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Chapter 3 Part B Cells: The Living Units © Annie Leibovitz/Contact Press Images © 2016 Pearson Education, Inc. PowerPoint® Lecture Slides prepared by Karen Dunbar Kareiva Ivy Tech Community College 3.4 Active Membrane Transport • Two major active membrane transport processes – Active transport – Vesicular transport • Both require ATP to move solutes across a plasma membrane for any of these reasons: – Solute is too large for channels, or – Solute is not lipid soluble, or – Solute is not able to move down concentration gradient © 2016 Pearson Education, Inc. Active Transport • Requires carrier proteins (solute pumps) – Bind specifically and reversibly with substance being moved – Some carriers transport more than one substance • Antiporters transport one substance into cell while transporting a different substance out of cell • Symporters transport two different substances in the same direction • Moves solutes against their concentration gradient (from low to high) – This requires energy (ATP) © 2016 Pearson Education, Inc. Active Transport (cont.) • Two types of active transport: – Primary active transport • Required energy comes directly from ATP hydrolysis – Secondary active transport • Required energy is obtained indirectly from ionic gradients created by primary active transport © 2016 Pearson Education, Inc. Active Transport (cont.) • Primary active transport – Energy from hydrolysis of ATP causes change in shape of transport protein – Shape change causes solutes (ions) bound to protein to be pumped across membrane – Example of pumps: calcium, hydrogen (proton), Na+-K+ pumps © 2016 Pearson Education, Inc. Active Transport (cont.) • Sodium-potassium pump – Most studied pump – Basically is an enzyme, called Na+-K+ ATPase, that pumps Na+ out of cell and K+ back into cell – Located in all plasma membranes, but especially active in excitable cells (nerves and muscles) © 2016 Pearson Education, Inc. Active Transport (cont.) • Leakage channels located in membranes result in leaking of Na+ into the cell and leaking of K+ out of cell – Both travel down their concentration gradients • Na+-K+ pump works as an antiporter that pumps Na+ out of cell and K+ back into cell against their concentration gradients • Maintains electrochemical gradients, which involve both concentration and electrical charge of ions – Essential for functions of muscle and nerve tissues © 2016 Pearson Education, Inc. Figure 3.1 Cell diversity. Erythrocytes Fibroblasts Skeletal muscle cell Smooth muscle cells Epithelial cells Cells that connect body parts, form linings, or transport gases Cells that move organs and body parts Macrophage Fat cell Cell that stores nutrients Nerve cell Cell that fights disease Sperm Cell of reproduction © 2016 Pearson Education, Inc. Cell that gathers information and controls body functions Focus Figure 3.1 Primary active transport is the process in which solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP. The action of the Na+-K+ pump is an important example of primary active transport. Extracellular fluid Na+ Na+ –K+ pump ATP ATP-binding site K+ Cytoplasm 1 Three cytoplasmic Na+ bind to pump protein. © 2016 Pearson Education, Inc. Slide 2 Focus Figure 3.1 Primary active transport is the process in which solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP. The action of the Na+-K+ pump is an important example of primary active transport. Extracellular fluid Na+ Na+ –K+ pump ATP ATP-binding site K+ Na+ bound Cytoplasm 1 Three cytoplasmic Na+ bind to pump protein. P ADP 2 Na+ binding promotes hydrolysis of ATP. The energy released during this reaction phosphorylates the pump. © 2016 Pearson Education, Inc. Slide 3 Focus Figure 3.1 Primary active transport is the process in which solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP. The action of the Na+-K+ pump is an important example of primary active transport. Extracellular fluid Na+ Na+ –K+ pump ATP ATP-binding site K+ Na+ bound Cytoplasm 1 Three cytoplasmic Na+ bind to pump protein. P ADP 2 Na+ binding promotes hydrolysis of ATP. The energy released during this reaction phosphorylates the pump. Na+ released P 3 Phosphorylation causes the pump to change shape, expelling Na+ to the outside. © 2016 Pearson Education, Inc. Slide 4 Focus Figure 3.1 Primary active transport is the process in which solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP. The action of the Na+-K+ pump is an important example of primary active transport. Extracellular fluid Na+ Na+ –K+ pump ATP ATP-binding site Na+ bound K+ Cytoplasm 1 Three cytoplasmic Na+ bind to pump protein. P ADP 2 Na+ binding promotes hydrolysis of ATP. The energy released during this reaction phosphorylates the pump. Na+ released P K+ 3 Phosphorylation causes the pump to change shape, expelling Na+ to the outside. P 4 Two extracellular K+ bind to pump. © 2016 Pearson Education, Inc. Slide 5 Focus Figure 3.1 Primary active transport is the process in which solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP. The action of the Na+-K+ pump is an important example of primary active transport. Extracellular fluid Na+ Na+ –K+ pump ATP ATP-binding site Na+ bound K+ Cytoplasm 1 Three cytoplasmic Na+ bind to pump protein. P ADP 2 Na+ binding promotes hydrolysis of ATP. The energy released during this reaction phosphorylates the pump. Na+ released K+ bound P Pi 5 K+ binding triggers release of the phosphate. The dephosphorylated pump resumes its original conformation. K+ 3 Phosphorylation causes the pump to change shape, expelling Na+ to the outside. P 4 Two extracellular K+ bind to pump. © 2016 Pearson Education, Inc. Slide 6 Focus Figure 3.1 Primary active transport is the process in which solutes are moved across cell membranes against electrochemical gradients using energy supplied directly by ATP. The action of the Na+-K+ pump is an important example of primary active transport. Extracellular fluid Na+ Na+ –K+ pump ATP ATP-binding site Na+ bound K+ Cytoplasm 1 Three cytoplasmic Na+ bind to pump protein. ATP P K+ released ADP 6 Pump protein binds ATP; releases K+ to the inside, and Na+ sites are ready to bind Na+ again. The cycle repeats. 2 Na+ binding promotes hydrolysis of ATP. The energy released during this reaction phosphorylates the pump. Na+ released K+ bound P Pi 5 K+ binding triggers release of the phosphate. The dephosphorylated pump resumes its original conformation. K+ 3 Phosphorylation causes the pump to change shape, expelling Na+ to the outside. P 4 Two extracellular K+ bind to pump. © 2016 Pearson Education, Inc. Slide 7 Active Transport (cont.) • Secondary active transport – Depends on ion gradient that was created by primary active transport system – Energy stored in gradients is used indirectly to drive transport of other solutes • Low Na+ concentration that is maintained inside cell by Na+-K+ pump strengthens sodium’s drive to want to enter cell • Na+ can drag other molecules with it as it flows into cell through carrier proteins (usually symporters) in membrane – Some sugars, amino acids, and ions are usually transported into cells via secondary active transport © 2016 Pearson Education, Inc. Slide 2 Figure 3.10 Secondary active transport is driven by the concentration gradient created by primary active transport. Extracellular fluid Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ K+ Na+-K+ pump ATP Cytoplasm 1 Primary active transport The ATP-driven Na+-K+ pump stores energy by creating a steep concentration gradient for Na+ entry into the cell. © 2016 Pearson Education, Inc. Na+ Na+ Slide 3 Figure 3.10 Secondary active transport is driven by the concentration gradient created by primary active transport. Extracellular fluid Na+ Na+ Na+-glucose Na+ Na+ Na+ Glucose Na+ Na+ Na+ K+ Na+-K+ pump symport transporter loads glucose from extracellular fluid Na+ Na+ Na+-glucose symport transporter releases glucose into the cytoplasm Na+ ATP Cytoplasm 1 Primary active transport Na+-K+ The ATP-driven pump stores energy by creating a steep concentration gradient for Na+ entry into the cell. © 2016 Pearson Education, Inc. 2 Secondary active transport As Na+ diffuses back across the membrane through a membrane cotransporter protein, it drives glucose against its concentration gradient into the cell. Vesicular Transport • Involves transport of large particles, macromolecules, and fluids across membrane in membranous sacs called vesicles • Requires cellular energy (usually ATP) © 2016 Pearson Education, Inc. Vesicular Transport (cont.) • Vesicular transport processes include: – Endocytosis: transport into cell • 3 different types of endocytosis: phagocytosis, pinocytosis, receptor-mediated endocytosis – Exocytosis: transport out of cell – Transcytosis: transport into, across, and then out of cell – Vesicular trafficking: transport from one area or organelle in cell to another © 2016 Pearson Education, Inc. Vesicular Transport (cont.) • Endocytosis – Involves formation of protein-coated vesicles – Usually involve receptors; therefore can be a very selective process • Substance being pulled in must be able to bind to its unique receptor – Some pathogens are capable of hijacking receptor for transport into cell – Once vesicle is pulled inside cell, it may: • Fuse with lysosome or • Undergo transcytosis © 2016 Pearson Education, Inc. Figure 3.11 Events of endocytosis mediated by protein-coated pits. 1 Coated pit ingests substance. Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm 2 Protein-coated vesicle detaches. 3 Coat proteins are recycled to plasma membrane. Transport vesicle Uncoated endocytic vesicle Endosome 4 Uncoated vesicle fuses with a sorting vesicle called an endosome. Lysosome 5 Transport vesicle containing membrane components moves to the plasma membrane for recycling. 6 Fused vesicle may (a) fuse (a) © 2016 Pearson Education, Inc. 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) Slide 2 Figure 3.11 Events of endocytosis mediated by protein-coated pits. 1 Coated pit ingests substance. Protein coat (typically clathrin) (a) © 2016 Pearson Education, Inc. Extracellular fluid Plasma membrane Cytoplasm (b) Slide 3 Figure 3.11 Events of endocytosis mediated by protein-coated pits. 1 Coated pit ingests substance. Protein coat (typically clathrin) Extracellular fluid Plasma membrane Cytoplasm 2 Protein-coated vesicle detaches. (a) © 2016 Pearson Education, Inc. (b) Slide 4 Figure 3.11 Events of endocytosis mediated by protein-coated pits. 1 Coated pit ingests substance. Protein coat (typically clathrin) Extracellular fluid Plasma membrane Cytoplasm 2 Protein-coated vesicle detaches. 3 Coat proteins are recycled to plasma membrane. (a) © 2016 Pearson Education, Inc. (b) Slide 5 Figure 3.11 Events of endocytosis mediated by protein-coated pits. 1 Coated pit ingests substance. Protein coat (typically clathrin) Extracellular fluid Plasma membrane Cytoplasm 2 Protein-coated vesicle detaches. 3 Coat proteins are recycled to plasma membrane. Uncoated endocytic vesicle Endosome 4 Uncoated vesicle fuses with a sorting vesicle called an endosome. (a) © 2016 Pearson Education, Inc. (b) Slide 6 Figure 3.11 Events of endocytosis mediated by protein-coated pits. 1 Coated pit ingests substance. Protein coat (typically clathrin) Extracellular fluid Plasma membrane Cytoplasm 2 Protein-coated vesicle detaches. 3 Coat proteins are recycled to plasma membrane. Transport vesicle Uncoated endocytic vesicle 4 Uncoated vesicle fuses with a sorting vesicle called an endosome. (a) © 2016 Pearson Education, Inc. Endosome 5 Transport vesicle containing membrane components moves to the plasma membrane for recycling. (b) Slide 7 Figure 3.11 Events of endocytosis mediated by protein-coated pits. 1 Coated pit ingests substance. Extracellular fluid Plasma membrane Protein coat (typically clathrin) Cytoplasm 2 Protein-coated vesicle detaches. 3 Coat proteins are recycled to plasma membrane. Transport vesicle Uncoated endocytic vesicle Endosome 4 Uncoated vesicle fuses with a sorting vesicle called an endosome. Lysosome 5 Transport vesicle containing membrane components moves to the plasma membrane for recycling. 6 Fused vesicle may (a) fuse (a) © 2016 Pearson Education, Inc. 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) Vesicular Transport (cont.) • Phagocytosis: type of endocytosis that is referred to as “cell eating” – Membrane projections called pseudopods form and flow around solid particles that are being engulfed, forming a vesicle which is pulled into cell – Formed vesicle is called a phagosome – Phagocytosis is used by macrophages and certain other white blood cells • Phagocytic cells move by amoeboid motion where cytoplasm flows into temporary extensions that allow cell to creep © 2016 Pearson Education, Inc. Figure 3.12a Comparison of three types of endocytosis. Receptors Phagosome © 2016 Pearson Education, Inc. Phagocytosis The cell engulfs a large particle by forming projecting pseudopods (“false feet”) around it and enclosing 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. Vesicular Transport (cont.) • Pinocytosis: type of endocytosis that is referred to as “cell drinking” or fluid-phase endocytosis – Plasma membrane infolds, bringing extracellular fluid and dissolved solutes inside cell • Fuses with endosome – Used by some cells to “sample” environment – Main way in which nutrient absorption occurs in the small intestine – Membrane components are recycled back to membrane © 2016 Pearson Education, Inc. Figure 3.12b Comparison of three types of endocytosis. Pinocytosis The cell “gulps” a drop of extracellular fluid containing solutes into tiny vesicles. No receptors are used, so the process is nonspecific. Most vesicles are protein-coated. Vesicle © 2016 Pearson Education, Inc. Vesicular Transport (cont.) • Receptor-mediated endocytosis involves endocytosis and transcytosis of specific molecules – Many cells have receptors embedded in clathrin-coated pits, which will be internalized along with the specific molecule bound • Examples: enzymes, low-density lipoproteins (LDL), iron, insulin, and, unfortunately, viruses, diphtheria, and cholera toxins may also be taken into a cell this way – Caveolae have smaller pits and different protein coat from clathrin, but still capture specific molecules (folic acid, tetanus toxin) and use transcytosis © 2016 Pearson Education, Inc. Figure 3.12c Comparison of three types of endocytosis. Vesicle © 2016 Pearson Education, Inc. Receptor-mediated endocytosis Extracellular substances bind to specific receptor proteins, 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. Exocytosis • Process where material is ejected from cell – Usually activated by cell-surface signals or changes in membrane voltage • Substance being ejected is enclosed in secretory vesicle • Protein on vesicle called v-SNARE finds and hooks up to target t-SNARE proteins on membrane – Docking process triggers exocytosis • Some substances exocytosed: hormones, neurotransmitters, mucus, cellular wastes © 2016 Pearson Education, Inc. Figure 3.13a Exocytosis. Extracellular fluid Secretory vesicle Plasma membrane SNARE (t-SNARE) Vesicle SNARE (v-SNARE) Molecule to be secreted Cytoplasm Fused v- and t-SNAREs The process of exocytosis 1 The membranebound vesicle migrates to the plasma membrane. 2 There, proteins at the vesicle surface (v-SNAREs) bind with t-SNAREs (plasma membrane proteins). Fusion pore formed 3 The vesicle and plasma membrane fuse and a pore opens up. 4 Vesicle contents are released to the cell exterior. © 2016 Pearson Education, Inc. Slide 2 Figure 3.13a Exocytosis. Extracellular fluid Secretory vesicle © 2016 Pearson Education, Inc. Plasma membrane SNARE (t-SNARE) Vesicle SNARE (v-SNARE) Molecule to be secreted Cytoplasm The process of exocytosis 1 The membranebound vesicle migrates to the plasma membrane. Slide 3 Figure 3.13a Exocytosis. Extracellular fluid Secretory vesicle Plasma membrane SNARE (t-SNARE) Vesicle SNARE (v-SNARE) Molecule to be secreted Cytoplasm Fused v- and t-SNAREs © 2016 Pearson Education, Inc. The process of exocytosis 1 The membranebound vesicle migrates to the plasma membrane. 2 There, proteins at the vesicle surface (v-SNAREs) bind with t-SNAREs (plasma membrane proteins). Slide 4 Figure 3.13a Exocytosis. Extracellular fluid Secretory vesicle Plasma membrane SNARE (t-SNARE) Vesicle SNARE (v-SNARE) Molecule to be secreted Cytoplasm Fused v- and t-SNAREs The process of exocytosis 1 The membranebound vesicle migrates to the plasma membrane. 2 There, proteins at the vesicle surface (v-SNAREs) bind with t-SNAREs (plasma membrane proteins). Fusion pore formed 3 The vesicle and plasma membrane fuse and a pore opens up. © 2016 Pearson Education, Inc. Slide 5 Figure 3.13a Exocytosis. Extracellular fluid Secretory vesicle Plasma membrane SNARE (t-SNARE) Vesicle SNARE (v-SNARE) Molecule to be secreted Cytoplasm Fused v- and t-SNAREs The process of exocytosis 1 The membranebound vesicle migrates to the plasma membrane. 2 There, proteins at the vesicle surface (v-SNAREs) bind with t-SNAREs (plasma membrane proteins). Fusion pore formed 3 The vesicle and plasma membrane fuse and a pore opens up. 4 Vesicle contents are released to the cell exterior. © 2016 Pearson Education, Inc. Figure 3.13b Exocytosis. Photomicrograph of a secretory vesicle releasing its contents by exocytosis (100,000) © 2016 Pearson Education, Inc. 3.5 Membrane Potential • Resting membrane potential (RMP) – Electrical potential energy produced by separation of oppositely charged particles across plasma membrane in all cells • Difference in electrical charge between two points is referred to as voltage • Cells that have a charge are said to be polarized – Voltage occurs only at membrane surface • Rest of cell and extracellular fluid are neutral • Membrane voltages range from –50 to –100 mV in different cells (negative sign (–) indicates inside of cell is more negative relative to outside of cell) © 2016 Pearson Education, Inc. K+ is Key Player in RMP • K+ diffuses out of cell through K+ leakage channels down its concentration gradient • Negatively charged proteins cannot leave – As a result cytoplasmic side of cell membrane becomes more negative • K+ is then pulled back by the more negative interior because of its electrical gradient • When drive for K+ to leave cell is balanced by its drive to stay, RMP is established – Most cells have an RMP around –90 mV • Electrochemical gradient of K+ sets RMP © 2016 Pearson Education, Inc. K+ is Key Player in RMP (cont.) • In many cells, Na+ also affects RMP – Na+ is also attracted to inside of cell because of negative charge • If Na+ enters cell, it can bring RMP up to –70 mV – Membrane is more permeable to K+ than Na+, so K+ primary influence on RMP • Cl– does not influence RMP because its concentration and electrical gradients are exactly balanced © 2016 Pearson Education, Inc. Figure 3.14 The key role of K+ in generating the resting membrane potential. Extracellular fluid Na+ K+ K+ + + + K+ A © 2016 Pearson Education, Inc. K+ K+ A Na+ Cytoplasm + because they are attracted to the negative charge established on the inner plasma membrane face. 3 A negative membrane potential K+ K+ concentration gradient (out of the cell) via leakage channels. Loss of K+ results in a negative charge on the inner plasma membrane face. 2 K+ also move into the cell + K+ K+ K+ + Potassium leakage channels K+ K+ Na+ CI + Na+ Na+ CI K+ Na+ Na+ Na+ K+ + Na+ 1 K+ diffuse down their steep Protein anion (unable to follow K+ through the membrane) (–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. Figure 3.14 The key role of K+ in generating the resting membrane potential. Extracellular fluid Na+ K+ K+ K+ + + + K+ + K+ K+ A A © 2016 Pearson Education, Inc. K+ K+ Na+ Cytoplasm + K+ K+ K+ + Potassium leakage channels K+ K+ Na+ CI + Na+ Na+ CI 1 K+ diffuse down their steep Na+ Na+ Na+ K+ + Na+ Slide 2 Protein anion (unable to follow K+ through the membrane) concentration gradient (out of the cell) via leakage channels. Loss of K+ results in a negative charge on the inner plasma membrane face. Figure 3.14 The key role of K+ in generating the resting membrane potential. Extracellular fluid Na+ K+ K+ K+ + + + K+ K+ A A © 2016 Pearson Education, Inc. + K+ K+ Na+ Cytoplasm K+ concentration gradient (out of the cell) via leakage channels. Loss of K+ results in a negative charge on the inner plasma membrane face. 2 K+ also move into the cell + K+ K+ K+ + Potassium leakage channels K+ K+ Na+ CI + Na+ Na+ CI 1 K+ diffuse down their steep Na+ Na+ Na+ K+ + Na+ Slide 3 Protein anion (unable to follow K+ through the membrane) because they are attracted to the negative charge established on the inner plasma membrane face. Figure 3.14 The key role of K+ in generating the resting membrane potential. Extracellular fluid Na+ K+ K+ K+ + + + K+ A © 2016 Pearson Education, Inc. K+ K+ A Na+ Cytoplasm + because they are attracted to the negative charge established on the inner plasma membrane face. 3 A negative membrane potential K+ K+ concentration gradient (out of the cell) via leakage channels. Loss of K+ results in a negative charge on the inner plasma membrane face. 2 K+ also move into the cell + K+ K+ K+ + Potassium leakage channels K+ K+ Na+ CI + Na+ Na+ CI 1 K+ diffuse down their steep Na+ Na+ Na+ K+ + Na+ Slide 4 Protein anion (unable to follow K+ through the membrane) (–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. Active Transport Maintains Electrochemical Gradients • RMP is maintained through action of the Na+-K+ pump, which continuously ejects 3Na+ out of cell and brings 2K+ back inside • Steady state is maintained because rate of active pumping of Na+ out of cell equals the rate of Na+ diffusion into cell • Neuron and muscle cells “upset” this steady state RMP by intentionally opening gated Na+ and K+ channels © 2016 Pearson Education, Inc. 3.6 Cell-Environment Interactions • Cells interact with their environment by responding directly to other cells, or indirectly to extracellular chemicals • Interactions always involves glycocalyx – Cell adhesion molecules (CAMs) – Plasma membrane receptors © 2016 Pearson Education, Inc. Role of Cell Adhesion Molecules (CAMs) • Every cell has thousands of sticky glycoprotein CAMs projecting from membrane • Functions: – Anchor cell to extracellular matrix or to each other – Assist in movement of cells past one another – Attract WBCs to injured or infected areas – Stimulate synthesis or degradation of adhesive membrane junctions (example: tight junctions) – Transmit intracellular signals to direct cell migration, proliferation, and specialization © 2016 Pearson Education, Inc. Roles of Plasma Membrane Receptors • Membrane receptor proteins serve as binding sites for several chemical signals – Contact signaling: cells that touch recognize each other by each cell’s unique surface membrane receptors • Used in normal development and immunity – Chemical signaling: interaction between receptors and ligands (chemical messengers) that cause changes in cellular activities • In some cells, binding triggers enzyme activation; in others, it opens chemically gated ion channels • Examples of ligands: neurotransmitters, hormones, and paracrines © 2016 Pearson Education, Inc. Roles of Plasma Membrane Receptors (cont.) – Chemical signaling (cont.): • Same ligand can cause different responses in different cells depending on chemical pathway that the receptor is part of • When ligand binds, receptor protein changes shape and thereby becomes activated • Some activated receptors become enzymes; others act to directly open or close ion gates, causing changes in excitability © 2016 Pearson Education, Inc. Roles of Plasma Membrane Receptors (cont.) – Chemical signaling (cont.): • Activated G protein–linked receptors indirectly cause cellular changes by activating G proteins, which in turn can affect ion channels, activate other enzymes, or cause release of internal second messenger chemicals such as cyclic AMP or calcium © 2016 Pearson Education, Inc. Focus Figure 3.2 G proteins act as middlemen or relays between extracellular first messengers and intracellular second messengers that cause responses within the cell. 2nd Ligand Receptor G protein Enzyme messenger (1st messenger) 1 Ligand*(1st messenger) binds to the receptor. The receptor changes shape and activates. 2 The activated receptor binds to a G protein and activates it. The G protein changes shape (turns “on”), causing it to release GDP and bind GTP (an energy source). 3 Activated G protein activates (or inactivates) an effector protein by causing its shape to change. Extracellular fluid Effector protein (e.g., an enzyme Ligand Receptor GTP GTP G protein GDP GTP 4 Activated effector enzymes catalyze reactions that produce 2nd messengers in the cell. (Common 2nd messengers include cyclic AMP and Ca2+.) Inactive 2nd messenger Active 2nd messenger 5 Second messengers activate other enzymes or ion channels. Cyclic AMP typically activates protein kinase enzymes. Activated Kinase enzymes * Ligands include hormones and neurotransmitters. © 2016 Pearson Education, Inc. Cascade of cellular Responses (The amplification effect is tremendous. Each enzyme catalyzes hundreds of reactions.) 6 Kinase enzymes activate other enzymes. Kinase enzymes transfer phosphate groups from ATP to specific proteins and activate a series of other enzymes that trigger various metabolic and structural changes in the cell. Intracellular fluid Focus Figure 3.2 G proteins act as middlemen or relays between extracellular first messengers and intracellular second messengers that cause responses within the cell. 2nd Ligand Receptor G protein Enzyme messenger (1st messenger) 1 Ligand*(1st messenger) binds to the receptor. The receptor changes shape and activates. Extracellular fluid Effector protein (e.g., an enzyme Ligand Receptor GTP GTP G protein GDP GTP Inactive 2nd messenger Active 2nd messenger Activated Kinase enzymes * Ligands include hormones and neurotransmitters. © 2016 Pearson Education, Inc. Cascade of cellular Responses (The amplification effect is tremendous. Each enzyme catalyzes hundreds of reactions.) Intracellular fluid Slide 2 Focus Figure 3.2 G proteins act as middlemen or relays between extracellular first messengers and intracellular second messengers that cause responses within the cell. 2nd Ligand Receptor G protein Enzyme messenger (1st messenger) 1 Ligand*(1st messenger) binds to the receptor. The receptor changes shape and activates. 2 The activated receptor binds to a G protein and activates it. The G protein changes shape (turns “on”), causing it to release GDP and bind GTP (an energy source). Extracellular fluid Effector protein (e.g., an enzyme Ligand Receptor GTP GTP G protein GDP GTP Inactive 2nd messenger Active 2nd messenger Activated Kinase enzymes * Ligands include hormones and neurotransmitters. © 2016 Pearson Education, Inc. Cascade of cellular Responses (The amplification effect is tremendous. Each enzyme catalyzes hundreds of reactions.) Intracellular fluid Slide 3 Focus Figure 3.2 G proteins act as middlemen or relays between extracellular first messengers and intracellular second messengers that cause responses within the cell. 2nd Ligand Receptor G protein Enzyme messenger (1st messenger) 1 Ligand*(1st messenger) binds to the receptor. The receptor changes shape and activates. 2 The activated receptor binds to a G protein and activates it. The G protein changes shape (turns “on”), causing it to release GDP and bind GTP (an energy source). 3 Activated G protein activates (or inactivates) an effector protein by causing its shape to change. Extracellular fluid Effector protein (e.g., an enzyme Ligand Receptor GTP GTP G protein GDP GTP Inactive 2nd messenger Active 2nd messenger Activated Kinase enzymes * Ligands include hormones and neurotransmitters. © 2016 Pearson Education, Inc. Cascade of cellular Responses (The amplification effect is tremendous. Each enzyme catalyzes hundreds of reactions.) Intracellular fluid Slide 4 Focus Figure 3.2 G proteins act as middlemen or relays between extracellular first messengers and intracellular second messengers that cause responses within the cell. 2nd Ligand Receptor G protein Enzyme messenger (1st messenger) 1 Ligand*(1st messenger) binds to the receptor. The receptor changes shape and activates. 2 The activated receptor binds to a G protein and activates it. The G protein changes shape (turns “on”), causing it to release GDP and bind GTP (an energy source). 3 Activated G protein activates (or inactivates) an effector protein by causing its shape to change. Extracellular fluid Effector protein (e.g., an enzyme Ligand Receptor GTP GTP G protein GDP GTP 4 Activated effector enzymes catalyze reactions that produce 2nd messengers in the cell. (Common 2nd messengers include cyclic AMP and Ca2+.) Inactive 2nd messenger Active 2nd messenger Activated Kinase enzymes * Ligands include hormones and neurotransmitters. © 2016 Pearson Education, Inc. Cascade of cellular Responses (The amplification effect is tremendous. Each enzyme catalyzes hundreds of reactions.) Intracellular fluid Slide 5 Focus Figure 3.2 G proteins act as middlemen or relays between extracellular first messengers and intracellular second messengers that cause responses within the cell. 2nd Ligand Receptor G protein Enzyme messenger (1st messenger) 1 Ligand*(1st messenger) binds to the receptor. The receptor changes shape and activates. 2 The activated receptor binds to a G protein and activates it. The G protein changes shape (turns “on”), causing it to release GDP and bind GTP (an energy source). 3 Activated G protein activates (or inactivates) an effector protein by causing its shape to change. Extracellular fluid Effector protein (e.g., an enzyme Ligand Receptor GTP GTP G protein GDP GTP 4 Activated effector enzymes catalyze reactions that produce 2nd messengers in the cell. (Common 2nd messengers include cyclic AMP and Ca2+.) Inactive 2nd messenger Active 2nd messenger 5 Second messengers activate other enzymes or ion channels. Cyclic AMP typically activates protein kinase enzymes. Activated Kinase enzymes * Ligands include hormones and neurotransmitters. © 2016 Pearson Education, Inc. Cascade of cellular Responses (The amplification effect is tremendous. Each enzyme catalyzes hundreds of reactions.) Intracellular fluid Slide 6 Focus Figure 3.2 G proteins act as middlemen or relays between extracellular first messengers and intracellular second messengers that cause responses within the cell. 2nd Ligand Receptor G protein Enzyme messenger (1st messenger) 1 Ligand*(1st messenger) binds to the receptor. The receptor changes shape and activates. 2 The activated receptor binds to a G protein and activates it. The G protein changes shape (turns “on”), causing it to release GDP and bind GTP (an energy source). 3 Activated G protein activates (or inactivates) an effector protein by causing its shape to change. Extracellular fluid Effector protein (e.g., an enzyme Ligand Receptor GTP GTP G protein GDP GTP 4 Activated effector enzymes catalyze reactions that produce 2nd messengers in the cell. (Common 2nd messengers include cyclic AMP and Ca2+.) Inactive 2nd messenger Active 2nd messenger 5 Second messengers activate other enzymes or ion channels. Cyclic AMP typically activates protein kinase enzymes. Activated Kinase enzymes * Ligands include hormones and neurotransmitters. © 2016 Pearson Education, Inc. Cascade of cellular Responses (The amplification effect is tremendous. Each enzyme catalyzes hundreds of reactions.) 6 Kinase enzymes activate other enzymes. Kinase enzymes transfer phosphate groups from ATP to specific proteins and activate a series of other enzymes that trigger various metabolic and structural changes in the cell. Intracellular fluid Slide 7