Biol 2424 Human Phys
1
What are the 3 major processes that use energy?
PLASMALEMMA TRANSPORT Ch 5
Cells need both inorganic (oxygen, cofactors, etc.) & organic substances (CLiP oNs) to survive.
- Transport of substances is necessary to maintain a relatively constant internal environment—homeostasis
- Cells have membranes (or plasmalemma) that serve as barriers between the ECF & ICF
What are the 3 parts of the ECF?
Plasmalemma Fxs
1. Physical isolation & containment
2. Regulation of exchange with environment
3. Communication between the cell & its environment
4. Structural support
STRUCTURE OF THE PLASMALEMMA: THE PHOSPHOLIPID BILAYER
- membranes are mostly lipids & proteins
- Fluid Mosaic Model: membrane not a rigid structure—like liquid cooking oil; allows shape change; transport
processes dependent on its fluidity
- membrane lipids form a physical & chemical barrier between the cytoplasm & ECF
- membrane proteins may be tightly or loosely bound to the membrane
membrane-spanning = integral; associated = extrinsic/peripheral
- membrane not held by chemical bonds, each phospholipid molecule is able to twirl around rapidly, as well as
move about within their own half of the layer, much like skaters on a crowded rink
- hydrophilic heads, hydrophobic tails serve as a barrier to passage of water-soluble substances between the ICF
& ECF. Water soluble substances cannot dissolve in and pass through the lipid bilayer, but water molecules
themselves are small enough to pass between the phospholipids
1. Cholesterol is nonpolar so it’s tucked in between the fatty acid tails of the phospholipid molecules. Cholesterol
prevents the fatty acid chains from packing together & crystallizing, a process that would drastically reduce membrane
fluidity; makes the plasmalemma impermeable to some small water soluble (polar) molecules; and keeps the
membrane flexible over a wide range of temperatures.
2. Carbohydrates: aid in cell recognition & communication, as well as structural integrity; the “sugar coating” of
communication
3. Proteins: variety of types & fxs; proteins are the most diverse biomolecule
- protein channels span membrane to allow passage of water soluble substances that are small enough to enter a
channel, such as ions, to pass through the membrane without coming into direct contact with the hydrophobic lipid
interior. May move tens of millions of atoms/molecules per second. Protein carriers may move 1,000 to a million
atoms/molecules per second.
- protein carriers transfer specific substances unable to cross the membrane on their own. Each carrier can only
transport a particular molecule or closely related molecules. Variation in the kinds of carriers different cells possess
permits them to selectively transport substances across their membranes; carriers are particularly important if the
molecule is big (i.e., can’t diffuse through) HIGHLY SELECTIVE!
e.g.: The thyroid gland requires iodine for the synthesis of thyroxine. Accordingly, the cell membranes of thyroid
gland cells uniquely possess carriers for iodine transport, enabling the essential element to be transported from the
blood into thyroid gland cells. Not all cells have this capability because they have different carrier proteins.
- receptor sites/membrane receptors: recognize & bind with specific molecules in the environment of the cell, which
causes changes in the activity of the cell. In this way, chemical messengers in the blood, such as hormones, are
able to influence only the specific cells that possess receptors for the messenger while having no effect on other
cells, even though every cell is exposed to the messenger.
e.g.: The anterior pituitary gland secretes TSH (thyroid stimulating hormone), which only can attach to the surface
of thyroid gland cells to stimulate secretion of thyroid hormone. No other cells have receptor sites for TSH, so only
thyroid cells are influenced by TSH despite its wide-spread distribution.
- membrane bound enzymes control chemical reactions on the inner and outer surface of the membrane.
- filamentous network is formed by proteins on inner surface of membrane; they are secured to certain internal
proteins of the cytoskeleton = stabilize cell, maintain its shape
Biol 2424 Human Phys
2
- Cell Adhesion Molecules or CAMs protrude from the membrane surface and form loops or other appendages that
the cells use to grip a hold of each other and to connective tissue fibers that interlace between cells. Provide
structural integrity: help hold tissues & organs together.
- some proteins join with carbohydrates, and these glycoproteins are important in the cells ability to recognize "self"
(cells of the same type) and in cell-to-cell interactions.
Membrane Proteins Fxs
1. structural proteins: link membrane to the cytoplasm (maintain shape) & form cell to cell connections that hold cells
together (desmosomes, tight junctions, etc...)
2. enzymes catalyze chemical rxs
3. receptors: part of the body's chemical communication system; some are specific. The molecule that binds to a
receptor is called a ligand (ligament = binder). The binding of a receptor & ligand usually triggers another event at
the membrane, such as activation of a membrane enzyme (e.g., GLUCOSE TRANSPORT). Other receptor types
include ones for cell-to-cell recognition.
4. transporters: move substances across the membrane that cannot directly dissolve through the membrane (channel
proteins & carrier proteins)
Channel proteins have water filled passageways that link the ICF & ECF.
- Only large enough for water, ions, & small molecules, such as urea to pass; specific & selective based mainly
on charge & size
- open channels spend most of their time open
- gated channels spend most of their time closed & are opened by messenger molecules, ligands (chemically
gated), electrical state of the cell (voltage regulated), or by a physical change, such as increased T or a blow
that stretches the membrane & pops the channel open (mechanically gated)
Carrier proteins shuttle substances across, but never form a direct connection between the ICF & ECF
(analogous to a series of locks, as in the Panama Canal). Carrier proteins bind with specific molecules
(substrates) & carry them across the membrane by changing conformation or shape.
- glucose, amino acids, nucleic acids, Na+, K+, Ca+2 may be moved by carriers, as well as channels
5. glycocalyces (composed of glycoproteins & glycolipids) serve to identify the cell as belonging to the organisms & what
specific type of cell it is; important in immune system fx. “Sugar coating of arms” identifies the cell as the body’s own.
Body Fluid Compartments: cell membranes divide the body into different compartments: ICF/interstitial
fluid/plasma/lymph
MOVEMENT ACROSS MEMBRANES:
Membranes are selective about what they let enter & leave the cell based on two mechanisms:
active & passive transport
PASSIVE TRANSPORT requires NO energy use from the cell. No ATP is used:
- types:
diffusion, osmosis, facilitated transport, & carrier mediated transport through channels by carriers or
simply by dissolving/passing through the phospholipid bilayer
- movement of substances relies on kinetic energy
- molecules are always constantly moving (Brownian movement)
- On average, kinetic movement evenly or randomly distributes substances, so it always has a net movement from
area of high concentration to area of lower concentration until equilibrium is reached
- the difference between the [high] & [low] is called a concentration gradient. The math symbol  = gradient. When
molecules move from areas of [high] to [lower], they are said to move down a [ ] .
- passive process with net movement until the concentration is equal everywhere.
CELLULAR DIFFUSION is the process by which some molecules can pass through the membrane via the membrane
itself, thru channels, or carrier proteins.
See Table 5-2 in Silverthorn text for a great review.
Biol 2424 Human Phys
3
Molecular motion is affected by several factors:
1. Higher [  ] leads to more rapid diffusion.
2. Distance, area, & cell volume (can alter shape, invaginate, circulatory system)
3. Heat content (which is measured by T)
4. Pressures exerted by gravity or other natural forces
5. Nature of the medium (highly viscous, high polarity, etc.)
6. Molecular size
At a given heat content, which molecule travels faster: the smaller or larger?
Diffusion occurs when there’s no barrier and may occur when there is a barrier (a membrane).
Cellular diffusion also depends on
1. its ability to dissolve in the lipid bilayer
- uncharged molecules/nonpolar molecules dissolve in the lipid bilayer & can move thru the membrane = O 2, CO2,
fatty acids, alcohols
- charged molecules like Na+ & K+ & polar molecules, such as glucose & urea, have low lipid solubility: lipid bilayer
greatly deters diffusion
- particles that aren’t lipid soluble are too large (generally over 180MW) can’t move through the membrane by
simple diffusion
2. the amount of surface area of the membrane: the larger the surface area, the more molecules can diffuse across per
unit time (e.g., compare intestinal villi to cheek cells; also emphysema).
3. the thickness of the membrane: thinner membrane results in faster diffusion rate
OSMOSIS is also a passive means of transport by which water moves between fluid compartments. Remember it is a
good solvent for all living matter & moves freely between the cells & the ECF. The amount of water in any individual
varies but the "standard" 21 yr old male at 70kg is 60% of body weight (92.4lbs). You must have water and a membrane
to do osmosis!
1. The movement of water molecules through a selectively permeable membrane from areas of higher [water] to areas
to lower [water]. H2O molecules pass thru pores of integral proteins.
2. The movement of water thru a membrane produces a pressure called osmotic pressure, which is an important force
in the movement of water within the body.
3. e.g., for erythrocytes to maintain their shape, the cell must be in an isotonic solution = [ ] of water & solute the
same on both sides of the membrane; 0.9% NaCl is isotonic to body cells.
What osmolarity is 0.9% NaCl equal to?
- a cell bathed in a hypotonic solution will rupture: osmotic pressure outside cell is greater, so water flows into the cell
(cell goes boom boom): lysis is the breaking of the cell membrane mechanically or chemically
- a cell bathed in a hypertonic solution will crenate: water moves out of the cell; the osmotic pressure is greater in
the cell, so water flows out to the lower pressure of the ECF
“Cells in hypertone crenate to a crinkly state.”
Remember 3 Rules for Osmosis:
Water moves from:
1. High [H2O] to low [H2O]
2. Low [solute] to high [solute]  this can be either percent [ ] or molar [ ]
3. Low omolarity to high osmolarity
FILTRATION: movement of solvents across a selectively permeable membrane by mechanical pressure (i.e., gravity or
pumping action)
- movement from high pressure to low pressure is a passive process, but an active process is usually used to setup
up a gradient.
- filtration is used to move substances from capillaries to the interstitial fluid environment.
- Also used in kidneys to push waste products from blood into the nephron to form urine
Remember the glomerulus in Bowman’s capsule?
Biol 2424 Human Phys
4
FACILITATED DIFFUSION
- large lipid insoluble molecules move across the plasmalemma with the assistance of integral proteins (imbedded in the
plasmalemma)
e.g., glucose attaches to a channel protein, which changes the channel’s shape, and glucose can now pass through at
no ATP cost—it’s a passive process!!! Nucleic acid is another molecule that is transported via facilitated diffusion.
Your blood glucose levels are low. What organ first resupplies glucose to the blood? What does it do to get glucose?
How is the glucose transported out of its cells?
Carrier Mediated Transport can be active or passive: active requires energy, whereas passive is done for free via [ ]
gradients (i.e. No NRG). Both regulate what goes in & out of cells.
1. Specificity refers to the ability of a carrier to move only one molecule or a group of closely related molecules e.g.,
glucose, aa's, nucleic acids.
2. Competition competes &/or blocks; e.g., poisons/medicines, beta blockers for BP
3. Saturation occurs when a group of membrane carrier proteins are transporting substrates at their maximum rate;
e.g., a crowd loading at a bus stop
In passive carrier mediated transport, diffusion stops when the system reaches equilibrium (the [ ] inside the cell equals
the [ ] outside the cell): large & lipid insoluble particles move across the membrane with the assistance of integral
proteins that are embedded in the membrane.
A uniport is a protein transporter that carries only one substrate, and a cotransport protein is one that moves 2 (or 3)
different molecules at the same time; symport is when the molecules are transported in the same direction; antiport is
when the molecules are transported in the opposite directions.
ACTIVE TRANSPORT requires energy expenditure from the cell (ATP); moves substances against their [ ] across the
plasmalemma; like pushing a ball up a hill; 40% of all ATP is used for active transport. ATPases (ATP enzymes)
hydrolyze ATP into ADP & inorganic phosphate, releasing energy to change the conformation of the protein gate; e.g.,
Na-K-ATPase; aka Na/K pump. The Na/K pump trades 3 Na for 2 K to maintain a low [ Na ] in the ICF.
- transport mechanism moves substances from an area of [ low ] to an area of [ high ]
- movement is against the [ ] 
- e.g., the epithelial lining of the small intestine & kidney tubules moves glucose from the side of lower to the side of
higher concentration (nephron lumen to peritubular capillary bed).
- all cells extrude Ca+2 into the ECF to maintain an ICF [Ca+2] that is 1,000 to 10,000 times lower than the ECF; aids in
cytoskeletal, cilia, & flagella movement & muscular contraction; Ca+2 is impermeable to the cell membrane, so the
cell has to spend energy to extrude it to prevent a harmful build up
For a substance to be actively transported into/out of the cell, it (or a messenger) binds to an active site on a membrane
protein & starts the pump; an active site is a region of the protein that binds to a particular molecule (specificity) &
triggers a chemical rx that changes the conformation/shape of the protein.
Fxs of Active transport
- creates a state of disequilibrium by making concentration differences across the plasmalemma more pronounced.
- vital to maintaining some ions at particular concentrations in the cells, & is especially important for skeletal, smooth, &
cardiac muscles, & nerve tissue.
Primary (direct) Active Transport: Sodium/Potassium Exchange "Pump" maintains [ ] differences
- Na is concentrated in ECF, pumped there from ICF
- K is concentrated in ICF, pumped there from ECF
e.g., chemical messenger binds to protein receptor, causing changes in cell & a release of ATP, which in turn
causes a change in the protein carrier, & the molecule is released on other side of membrane.
- aids in transport of other molecules
- can be adjusted to regulate the energy expenditure & BMR of the body
- the Na & K gradients across the cell membranes of nerve & muscle cells are used to produce electrical impulses =
action potentials: important for responses.
Biol 2424 Human Phys
5
- osmotic reasons: if the pumps stopped fx, the increased Na within the cells would draw increased water, damaging
the cells.
Secondary (Indirect) Active Transport
In secondary active transport, the energy to “push” molecules against their [ ]  comes from potential energy stored in a
[ ] . The energy needed for the "uphill” movement of a molecule or ion is obtained from the "downhill" transport of Na +
into the cell. ATP is directly needed to keep Na+ low in the ICF & high in the ECF (Na/K pump), so indirectly the Na+
gradient that secondary active transport runs on has a cost.
ROLLER COASTER - ELEVATOR ANALOGY
RECYCLING WATER THROUGH A SLOUGH TO GET THE GOLD$$$$
- The diffusion of Na into the cell (from ECF where its concentration is high to the ICF where its concentration is low)
may power the uphill movement of a different ion or molecule into the cell, or it may power the movement of an ion or
molecule out of the cell.
- In epithelial cells of the small intestine & kidney tubules, glucose is transported against its concentration gradient by a
carrier that requires the simultaneous bonding of Na. Glucose & Na move in the same direction (into the cell) as a
result of the Na gradient created by the Na/K pumps.
Phagocytosis: ingestion of particulate matter by fusing the plasmalemma to it, surrounding it with the plasmalemma, &
enclosing it into a vesicle that is brought into the cytoplasm. In humans, only phagocytic leukocytes “eat” (bacteria) this
way. Plasmalemma & cytoplasm extrude to engulf a particular particle. Lots of ATP needed to move the
cytoskeleton & transport the vesicles. Phagocytosis must be induced by “bumping” into a bacterium. Endocytosis is
always going on.
Endocytosis: the cell membrane indents & surrounds the substance (invagination), which is then brought into the cell;
assisted by cytoskeletal attachments. Costs ATP. Plasmalemma & cytoplasm invaginate.
- can be unselective: pinocytosis (pino = drink) is a random sampling of ECF. A “grab bag meal,” or luck of the draw.
- can be receptor-mediated = very specific. Receptor mediated endocytosis transports such substances as protein
hormones, growth factors, antibodies, and carrier proteins for iron & cholesterol.
Exocytosis: vesicles fuse to plasmalemma to secrete large, lipophobic molecules (proteins) and to excrete lysosome
wastes. Costs ATP. Goblet cells continually release mucus in the stomach & intestine through exocytosis.
- intracellular vesicles move to the cell membrane, fuse with it, & the open to expose their content to the ECF (barf it up)
- cells secrete their product which is used in other parts of the body: mucus, HCl, enzymes, hormones, excrete wastes
Remember to get to the ECF from outside the body, substances have to cross two membrane layers: the apical & basal
part of the epithelial cell. Transporting epithelial cells, such as those of the kidney & intestine, are said to be polarized
because they have different membrane proteins on their apical & basal surfaces. This polarization allows one-way
movement of molecules across the epithelium. See p146 Fig. 5-28. Larger molecules cross by transcytosis, which is a
combination of endocytosis, vesicular transport, & exocytosis. Transcytosis is an active & passive process. Infants
absorb maternal antibodies from her milk through transcytosis—no damage is done to the protein to move it.
Diagram Negative Feedback Loops for Blood GLU Levels
Biol 2424 Human Phys
6
A special example: Metabolic Effects of Insulin
Glucose: Receptor Mediated Facilitated Transport
1. Glucose is needed by many of the body’s cells to produce ATP for energy storage. The problem though is that GLU
is a big molecule & has a sophisticated mechanism to get into cells using insulin.
Where exactly is insulin produced?
2. Insulin is a hormone secreted by the pancreas which has many effects on the body. The primary targets for insulin
are the liver, adipose tissue, & skeletal Mm. Some tissues, including the brain (special protein carriers) &
transporting epithelia, do not respond to insulin & have other means of transporting GLU (transcytosis & vesicular
transport).
3. In the target tissues of insulin, the cellular response generally takes 1 of 2 forms:
- increased uptake of glucose from the blood into the cell
- increased use of glucose for energy & synthesis.
- promotes glycogen, protein, & fat synthesis
4. Mechanism
- when insulin combines with its receptors on adipose & muscle tissue, GLUT-4 transporters stored in the cytoplasm
in vesicles are translocated to the cell membrane & inserted by exocytosis.
- the cells can then take up glucose from the interstitial fluid by facilitated diffusion.
- When the insulin-receptor complex is inactivated, the GLUT-4 transporters are withdrawn from the membrane, &
glucose entry into the cell declines.
- Cells maintain [ low ] of GLU on the inside by converting it to glucose-6-phosphate to facilitate further transporting
Diagram Insulin & Facilitated Diffusion of GLU