand3. Ligand binds to ligand-binding site at the post-synaptic membrane channel, opening the channel4. When enough ions pass through it alters the voltage at the membrane —> triggering voltage gated channels to respond propagating the signal

Excitatory ligand gated ion channels

Promoting (depolarize)Na+ channels —> allows positive ions to flow into the cell depolarizing the membrane

Inhibitory ligand gated ion channels

HyperpolarizingCl channels —> allows negative ions to flow into cell, hyperpolarizingK —> allows positive ions to flow out of the cell, hyperpolarizing

Cholinergic receptors- what do they bind, where are they found, names

bind to Ach, located in CNS and PNS, nicotinic and muscarinic

Nicotinic receptors- what are they made of, what acts on them, 2 subtypes

Receptor is made of 5 subunits arranged symmetrically around a central pore2 subtypes1. Neuronal type - nicotinic receptors Nn found in both CNS and PNS located before or up stream from other types of receptorsMuscle type- nicotinic receptors Nm post synaptically on neuromuscular junctions responsible for skeletal muscle contractions

Muscarinic receptors - what do they respond to, what do they use to propagate signal, subtypes?

Respond to Ach and muscarine Metabolic receptors/G protein coupled - use 2nd messenger signal to propagate signal5 subtypesM1- Gq protein-coupled increases exocrine gland secretions, CNSM2 Gi protein coupled increase heart parasymptathetic effectsM3 Gq protein coupled increase parasymp effects (bronchoconstriction, endocrine/exocrine gland secretion, eye accommodation, vasodilation)

[...] neurons release Ach that binds to [...] receptors in the [...]. These neurons then release [...] that go on to bind [...] at taget tissues

pre ganglionic neuronsNicotinicPost ganglionic neurons on target cellsCatecholamines (adrenaline and noradrenaline)Andreneric receptors

What release Ach when it binds to muscarinic receptors on target cells?

Post ganglionic neurons

When is ACh released into the synaptic cleft?

Following an action potential

What does Ach binding to nicotinic receptors trigger? How does Ach bind? Is it excitatory or inhibitory?

Muscle contraction2 Achs bind to the alpha subunits induces small rotations of the five subunits - opening the channelExcitatory ligand gated ion channels allowing Na+ flow into the cell and K+ flow out of the cell —> depolarization

Nicotinic receptor antagonists

Essential contributors to neuronal excitability, making them the most commonly target ion channel family by toxins found in animal venoms (insects, plants)Blocks action of Ach — paralysis and deathCurareCobra toxinFugu (tetrodotoxin and saxitotoxin)

How do G protein-coupled receptors work? Subunits? Inactive versus active state?

3 subunits- alpha and beta [interact w/ receptor], gamma They act indirectly on a second protein (enzyme or channel)GTP bound to alpha- active —> alpha uses GTP energy, leaving GDP — inactive beta gamma (we have 700 in body)

Three major families of trimeric G proteins


Protein Kinase A catalytic subunit

Phosphorylates other proteins to trigger cellular response

IP3 activates


DAG activates

protein kinase C

Beta 2 andrenergic receptor agonists

Widely used for treatment of asthma because of their bronchodilator effects

Histamine stimulation of H1 GPCRs constricts

Airway smooth muscle —> asthma

Receptor regulation

Receptor desensitization- Occurs via phosphorylationEndocytosis- decrease cell surface, internalizationDegradation- down regulation

heterologous regulation

The hormone regulates number and/or affinity of another hormone's receptor

Protease-activated receptors (PARs)

G-protein receptors which mediate thrombin activation of cells

Receptor tyrosin kinases

58 in bodyLigand binds- dimerize- phosphorylates itself on tyrosine residues Life maintaining pathway—> insulin

JAK-STAT pathway

A signal transduction pathway that transfers the signal directly from the cell surface receptor to the nucleus. It is usually activated by cytokines that bind receptors associated with tyrosine kinases (referred to as JAKs). On receptor dimerization, JAKs phosphorylate themselves, the receptors, and another set of proteins called STATs, which then dimerize and translocate to the nucleus where they induce the expression of a series of genes.

Modes for endogenous signaling-

Classify by distance

4 main stages of cellular communication cascade

1. Secretion of the signal2. Reception —> molecule binds to its receptor3. Signal transduction —> receptor senses the interaction with the ligand and changes conformation —> activates intracellular messengers (second msgn)4. Cell response

3 types of G- proteins

Gs, Gi, Gq; each have different effects which the ligand binds to the GPCR otuside the cell

Second messengers are important for [...]

Signal amplification

Gq activation

Phospholipase C —> PLC cleaves phosphatidylinositol 4,5 bp, a lipid at the cell membrane, yielding inositol triphosphate and DAG

DAG interacts and activates



inhibits adenylate cyclase, which decreases levels of cAMP in the cell

Cascade effect

One signal gets amplified and affects many molecules downstream

How does coffee affect the cell?

CAMPs get inactivated by phosphodiesteraseCoffee inhibits phosphodiesterageProlonged breakdown of glycogenSmall boost to blood glucose

Activation of M3 muscarinic receptor

Increase in intracellular calcium

Activation of beta 2 andreneric receptor

Releases smooth muscle contraction

Blocking H1 receptor

Release smooth muscle contraction

Intrinsic kinase activity

Receptors consist of extracellular ligand binding domain, transmembrane domain, intracellular kinase domain

2 types of receptors directly related to kinase activity

1. Receptors w/ intrinsic kinase activity2. Receptors w/ associated kinase activity;

Receptor tyrosine kinases are highly active during

Embryonic development, organogenesis, tissue patterning, body plan formation

What do RTKs signal in response to?

Ligands (growth factors, cytokines, hormones) Several ligands can activate 1 RTK

Ras can activate

MAP kinases

3 groups of hormones, what are their differences?

1. amino acid derivatives2. peptide hormones3. lipid derivatives- molecular type, synthesis, size

IFN signaling is down regulated during [...] causing [...]

During chronic stress causing the individual to be more prone to developing illnesses

Nuclear receptors are only available to [...]

Membrane diffusible, lipophilic ligands

What receptor normally sits on DNA, inactivating gene expression?

Thyroid hormone receptors

T3 function

Increases metabolism and basal metabolic rate

What does T3 activate?

Sympathetic nervous system


Results in too much thyroid hormonal stimulation

Graves disease

an autoimmune disorder that is caused by hyperthyroidism and is characterized by goiter, hyper functioning thyroid adenoma