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Cells: The Living Units: Part B
3 Cells: The Living Units: Part B
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Membrane Transport: Active Processes
Two types of active processes: Active transport Vesicular transport Both use ATP to move solutes across a living plasma membrane
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Requires carrier proteins (solute pumps)
Active Transport Requires carrier proteins (solute pumps) Moves solutes against a concentration gradient Types of active transport: Primary active transport Secondary active transport
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Primary Active Transport
Energy from hydrolysis of ATP causes shape change in transport protein so that bound solutes (ions) are “pumped” across the membrane
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Primary Active Transport
Sodium-potassium pump (Na+-K+ ATPase) Located in all plasma membranes Involved in primary and secondary active transport of nutrients and ions Maintains electrochemical gradients essential for functions of muscle and nerve tissues
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Figure 3.10 Extracellular fluid Na+ Na+-K+ pump ATP-binding site K+
Na+ bound Cytoplasm 1 Cytoplasmic Na+ binds to pump protein. P ATP K+ released ADP 6 K+ is released from the pump protein and Na+ sites are ready to bind Na+ again. The cycle repeats. 2 Binding of Na+ promotes phosphorylation of the protein by ATP. Na+ released K+ bound P Pi K+ 5 K+ binding triggers release of the phosphate. Pump protein returns to its original conformation. 3 Phosphorylation causes the protein to change shape, expelling Na+ to the outside. P 4 Extracellular K+ binds to pump protein. Figure 3.10
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1 Extracellular fluid Na+ Na+-K+ pump K+ ATP-binding site Cytoplasm
Cytoplasmic Na+ binds to pump protein. Figure 3.10 step 1
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Na+ bound P ATP ADP 2 Binding of Na+ promotes phosphorylation of the protein by ATP. Figure 3.10 step 2
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Na+ released P Phosphorylation causes the protein to change shape, expelling Na+ to the outside. 3 Figure 3.10 step 3
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K+ P 4 Extracellular K+ binds to pump protein. Figure 3.10 step 4
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K+ bound Pi K+ binding triggers release of the phosphate. Pump protein returns to its original conformation. 5 Figure 3.10 step 5
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K+ released 6 K+ is released from the pump protein and Na+ sites are ready to bind Na+ again. The cycle repeats. Figure 3.10 step 6
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Figure 3.10 Extracellular fluid Na+ Na+-K+ pump ATP-binding site K+
Na+ bound Cytoplasm 1 Cytoplasmic Na+ binds to pump protein. P ATP K+ released ADP 6 K+ is released from the pump protein and Na+ sites are ready to bind Na+ again. The cycle repeats. 2 Binding of Na+ promotes phosphorylation of the protein by ATP. Na+ released K+ bound P Pi K+ 5 K+ binding triggers release of the phosphate. Pump protein returns to its original conformation. 3 Phosphorylation causes the protein to change shape, expelling Na+ to the outside. P 4 Extracellular K+ binds to pump protein. Figure 3.10
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Secondary Active Transport
Depends on an ion gradient created by primary active transport Energy stored in ionic gradients is used indirectly to drive transport of other solutes
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Secondary Active Transport
Cotransport—always transports more than one substance at a time Symport system: Two substances transported in same direction Antiport system: Two substances transported in opposite directions
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The ATP-driven Na+-K+ pump stores energy by creating a
Extracellular fluid Glucose Na+-glucose symport transporter loading glucose from ECF Na+-glucose symport transporter releasing glucose into the cytoplasm Na+-K+ pump Cytoplasm 1 The ATP-driven Na+-K+ pump stores energy by creating a steep concentration gradient for Na+ entry into the cell. 2 As Na+ diffuses back across the membrane through a membrane cotransporter protein, it drives glucose against its concentration gradient into the cell. (ECF = extracellular fluid) Figure 3.11
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The ATP-driven Na+-K+ pump stores energy by creating a
Extracellular fluid Na+-K+ pump Cytoplasm 1 The ATP-driven Na+-K+ pump stores energy by creating a steep concentration gradient for Na+ entry into the cell. Figure 3.11 step 1
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The ATP-driven Na+-K+ pump stores energy by creating a
Extracellular fluid Glucose Na+-glucose symport transporter loading glucose from ECF Na+-glucose symport transporter releasing glucose into the cytoplasm Na+-K+ pump Cytoplasm 1 The ATP-driven Na+-K+ pump stores energy by creating a steep concentration gradient for Na+ entry into the cell. 2 As Na+ diffuses back across the membrane through a membrane cotransporter protein, it drives glucose against its concentration gradient into the cell. (ECF = extracellular fluid) Figure 3.11 step 2
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Vesicular Transport Transport of large particles, macromolecules, and fluids across plasma membranes Requires cellular energy (e.g., ATP)
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Vesicular Transport Functions: Exocytosis—transport out of cell
Endocytosis—transport into cell Transcytosis—transport into, across, and then out of cell Substance (vesicular) trafficking—transport from one area or organelle in cell to another
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Endocytosis and Transcytosis
Involve formation of protein-coated vesicles Often receptor mediated, therefore very selective
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Coated pit ingests substance. Extracellular fluid Plasma membrane
1 Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm 2 Protein- coated vesicle detaches. Coat proteins detach and are recycled to plasma membrane. 3 Transport vesicle Endosome Uncoated endocytic vesicle 4 Uncoated vesicle fuses with a sorting vesicle called an endosome. Transport vesicle containing membrane components moves to the plasma membrane for recycling. 5 Lysosome 6 Fused vesicle may (a) fuse with lysosome for digestion of its contents, or (b) deliver its contents to the plasma membrane on the opposite side of the cell (transcytosis). (b) (a) Figure 3.12
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Coated pit ingests substance. Extracellular fluid Plasma membrane
1 Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm Figure 3.12 step 1
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Coated pit ingests substance. Extracellular fluid Plasma membrane
1 Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm 2 Protein- coated vesicle detaches. Figure 3.12 step 2
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Coated pit ingests substance. Extracellular fluid Plasma membrane
1 Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm 2 Protein- coated vesicle detaches. Coat proteins detach and are recycled to plasma membrane. 3 Figure 3.12 step 3
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Coated pit ingests substance. Extracellular fluid Plasma membrane
1 Coated pit ingests substance. Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm 2 Protein- coated vesicle detaches. 3 Coat proteins detach and are recycled to plasma membrane. Endosome Uncoated endocytic vesicle Uncoated vesicle fuses with a sorting vesicle called an endosome. 4 Figure 3.12 step 4
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Coated pit ingests substance. Extracellular fluid Plasma membrane
1 Coated pit ingests substance. Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm 2 Protein- coated vesicle detaches. Coat proteins detach and are recycled to plasma membrane. 3 Transport vesicle Endosome Uncoated endocytic vesicle 4 Uncoated vesicle fuses with a sorting vesicle called an endosome. Transport vesicle containing membrane components moves to the plasma membrane for recycling. 5 Figure 3.12 step 5
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Coated pit ingests substance. Extracellular fluid Plasma membrane
1 Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm 2 Protein- coated vesicle detaches. 3 Coat proteins detach and are recycled to plasma membrane. Transport vesicle Endosome Uncoated endocytic vesicle Uncoated vesicle fuses with a sorting vesicle called an endosome. 4 Transport vesicle containing membrane components moves to the plasma membrane for recycling. 5 Lysosome 6 Fused vesicle may (a) fuse with lysosome for digestion of its contents, or (b) deliver its contents to the plasma membrane on the opposite side of the cell (transcytosis). (b) (a) Figure 3.12 step 6
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Endocytosis Phagocytosis—pseudopods engulf solids and bring them into cell’s interior Macrophages and some white blood cells
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The cell engulfs a large particle by forming pro-
Phagocytosis The cell engulfs a large particle by forming pro- jecting pseudopods (“false feet”) around it and en- closing it within a membrane sac called a phagosome. The phagosome is combined with a lysosome. Undigested contents remain in the vesicle (now called a residual body) or are ejected by exocytosis. Vesicle may or may not be protein- coated but has receptors capable of binding to microorganisms or solid particles. Phagosome Figure 3.13a
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Endocytosis Fluid-phase endocytosis (pinocytosis)—plasma membrane infolds, bringing extracellular fluid and solutes into interior of the cell Nutrient absorption in the small intestine
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The cell “gulps” drops of extracellular fluid containing
(b) Pinocytosis The cell “gulps” drops of extracellular fluid containing solutes into tiny vesicles. No receptors are used, so the process is nonspecific. Most vesicles are protein-coated. Vesicle Figure 3.13b
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Endocytosis Receptor-mediated endocytosis—clathrin-coated pits provide main route for endocytosis and transcytosis Uptake of enzymes low-density lipoproteins, iron, and insulin
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Extracellular substances bind to specific receptor
Receptor-mediated endocytosis Extracellular substances bind to specific receptor proteins in regions of coated pits, enabling the cell to ingest and concentrate specific substances (ligands) in protein-coated vesicles. Ligands may simply be released inside the cell, or combined with a lysosome to digest contents. Receptors are recycled to the plasma membrane in vesicles. Vesicle Receptor recycled to plasma membrane Figure 3.13c
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Exocytosis Examples: Hormone secretion Neurotransmitter release
Mucus secretion Ejection of wastes
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The process of exocytosis The membrane- bound vesicle migrates to the
Plasma membrane SNARE (t-SNARE) The process of exocytosis Extracellular fluid Fusion pore formed Secretory vesicle The membrane- bound vesicle migrates to the plasma membrane. 1 Vesicle SNARE (v-SNARE) The vesicle and plasma membrane fuse and a pore opens up. 3 Molecule to be secreted Cytoplasm There, proteins at the vesicle surface (v-SNAREs) bind with t-SNAREs (plasma membrane proteins). 2 Vesicle contents are released to the cell exterior. 4 Fused v- and t-SNAREs Figure 3.14a
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Summary of Active Processes
Energy Source Example Primary active transport ATP Pumping of ions across membranes Secondary active transport Ion gradient Movement of polar or charged solutes across membranes Exocytosis Secretion of hormones and neurotransmitters Phagocytosis White blood cell phagocytosis Pinocytosis Absorption by intestinal cells Receptor-mediated endocytosis Hormone and cholesterol uptake Also see Table 3.2
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Membrane Potential Separation of oppositely charged particles (ions) across a membrane creates a membrane potential (potential energy measured as voltage) Resting membrane potential (RMP): Voltage measured in resting state in all cells Ranges from –50 to –100 mV in different cells Results from diffusion and active transport of ions (mainly K+)
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Generation and Maintenance of RMP
The Na+ -K+ pump continuously ejects Na+ from cell and carries K+ back in Some K+ continually diffuses down its concentration gradient out of cell through K+ leakage channels Membrane interior becomes negative (relative to exterior) because of large anions trapped inside cell
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Generation and Maintenance of RMP
Electrochemical gradient begins to attract K+ back into cell RMP is established at the point where the electrical gradient balances the K+ concentration gradient A steady state is maintained because the rate of active transport is equal to and depends on the rate of Na+ diffusion into cell
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1 2 3 K+ diffuse down their steep Extracellular fluid
concentration gradient (out of the cell) via leakage channels. Loss of K+ results in a negative charge on the inner plasma membrane face. 1 Extracellular fluid K+ also move into the cell because they are attracted to the negative charge established on the inner plasma membrane face. 2 A negative membrane potential (–90 mV) is established when the movement of K+ out of the cell equals K+ movement into the cell. At this point, the concentration gradient promoting K+ exit exactly opposes the electrical gradient for K+ entry. 3 Potassium leakage channels Protein anion (unable to follow K+ through the membrane) Cytoplasm Figure 3.15
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Cell-Environment Interactions
Involves glycoproteins and proteins of glycocalyx Cell adhesion molecules (CAMs) Membrane receptors
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Roles of Cell Adhesion Molecules
Anchor cells to extracellular matrix or to each other Assist in movement of cells past one another CAMs of blood vessel lining attract white blood cells to injured or infected areas Stimulate synthesis or degradation of adhesive membrane junctions Transmit intracellular signals to direct cell migration, proliferation, and specialization
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Roles of Membrane Receptors
Contact signaling—touching and recognition of cells; e.g., in normal development and immunity Chemical signaling—interaction between receptors and ligands (neurotransmitters, hormones and paracrines) to alter activity of cell proteins (e.g., enzymes or chemically gated ion channels) G protein–linked receptors—ligand binding activates a G protein, affecting an ion channel or enzyme or causing the release of an internal second messenger, such as cyclic AMP
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Cascade of cellular responses (metabolic and structural changes)
1 Ligand (1st messenger) binds to the receptor. 2 The activated receptor binds to a G protein and activates it. 3 Activated G protein activates (or inactivates) effector protein (e.g., an enzyme) by causing its shape to change. Extracellular fluid Effector protein (e.g., an enzyme) Ligand Receptor 4 Activated effector enzymes catalyze reactions that produce 2nd messengers in the cell Inactive 2nd messenger G protein GDP Active 2nd messenger 5 Second messengers activate other enzymes or ion channels 6 Activated kinase enzymes Kinase enzymes transfer phosphate groups from ATP to specific proteins and activate a series of other enzymes that trigger various cell responses. Cascade of cellular responses (metabolic and structural changes) Intracellular fluid Figure 3.16
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Figure 3.16 step 1 1 Ligand (1st messenger) binds to the receptor.
Extracellular fluid Ligand Receptor Intracellular fluid Figure 3.16 step 1
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Figure 3.16 step 2 1 Ligand (1st messenger) binds to the receptor. 2
The activated receptor binds to a G protein and activates it. Extracellular fluid Ligand Receptor G protein GDP Intracellular fluid Figure 3.16 step 2
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Figure 3.16 step 3 1 Ligand (1st messenger) binds to the receptor. 2
The activated receptor binds to a G protein and activates it. 3 Activated G protein activates (or inactivates) effector protein (e.g., an enzyme) by causing its shape to change. Extracellular fluid Effector protein (e.g., an enzyme) Ligand Receptor G protein GDP Intracellular fluid Figure 3.16 step 3
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Figure 3.16 step 4 1 Ligand (1st messenger) binds to the receptor. 2
The activated receptor binds to a G protein and activates it. 3 Activated G protein activates (or inactivates) effector protein (e.g., an enzyme) by causing its shape to change. Extracellular fluid Effector protein (e.g., an enzyme) Ligand Receptor 4 Activated effector enzymes catalyze reactions that produce 2nd messengers in the cell Inactive 2nd messenger G protein GDP Active 2nd messenger Intracellular fluid Figure 3.16 step 4
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Figure 3.16 step 5 1 Ligand (1st messenger) binds to the receptor. 2
The activated receptor binds to a G protein and activates it. 3 Activated G protein activates (or inactivates) effector protein (e.g., an enzyme) by causing its shape to change. Extracellular fluid Effector protein (e.g., an enzyme) Ligand Receptor 4 Activated effector enzymes catalyze reactions that produce 2nd messengers in the cell Inactive 2nd messenger G protein 5 GDP Active 2nd messenger Second messengers activate other enzymes or ion channels Activated kinase enzymes Intracellular fluid Figure 3.16 step 5
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Cascade of cellular responses (metabolic and structural changes)
1 Ligand (1st messenger) binds to the receptor. 2 The activated receptor binds to a G protein and activates it. 3 Activated G protein activates (or inactivates) effector protein (e.g., an enzyme) by causing its shape to change. Extracellular fluid Effector protein (e.g., an enzyme) Ligand Receptor 4 Activated effector enzymes catalyze reactions that produce 2nd messengers in the cell Inactive 2nd messenger G protein GDP Active 2nd messenger 5 Second messengers activate other enzymes or ion channels 6 Activated kinase enzymes Kinase enzymes transfer phosphate groups from ATP to specific proteins and activate a series of other enzymes that trigger various cell responses. Cascade of cellular responses (metabolic and structural changes) Intracellular fluid Figure 3.16 step 6
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