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Cells are the basic structural & functional unit highly structured and contain
membrane bound nucleus and organelles with distinct functions

Cytoskeleton fibers, microtubules and intermediate filaments comprised of actin,

tubulin and keratins help to maintain the organization of the cytoplasm, enable
organelle and vesicle movement within the cytoplasm, help define the shape of cells,
and undergo remodeling during cell movement and replication.

There are three major motor proteins in cells; myosin is associated with the actin
cytoskeleton, and kinesin and dynein are associated with microtubules. Together
these motors and protein filaments/fibers maintain the organization of the
cytoplasm, enable organelle and vesicle movement within the cytoplasm, help define
the shape of cells. There are also involved in cell attachment and cell movement.

Kinesins and cytoplasmic dynein move organelles, vesicles and protein cargos along
microtubules and maintain the intracellular organization of the cytoplasm. Kinesins
typically move cargo from the cell interior towards the periphery of the cells,
anterograde transport. Dynein moves cargo from the cell periphery to towards the
cell interior, retrograde transport.

Cells are open systems that exchange energy and matter with their surroundings.
Extract energy/matter from their environment and metabolize/convert them to waste
products (catabolic) or use the energy to move and perform functions (anabolic) replicate DNA, transcribe mRNA and translate proteins . ATP is the shared chemical
intermediate linking energy-releasing and energy-consuming cellular processes.
NADPH is an electron carrying cofactor that collects electrons from oxidative
reactions and then donates them to reducing reactions during biosynthesis. Present
at low concentrations these cofactors are essential to anabolic reactions and must be
regenerated by catabolic reactions.

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Amino acids, nitrogenous bases, sugars and lipids are the building blocks of
macromolecules, supramolecular structures and cells.

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The organelles and other large structures of the cell are composed of supramolecular
complexes (DNA & proteins/ Lipids & proteins) that are in turn made up of smaller
macromolecules (Proteins, DNA, & lipid bilayers) made from smaller monomers
(amino acids, nucleotide & lipids).

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The complementary anti-parallel strands of DNA follow base pairing rules; the basepaired anti-parallel strands differ in base composition and also differ in in sequence
when each chain is read 5 to 3. The linear sequence of deoxynucleotides arranged in
a precise sequence encodes the genetic information. Two of the polymeric stands
form the DNA double helix in which each deoxynucleotide in one strand pairs
specifically with a complimentary deoxynucleotide in the opposite strand. Before the
cell divides, the two strands separate and each serves as a template for the synthesis
of a new, complementary strand, generating two identical double-helixal molecules,
one for each daughter cell.

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DNA is Transcribed into mRNA and that is Translated into Proteins. DNA stores the
genetic information its sequence of nucleotides from which all other cellular
components are generated.

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Signals from the environment must traverse the plasma membrane and sometimes
additional intracellular membranes such as the nuclear envelope to trigger a
response.

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Phospholipids are composed from a glycerol backbone with two fatty acid side chains
of varying length and degree of saturation at two positions and a polar head group
linked through a phosphate at the third position.

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The polar hydrophilic head group and hydrophobic fatty acid side chains dictate how
phospholipids behave in water. In micelles the hydrophobic fatty acids are
sequestered in the interior of the sphere. In bilayers the polar side chains are at the
surface exposed to the water and the acyl side chains are directed towards each
other. In some cases bilayers fold upon themselves to form a 3-D liposome sphere
with an aqueous cavity in the center.

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Fatty acyl side chains in the interior of the membranes form a fluid hydrophobic
region. Integral membrane proteins are immersed in the lipid held by hydrophobic
interactions with their non-polar amino acids side chains. Both proteins and lipids
are free to move laterally in the plane of the membrane bilayer, but movement from
one leaflet (side) of the bilayer to the other is restricted. Carbohydrate moieties
attached to some proteins are exposed at the external surface of the mebrane.

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found in different compartments based on conditions

Three types of membrane protein integral, peripheral and amphitropic

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Six classes of integral membrane protein classified by the position of the NH- and
COOH-terminus, the number of transmembrane helicies, the number of polypeptides
involved, and the surface that the lipid anchor is attached to. Palmitoylation,
farnesylation and myristoylation are post translational modifications that can direct
proteins to the inner surface of the plasma membrane. Glycosyl
phosphatididylinositol anchored proteins are always on the external surface.

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Single polypeptide chain folds into seven hydrophobic alpha-helices that traverse the
membrane roughly perpendicular to the plane of membrane. The 7TM helices cluster
together surrounded by the acyl side chains of the lipids. The corresponding
hydropathy plot color coded by the 7TM helices shows the hydropathy index a
measure of the free energy change accompanying the movement of an amino acid
from a hydrophobic solvent into water.

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Stable association of sphingolipids and cholesterol in the outer leaflet produce a

microdomain that is slightly thicker and enriched for membrane proteins GPI
anchored proteins on the outside and fatty acyl-linked proteins on the inside.
Inwardly curved rafts called caveolae are enriched for caveolin and prenylated
proteins such as Ras.

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GPCRs 3 common features 7TM domains, an associated GTP-binding protein that

activates an enzyme/ion channel to generate second messengers

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Affinity increases as kd
decreases

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cAMP-dependent activation of PKA leads to the subsequent phosphorylation and

activation of enzymes including other kinases signaling cascade

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1. Epinephrine activation of the GPCR expressed in liver cells initiates a cascade of

signaling events involving activation of adenylyl cyclase, increased cAMP levels,
activation of PKA and downstream kinases that elevates the production of glucose
from glycogen. 2. Epinephrine activation of the GPCR expressed cells initiates a
cascade of signaling events involving activation of adenylyl cyclase, increased cAMP
levels, activation of PKA and downstream kinases that mediate a number of
functional responses.

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Ca2+ transients measured by the Ca2+ sensitive dye Fura-2. Ca2+ mobilization regulates
numerous downstream signaling pathways through the regulation of Ca2+ dependent
enzymes, kinases, and ion channels.

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GPCR transduce a large number of signals.

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Almost 800 GPCR genes; Class A/Family1 Rhodopsin-like GPCR largest family, class
B/Family 2 secretin-like, and class C/Family 3 metabatropic glutamate (mGluR) family.
271 Orphan GPCRs endogenous ligand as yet not identified

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There may be multiple GPCR sub-types that respond to identical ligands

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GPCR specificity maintained by differential expression and distribution within tissues

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