BSC-2010 Lecture Notes - Lecture 16: Blood Sugar, Protein Kinase A, Duodenum

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2 Dec 2016

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Chemical Signals
Chemical Signals
Within cells
2nd messengers and related molecular pathways
Between cells
In an organism
Some 2nd messengers
Between organisms
Communication been cells in direct contact — review
Cell junctions
Gap junctions between adjacent cells that let chemical and electrical signals
pass between cells
The electrical signals are ion currents, involve ions
Cell-cell recognition
Mechanical chemical signals that are very specific
Involves the binding of one surface molecule on one cell into another surface
molecule on another cell
Typically proteins and glycoproteins, can involve lipids as well
Crucial for the development of the nervous system
Local and long-distance cell communication by chemical signaling in animals
Paracrine Signaling
One cell releases a chemical and this chemical signal reacts on adjacent
cells that are capable of responding to it
Synaptic Signaling
The chemicals that are released are only release at the synapse; they only
influence the adjacent target cell
Endocrine (hormonal) signaling
Exocytosis, neurotransmission
The hormone chemicals enter the blood and causes a response in any cell
that is capable of responding to it
Examples: histamine, neurotransmitters ACh, GABA
Electrical signaling, too! (synaptic signaling)
Neurons, nervous system, and muscle
One example of chemical communication between individuals — Dictyostelium
To form fruiting bodies in response to a concentration gradient of a chemical
signal released by other Dicty
Receptor location varies with hormone type: water soluble vs. lipid soluble hormones
Steroid hormones: Lipophilic
Can diuse across membranes without a transporter, but bind to proteins for
transport in blood, cytoplasm
Major endocrine glands in humans: Hormonal signaling
Pineal gland
Pituitary gland
Thyroid gland
Parathyroid glands
Adrenal glands
Dierence in hormone solubility and structure
Water-soluble: hydrophilic
Lipid-soluble: hydrophobic
A simple endocrine pathway
Stimulus excites endocrine cell
Hormones released
Reach target cells
Target cells issue a response
Results in a negative feedback loop
Example: secretin signaling
Low pH in duodenum (stimulus)
S cells of duodenum (endocrine cells)
Secretin (hormone)
Pancreatic cells (target cells)
Bicarbonate release (response)
Homeostatic (negative feedback) regulation of blood glucose (cellular fuel)
Hyperglycemia - an increase of blood glucose concentration
Lets to beta cells in the pancreas, results in insulin being released
Hypoglycemia - a decrease of blood glucose concentration
Increase glycogen breakdown and releases of glucose into blood (increases
blood glucose)
Roles of Parathyroid Hormone (PTH) in calcium home states in mammals
Normal blood Ca2 level
Blood Ca2 level falls
Parathyroid glands release PTH
PTH stimulates the releases of Ca2 from the bones
PTH stimulates Ca2 uptake and promotes activation of vitamin D
Active vitamin D increases Ca2
Blood Ca2 level rises
A chemical signal can cause dierent responses in dierent cell types
Dierent responses are due to:
Dierent eector (response) machinery
Dierent intracellular signal transduction pathways
Dierent receptors in plasma membrane
What Happens after a cell receives a chemical signal?
Overview of Cell Signaling —> Signal Transduction
(1) Reception
Receptor and signaling molecule
(2) Transduction
Relay molecules
(3) Response
Activation of cellular response
In the cytoplasm
Phosphorylation Cascade — an amplifying transduction pathway
A signaling molecule bonds to a receptor
The receptor activates relay molecule
Active protein kinases transfer a phosphate from ATP and covalently bond to some
particularly protein
Makes inactive protein, an active protein
What is the purpose of this cascade? There is an amplification that goes on
G-Protein-Coupled Receptor (GCPR) function
G-protein-coupled receptors are integral membrane proteins:
7 transmembrane alpha-helices
Receptor Tyrosine Kinases - receptor and kinase are parts of same TM protein
A signaling molecule (ligand) binds to the ligand-binding site on receptor tyrosine
kinase proteins (inactive monomers)
The separate receptor tyrosine kinase proteins join together to form a dimer
Activated tyrosine kinase regions (unphosphorylated dimer)
ATP becomes ADP to form a…
Fully activated receptor tyrosine kinase (phosphorylated dimer?
Inactive relay proteins bind to the phosphorylated dimer creating cellular responses
Cyclic AMP (cAMP) is an important second messenger
Adenylyl cyclase — enzyme for synthesizing cAMP (from ATP)
An example of an enzyme activate by G-proteins
Phosphodiesterase — enzyme for degrading cAMP to (AMPT)
cAMP binds to and allosterically activates cAMP-dependent protein kinase A (PKA)
Maintenance of calcium ion (Ca2+) concentrations in an animal cell
Calcium ion (Ca2+) is another important second messenger
Note storage of Ca2+ in some organelles
Also note LARGE electrochemical gradient for Ca2+
Ligand-Gated Ion Channel
(1) Signaling molecule, a ligand, bonds to the active site on a ligand-gated ion channel
(2) The gate is now opened, ions can flow from the external environment into the cell
(3) The ligand detached from the channel and the gates is closed
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