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Chapter 5

PSL201Y1 Chapter Notes - Chapter 5: Signal Transduction, Lipid Bilayer, Paracrine Signalling


Department
Physiology
Course Code
PSL201Y1
Professor
Michelle French
Chapter
5

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Almost all body functions require communication
between cells. In a few instances, cells are
physically linked by gap junctions, the majority
of cells however communicate via chemical
messengers.
Direct communication through gap Junctions
Gap junctions link adjacent cells and are
formed by connexons. They form channels and
allow ions to pass through from one cell to
another.
Indirect communication through chemical
messengers
More commonly, cells communicate
chemically in the form of ligands; molecules that
bind to proteins reversibly. A cell secretes a
chemical into the interstitial fluid. The target cell
responds to the chemical messenger because
of its receptor proteins. This leads to signal
transduction; the response of the target cell to
the chemicals from the first cell.
The strength of the signal transduction increases
as the number of bound receptors increase.
Chemical messengers can be classified
according to their functions or chemical
structure.
Functional classification of chemical
messengers.
They are three categories based on their
functions:
Paracrines
Neurotransmitters
Hormones (Endocrines)
Paracrines
These are chemicals that communicate with
neighboring cells.The target cell must be very
close, such that when the paracrine is secreted,
it reaches the target cell by simple diusion.
Paracrines include, growth factors, clotting
factors and cytokines.
Growth factors are proteins that stimulate
proliferation and dierentiation of cells. This is
the multiplication and segregation of dierent
cells.
Clotting factors are proteins that stimulate
formation of a blood clot.
Cytokines are peptides released from immune
cells. The coordinate the body’s defense
against infections. They are some paracrine
however, that function like hormones, traveling
far distances to their target cells. Autocrines are
a sub class of paracrines. They act on the same
cell that secreted them. That is, the secretory
cell is also the target cell.
Neurotransmitters
These are chemicals released into interstitial
fluid by neurons. They are released from the
axon terminal on the neuron cell. This is often
also referred to as synaptic signaling. This is
because the space between the axon and the
target cell is called the synapse.
The cell that releases the neuron is referred to as
the presynaptic neuron while the target
cell/neuron/gland, is called the postsynaptic
cell.
Hormones
These are chemicals released from
Endocrine glands. They travel by diusion also.
They communicate with target cells which are at
a far distance from the endocrine gland. The
hormone travels through the blood stream but
only cell with specific receptors for said hormone
are able to respond and act as target cells.
Chemical Classification of Messengers
The chemical structure of the messenger
determines its mechanisms of synthesis, release,
transport and signal transduction. The most
important chemical characteristic is it’s polarity.
This is because of the lipid bilayer, which is non
polar.
Lipophilic molecules are lipid soluble and readily
cross the plasma membrane but they do not
dissolve in plasma (due to water content).
Lipophobic molecules are water soluble and
dissolve in plasma but they do not cross the
plasma membrane.
They are 5 main distributions according to
chemical structure:
Amino acids
Amines
Peptides/Proteins
Steroids
Eicosanoids
Amino Acids
The amino acids Glutamate, Aspartate,
Glycine and Gamma aminobutyric acid (GABA)
are classified as chemical messengers because
they function as neurotransmitters in the brain
and spinal cord. All the amino acids listed above
belong to the 20 amino acids found in the body
apart from GABA which belongs to a a class of
amino acids called gamma amino acids. They
are lipophobic.
Amine Messengers
Amines are derived from amino acids and are
so named because they contain the amide group
in the chemistry (-NH2). They include a group of
compounds called catecholamines (six carbon
ring), which contain a catechol group. They are
derived from the amino acids tyrosine. These
include dopamine, serotonin and norepinephrine
as neurotransmitters and epinephrine as a
hormone. All the amines are hydrophilic apart
from the thyroid hormones.
Peptide/Protein Messengers
Most chemical messengers are polypeptides.
They are either proteins or peptides based on
their size. A peptide is made up of 50 or less
amino acids, whereas a protein is anything
above 50 amino acids in length. They are
hydrophilic.
Steroid Messengers
Steroids are a class of compounds derived
from cholesterol. All of the steroid messengers
in the body functions as hormones. Cholesterol
is a lipid with a distinctive four ring structure.
This makes it hydrophobic or lipophilic.
Eicosanoid Messengers
They include a variety of paracrines that are
produced by almost every cell in the body. They
are derivatives of arachidonic acid, a 20 carbon
fatty acid that is found in various plasma
membranes. They are therefore hydrophobic.
They consists of prostglandins, leukotrienes and
thromboxanes.
Synthesis and Release of Chemical
Messengers
The synthesis and release for chemical
messengers are quite similar within a chemical
class.
Amino Acids.
The 4 amino acids that function as
neurotransmitters must be synthesized within
the neuron that secretes them. Glutamate and
Aspartate are synthesized in the process of
glycolysis, pyruvate oxidation and the krebs
cycle. They are made in the intermediary steps
of the krebs cycle. Glycine is synthesized from a
glycolytic intermediate, 3-phosphoglycerate, in
a series of 4 reactions. GABA is synthesized
from a single reaction.
Following synthesis, they are transported into
vesicles, where they are stored until they are
released by exocytosis.
Amines
All amines are derived from amino acids
except the thyroid hormones. This is done in the
secretory cell by a series of enzyme catalyses
reactions.
Peptides and Proteins
Peptides and proteins are synthesized the
same way as other proteins destined for
secretion. mRNA serves as the template that
codes for the amino acid sequence in the
peptide or protein, Translation of the mRNA
begins on the ribosomes that are found in a free
state in the cytosol.
Steroids
Steroid messengers are synthesized from
cholesterol in a series of reactions catalyzed by
enzymes located in the smooth endoplasmic
reticulum or mitochondria. during this, the
cholesterol is modified but it retains it’s four ring
structure and it’s hydrophobic character.
Transport of Messengers
After release, messenger must reach, then
bind to receptors on the target cell for
signal transfer.
Hormones can be transported in the blood
either in dissolved form or bound to
carrier proteins. Messenger must be
hydrophilic to be transported in dissolved
form. Peptides and amines are transferred
in this manner. Steroids and the thyroid
hormones need a carrier protein for
transfer as they are hydrophobic
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