1.1.1 Pre-Midterm Biochem - Hormones & Signal Transduction

Front 1

Describe the different types of cell signalling: endocrine, paracrine, neuronal & contact dependent.

Back 1

•Neurotransmitters released by
neurons at synapses.
•Hormones from endocrine glands.
•Paracrine messengers & autocrine signaling.
•Mechanical stimuli (sound & touch)

Front 2

Describe Endocrine Cell Signalling.

Back 2

Two kinds of Hormones:
Peptides - water soluble, unable to pass membranes, must use receptors - Ephinephrine, Norepinephrine, Thyroxine
Steroid hormones - bind to either cytosolic or nuclear receptors influencing gene transcription - Estrogens, Androgens

Front 3

What decides cell sensitivity?

Back 3

Number of hormone receptors.

Front 4

What are amine hormones?

Back 4

Hormones derived from - Tyrosine: epinephrine and norepinephrine, dopamine Tryptophan: Seratonin

Front 5

Describe Paracrine Cell Signalling

Back 5

Hormones not released into the blood stream but exert their effects locally. Autocrine hormones act on the cell that synthesized them.

Front 6

What is a ligand?

Back 6

Any molecule that binds to a binding site.
Agonists: ligands with a stimulatory effect
Antagonists: ligands with inhibitory effects

Front 7

Define Kd and Fractional Occupancy

Back 7

Kd = [hormone] that causes 50% of receptors to be occupied. Kd = 1/2 Bmax. Analogous to Km.
Fractional Occupancy = [HR] / [Rt] i.e. the fraction of all receptors that are occupied by a hormone or drug.

Front 8

Describe the different cell receptor families

Back 8

Ligand (Ion) Gated Channels
G Protein-Linked Receptors
Enzyme-linked Receptors
Steroid Hormone Receptors

Front 9

Describe Ligand-gated channels

Back 9

On binding a signal molecule, the protein receptor opens, allowing a rapid influx of ions into the cytoplasm through a pore.
Example: Nicotinic cholinergic neuroreceptors - found at neuromuscular junctions and allow the movement of Na+ and K+.

Front 10

Describe G Protein-linked receptors

Back 10

Always have seven transmembrane helices. Hormone binding causes the Gα protein to bind GTP causing a conformational change. GTP displaces GDP and the α subunit dissociates from the Gβγ subunit, producing an intracellular second messenger. After, GTP hydrolyzes back to GDP.
GDP Bound - Inactive
GTP Bound - Active

Front 11

What type of recptor utilizes Adenylyl Cyclase? What are the second messengers?

Back 11

G Protein-linked receptor.
Converts ATP to cAMP

Front 12

What type of receptor utilizes Phospholipase C? What is the name of the receptor and the second messenger?

Back 12

G Protein-linked receptor, specifically phosphatidylinositol phosphate (PIP2) producing 1,4,5 triphosphate (IP3) and diacylglycerol (DAG)

Front 13

What type receptor utilizes Glucagon? How does it work?

Back 13

G Protein-linked receptor. Glucagon is secreted by the pancreas when blood sugars are low. In the liver it activates protein kinaseA (PKA) which in turn stimulates glycogenolysis and inhibits hepatic glycolysis(pyruvatekinase).
Receptor Enzyme: Adenylyl Cyclase
Second Messenger: ATP to cAMP & Pi
Activated Enzyme: Protein Kinase A
Action: Use ATP to phosphorylate and inactivate Pyruvate Kinase.

Front 14

Explain which Adrenoceptors the catecholamines Epinephrine and Norepinephrine each use.

Back 14

Receptor__Agonist___Linked Enzyme___Second messenger
α1_______NE≥Epi___Phospholipase C__↑IP3, DAG & Ca++
α2_______NE≥Epi___Adenylate cyclase_↓cAMP (inhibited)
β1_______Epi=NE___Adenylate cyclase_↑cAMP
β 2______ Epi>NE___Adenylate cyclase_↑cAMP

Front 15

Describe the different types of extracellular signal molecules

Back 15

hormones
growth factors
extra-cellular matrix components
cytokines
chemokines
neurotransmitters
neurotrophins
reactive oxygen species
other electronically-activated compounds

Front 16

Describe how cholera toxin modifies Gs.

Back 16

It consists of 6 subunits.
A is enzymatically active and connected to B in a disulfide bond.
B consists of five protein chains that aid the receptor in binding to ganglioside receptors on host cells.
A detaches and rebosylates the α subunit of the G-Protein (binds ADP-ribose moeity).
This activates adenylyl cyclase.
Intracellular cAMP levels rise, stimulating water and electrolytes to enter the gut lumen.
You die of diarrhoea and dehydration.

Front 17

List 3 receptors using cAMP as second messengers

Back 17

•β-adrenergic receptors are found on sarcolemma.
•Binds epinephrine resulting in activation of adenylate cyclase.
•cAMP is a positive allosteric effector of cAMP dependent protein kinase (protein kinase A).

Front 18

List 3 functions of Alpha Adrenergic receptors

Back 18

Alpha Receptor (lower energy):
Vasoconstriction
Intestinal relaxation
Iris dilation

Front 19

List 5 functions of Beta Adrenergic receptors

Back 19

Beta Receptor (raise energy):
Vasodilation
Cardio Acceleration
Bronchiodilation
Lipolysis
Glycogenolysis (in liver)

Front 20

What type of Adrenergic receptors are in the heart? Name one drug that affects them.

Back 20

There are only Beta receptors in the heart. Beta blockers like Propranolol or Atenolol can be used to regulate cardiac arrhythmias

Front 21

Discuss the role of IP3

Back 21

Inositol trisphosphate, is a secondary messenger molecule. Phospholipase C catalyzes the hydrolysis of PIP2 to IP3and diacylglycerol (DAG).
IP3stimulates the release of Ca2+ from the ER calcium reservoir.
Ca2+forms a complex with calmodulin.
Calcium-calmodulin complex activates a cystolic protein kinase for phosphorylation of a target enzyme.

Front 22

Discuss the role of DAG

Back 22

Diacylglyceride, (DAG) remains bound to the plasma membrane where it activates a membrane-bound protein kinase C (PKC).
PKC is involved in the phosphorylation of a number
of target proteins and may phosphorylate channel proteins that control the flow of Ca2+in and out of the cell

Front 23

Describe Enzyme-linked receptors.

Back 23

•Most consist of a single transmembrane protein.
•The catalytic portion is usually on the intracellular side.
•In almost all cases these phosphorylate intracellular proteins.

Front 24

Describe the Insulin Enzyme-linked receptor.

Back 24

Autophosphorylation: A process that phosphorylates tyrosine residues and insulin receptor substrate [IRS] proteins as well as other insulin receptors inside the cell.
The Insulin Enzyme-linked receptor is a tetrameric protein (two α-& two β-subunits with disulphide bonds) where the β-subunits have tyrosine kinase activity and binding insulin to α-subunits stimulates that same activity. Phosphorylation of insulin receptor substrate (IRS) proteins mediates changes in cellular function.

Front 25

What functions does Insulin upregulate?

Back 25

Glycose Uptake
Glycogen Synthesis
Protein Synthesis
Fat Synthesis

Front 26

What functions does insulin downregulate?

Back 26

Glyconeogenesis
Glycogenolysis
Lipolysis

Front 27

Describe Lipid-soluble hormones

Back 27

Cross plasma membranes and interact with target intracellular cytoplasmic / nuclear receptors.

Transcription factors that bind to regulatory regions of DNA may activate or repress specific genes.
Lipid soluble hormones have a relatively long T1/2 persisting in the blood for hours.

Front 28

Describe the importance of Nitrous Oxide

Back 28

Diffuses across plasma membranes & interacts with a soluble nitric oxide receptor that has guanylatecyclase activity.

Involved in regulating blood flow & blood pressure.

Active ingredient of nitroglycerin, used to treat angina pectoris.

Front 29

What is the immediate cellular response to insulin in adipose and muscle tissue?

Back 29

A rapid increase in glucose transport into the cytoplasm (seconds).