WKI Sales Training Feb 2014 - page 90

Chapter Summary
15
• All cells erect a lipid barrier (the
plasma membrane
) to separate the inside of the cell from the outside, and then selec-
tively modify the ionic composition in the intracellular environment to facilitate the biochemical reactions that sustain life.
Intracellular fluid
contains very low concentrations of Ca
2
compared with
extracellular fluid
. Na concentrations are
also lower inside, but K levels are higher.
• The plasma membrane contains three principal lipid types:
phospholipids
,
cholesterol
, and
glycolipids
. Phospholipids
dominate the structure, cholesterol adds strength, and glycolipids mediate interactions with other cells.
• Movement across membranes occurs primarily by
diffusion
. Diffusion rate is dependent on the transmembrane
concen-
tration difference
, molecular size, membrane thickness and surface area, temperature, viscosity of the solution through
which the molecule must diffuse, and the molecule’s solubility in lipid (
partition coefficient
).
• Integral membrane proteins such as
pores
,
channels
, and
carriers
provide pathways by which hydrophilic molecules
may cross the lipid barrier.
• Pores are always open and are rare, the principal example being
aquaporin
, a ubiquitous water channel. Channels are
regulated pores that open transiently to allow passage of small ions, such as Na , Ca
2
, K , and Cl . Movement through
pores and channels occurs by simple diffusion down electrical and chemical concentration gradients (
electrochemical
gradient
).
• Carriers selectively bind ions and small organic solutes, carry them across the membrane, and then release them on
the opposite side. Carriers operate by two modes of transport:
facilitated diffusion
and
active transport
. Facilitated
diffusion moves solutes “downhill” in the direction of the electrochemical gradients (e.g., glucose transport by the GLUT
transporter family). Active transport uses energy to move solutes “uphill” from an area containing low solute concentra-
tion to an area of higher concentration.
Primary active transporters
, or
pumps
, use adenosine triphosphate to drive solutes uphill against their electrochemi-
cal gradient. Pumps include the Na -K ATPase that is present in all cells, Ca
2
ATPases, and the H -K ATPase.
Secondary active transporters
move solutes uphill by harnessing the energy inherent in electrochemical gradients for
other ions.
Exchangers
move two solutes across the membrane in opposite directions (e.g., the Na -Ca
2
exchanger).
Cotransporters
(e.g., Na -K -2Cl cotransporter and the Na -glucose cotransporter) move two or more solutes in the
same direction.
• The plasma membrane also contains receptor proteins that allow cells to communicate with each other using chemical
messages. Signaling can occur over long distances via the release of
hormones
(e.g., insulin) into the bloodstream.
Cells that are in close proximity to each other communicate using
paracrines
(e.g., nitric oxide).
Autocrines
are chemi-
cal signals that target the same cell that released them.
Receptor binding
is transduced in a variety of ways.
Ligand-gated ion channels
transduce binding using changes
in membrane potential. Other receptor classes release
G proteins
to activate or inhibit
second messenger
pathways.
Many receptors possess intrinsic kinase activity and signal occupancy through protein phosphorylation. A fourth class of
receptor is located inside the cell. Intracellular receptors affect levels of gene expression when a message binds.
• G proteins modulate two major second-messenger cascades. The first involves
cyclic adenosine monophosphate
(
cAMP
) formation by
adenylyl cyclase
. cAMP acts primarily through regulation of
protein kinase A
and protein phos-
phorylation.
• Other G proteins activate
phospholipase C
and cause the release of
inositol trisphosphate
(
IP
3
) and
diacylglycerol
(
DAG
). IP
3
, in turn, initiates Ca
2
release from intracellular stores. Ca
2
then binds to calmodulin and activates Ca
2
-
dependent transduction pathways. Ca
2
and DAG together activate protein kinase C and cause phosphorylation of target
proteins.
• Receptors with intrinsic
tyrosine kinase
activity autophosphorylate when the message binds. This allows them to com-
plex with adapter proteins that initiate signal cascades affecting cell growth and differentiation.
Intracellular receptors
translocate to the nucleus and bind to
hormone response elements
within the promoter region
of target genes. Cell function is altered through increased levels of target gene expression.
Chapter Summary
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