General Physiology Lecture 1 PDF

DEPARTMENT OF FUNCTIONAL SCIENCES PHYSIOLOGY General Physiology Lecture 1 Physiology of the cell membrane: passive and active transport mechanisms 2023-2024 LECTURE TOPICS 1. Morphological and functional organization of the cell membrane 1.1. Memb...

DEPARTMENT OF FUNCTIONAL SCIENCES PHYSIOLOGY General Physiology Lecture 1 Physiology of the cell membrane: passive and active transport mechanisms 2023-2024 LECTURE TOPICS 1. Morphological and functional organization of the cell membrane 1.1. Membrane lipids. Structural and functional role 1.2. Membrane proteins. Functional and structural role 1.3. Specialized structures of the cell membrane 2. Transport functions of the cell membrane 2.1. Passive transport 2.1.1. Diffusion 2.1.2. Osmosis 2.1.3. Filtration 2.1.4. Ion channels 2.2. Active transport 2.2.1. Primary active transport 2.2.2. Secondary active transport 2 LEARNING OBJECTIVES Explain the organization and the role of the phospholipid matrix in the selective permeability of the cell membrane Discuss the classification criteria and the main functions of membrane proteins Describe the general classification criteria of membrane transport mechanisms Define the main characteristics of passive transport Describe passive transport by diffusion and osmosis List the factors that condition the rate of passive transport mechanisms Define and describe the general characteristics of passive transport through ion channels Describe the passive transport through voltage-gated and ligand-operated ion channels Define the main characteristics of active transport through cell membranes Describe the main types of ion pumps Discuss the differences between active and passive transport, and between primary and secondary active transport Describe the roles of the Na+/K+ pump, Ca2+ pump, H+/K+ pump and proton pumps Describe the operating mechanism and the roles of Na+/K+ pump Discuss the role of active transport mechanisms in generating gradients which maintain the passive transport Discuss about the importance of the active transport in transmembrane exchanges in the areas of epithelial exchange (digestive, renal) 3 LECTURE TOPICS 1. Morphological and functional organization of the cell membrane 1.1. Membrane lipids. Structural and functional role 1.2. Membrane proteins. Functional and structural role 1.3. Specialized structures of the cell membrane 2. Transport functions of the cell membrane 2.1. Passive transport 2.1.1. Diffusion 2.1.2. Osmosis 2.1.3. Filtration 2.1.4. Ion channels 2.2. Active transport 2.2.1. Primary active transport 2.2.2. Secondary active transport 4 GENERAL STRUCTURE OF THE CELL The main components of cells are: CELL MEMBRANE CYTOPLASM NUCLEUS 5 MORPHOLOGICAL AND FUNCTIONAL ORGANIZATION OF THE CELL MEMBRANE Cell membrane = plasmalemma Definition: lipoproteic molecular complex separating the cell from the extracellular environment Main function: barrier with selective and dynamic permeability, which controls the exchanges between the cell and the extracellular environment 6 MORPHOLOGICAL AND FUNCTIONAL ORGANIZATION OF THE CELL MEMBRANE Structure: fluid lipoprotein mosaic model (Singer, Nicolson, 1972) Lipids: phospholipids, cholesterol, glycolipids Proteins: peripheral, integral (transmembrane), glycoproteins Specialized membrane structures: microvilli, intercellular junctions 7 MEMBRANE LIPIDS: STRUCTURAL AND FUNCTIONAL ROLE PHOSPHOLIPIDS: form a phospholipid matrix composed of 2 monomolecular layers; each layer presents: a hydrophilic extremity towards the peripheral part of the membrane a hydrophobic extremity towards the middle part of the membrane  hydrophobic core which prevents free movement of substances CHOLESTEROL: on the inner part of phospholipid matrix provides flexibility and membrane stability contributes to selective characteristics of cellular membrane GLYCOLIPIDS: part of the cellular layer called glycocalix or pericellular atmosphere establish contacts with structures from extracellular environment 8 FUNCTIONS OF PHOSPHOLIPIDIC MATRIX 1. MEMBRANE SELECTIVE PERMEABILITY The membrane is: permeable for small liposoluble uncharged molecules: respiratory gases (O2, CO2) fatty acids glycerol steroid hormones urea ethanol impermeable for water-soluble substances: large uncharged molecules (glucose, amino acids) small charged molecules (ions) partially permeable to water 9 FUNCTIONS OF PHOSPHOLIPIDIC MATRIX 2. SOURCE OF INTRACELLULAR MESSENGERS Phosphatidyl inositol- 4,5 - biphosphate (PIP2) Membrane C phospholipase INTRACELLULAR MESSENGERS IP3 (Inositol triphosphate) DAG (diacylglycerol) IP3 stimulates Ca2+ release from endoplasmic reticulum  regulation of smooth muscle fiber contraction DAG activates membrane proteinkinase C  activation of intracellular enzymes regulating cellular metabolism and secretion 10 FUNCTIONS OF PHOSPHOLIPIDIC MATRIX 3. SOURCE OF EXTRACELLULAR MESSENGERS Membrane phospholipids Membrane A2 phospholipase ARACHIDONIC ACID Cyclooxygenase pathway Lipoxygenase pathway PROSTAGLANDINS (PG) THROMBOXANE (Tx) LEUKOTRIENES (LT) PGI2 (prostacyclin) TxA2 Vasodilation Vasoconstriction Inflammatory Inhibits platelets Stimulates platelets response adherence and adherence and Bronchial smooth aggregation aggregation muscle contraction 11 MEMBRANE PROTEINS: FUNCTIONAL AND STRUCTURAL ROLE Represent half of the membrane mass Represent the active element which induces the membrane properties and specific functions CLASSIFICATION depending on the relationship with the phospholipidic matrix: peripheral proteins (extrinsic) integral proteins (transmembrane, intrinsic) 12 MEMBRANE PROTEINS: FUNCTIONAL AND STRUCTURAL ROLE PERIPHERAL PROTEINS are poorly anchored to phospholipid matrix by electrostatic forces increased mobility in membrane plane Roles: mostly membrane enzymes: external: acetylcholinesterase (AChE) from post-synaptic membrane hydrolyses acetylcholine (ACh) into acetate and choline internal: adenylate cyclase (AC) generates cAMP (intracellular messenger) establish contacts with: cellular cytoskeleton  maintain cellular shape and are involved in cellular movements components of extracellular matrix  anchor the cell to extracellular structures 13 MEMBRANE PROTEINS: FUNCTIONAL AND STRUCTURAL ROLE INTEGRAL PROTEINS cross the entire matrix from one side to the other have asymmetrical structure, strongly glycosylated at the outer part strongly anchored to phospholipid matrix by covalent bounds reduced mobility in membrane plane Roles: channel proteins for ions and water transporter proteins (carrier) membrane receptors intercellular attachment intercellular recognition 14 SPECIALIZED STRUCTURES OF THE MEMBRANE DEFINITION: cytoplasmic elongations covered by plasmalemma 1. MICROVILLI = absorption increase the exchange surface (intestinal, renal epithelium) at the apical pole of the cells 2. CILIA = rhythmic movement capable of movement (”bend and wave”) but remain attached to a surface respiratory epithelium 3. FLAGELLA = transport propel the cell, “transporting” it somewhere sperm cells 4. INTERCELLULAR JUNCTIONS = contact contact between two cells are classified as: tight junctions anchoring junctions (desmosomes) gap junctions 15 SPECIALIZED STRUCTURES OF THE MEMBRANE TIGHT JUNCTIONS = impermeable junctions Roles of the mechanical barrier: protection: to prevent microorganisms from entering within blood through skin and mucosa functional: connect apical pole of epithelial cells prevent transport of water and other substances through intercellular space  epithelial permeability is inversely proportional with number of tight junctions block integral proteins movement between apical and basal surface of the cells, but allow receptor-mediated endocytosis (at the apical pole) and exocytosis (basal pole) 16 SPECIALIZED STRUCTURES OF THE MEMBRANE DESMOSOMES = anchorage provide contact between cells exposed to mechanical stress found in large number between epidermal cells and cardiac muscle fibers GAP JUNCTIONS = connexons allow bidirectional transfer of small molecules between 2 adjacent cells are excitable structures (electric synapses) allowing ion passage and excitation conduction found in large number between cardiac striated and smooth muscle fibers constitute some of the synapses within the central nervous system 17 SPECIALIZED STRUCTURES OF THE MEMBRANE 18 LECTURE TOPICS 1. Morphological and functional organization of the cell membrane 1.1. Membrane lipids. Structural and functional role 1.2. Membrane proteins. Functional and structural role 1.3. Specialized structures of the cell membrane 2. Transport functions of the cell membrane 2.1. Passive transport 2.1.1. Diffusion 2.1.2. Osmosis 2.1.3. Filtration 2.1.4. Ion channels 2.2. Active transport 2.2.1. Primary active transport 2.2.2. Secondary active transport 19 TRANSPORT FUNCTION OF THE CELL MEMBRANE DEFINITION: the process of crossing the cell membrane CLASSIFICATION depending on molecule size: micro transfer systems (micromolecules) macro transfer systems (macromolecules) - vesicular transport depending on energy consumption: passive transport Filtration active transport 20 PASSIVE TRANSPORT GENERAL CHARACTERISTICS: spontaneous without energy consumption (ATP) develops under the action of physical forces in the way of reducing some gradients: electrochemical potential osmotic pressure hydrostatic pressure MECHANISMS OF PASSIVE TRANSPORT Diffusion: Simple Facilitated Osmosis Filtration 21 DIFFUSION DEFINITION: transport of substances through a semipermeable membrane based on electrochemical gradient Chemical gradient: from higher concentration (C1) to lower concentration (C2) Electric gradient: ion diffusion towards the membrane side with opposite charge EXAMPLE: K+ through resting neuronal membrane Intracellular K+ concentration = 140 mEq/l, and extracellular K+ = 4 mEq/l  based on chemical gradient, K+ will diffuse from the interior to the exterior of the cell = K+ efflux Cellular membrane is positive on the outside and negative on the inside  based on electrical gradient K+ will diffuse from outside to the inside of the cells = K+ influx C2 K+ = 4 mEq/l Electric gradient Extracellular Intracellular K+ = 140 mEq/l Chemical gradient C1 22 DIFFUSION TRANSPORT MECHANISMS Simple diffusion through phospholipidic matrix: gas molecules (O2 and CO2) liposoluble molecules (urea, ethanol, steroid h.) water (smaller amount) Simple diffusion through ion channels: ion channels for Na+, K+, Ca2+ and Cl- Simple diffusion voltage-gated ligand-operated (gated) mechanically-operated water channels (aquaporin) ligand-operated Diffusion rate for simple diffusion depends on: membrane permeability dimension of electrochemical gradient size of exchange surface Diffusion through ion channels 23 DIFFUSION TRANSPORT MECHANISMS Facilitated diffusion: provides passive transport of organic uncharged substances (e.g. glucose, AA) requires a specific carrier protein increased transfer speed transport is limited to the maximum transporter capacity (Tmax) can be influences by biological active substances  insulin increases 10-20 times glucose facilitated diffusion by increasing the number of carrier proteins (GLUT) Diffusion rate for facilitated diffusion depends on: Dimension of electrochemical gradient Carrier capacity (Tmax value) 24 OSMOSIS DEFINITION: net diffusion of WATER from an osmotically active solution, through a semipermeable membrane, based on osmotic pressure gradient (Posm)  water passes from the side with lower Posm to the side with higher Posm Semipermeable membrane: permeable for solvent = WATER impermeable for solutes = osmotic active particles Osmotically active solution – contains solutes attracting water: NaCl Glucose Urea Proteins 25 OSMOSIS PARAMETERS: Osmotic concentration (Cosm) = number of osmotic active particles solved in unit of volume Plasma: 285 – 295 mOsm/l Osmotic pressure (Posm) = force opposing water passage (osmosis) through a semipermeable membrane. Posm gradient is determinant for direction and size of WATER transfer Plasma: 7.6 atm or 5776 mmHg Posm (atm) = Cosm x R x T Cosm = Osmol/L R = gases constant (0.082) T = solution temperature (K) 26 FILTRATION DEFINITION: represents water and micromolecular substances transport through permeable membranes, based on hydrostatic pressure gradient Hydrostatic pressure (Ph): pressure exerted by a fluid column on the exchange surface Ph gradient provides water and micromolecular substances transfer from the side with increased Ph to the side with lower Ph Ph =  x g x h ρ = fluid density g = gravity h = height of fluid column 27 MEMBRANE ION CHANNELS DEFINITION: integral proteins providing passive transport of ions down the electrochemical gradient CLASSIFICATION Based on channel dynamics: Leaky ion channels, providing continuous ion flow (e.g.: Na+ and K+ leaky channels) Gated ion channels, presenting transient molecular configurations equivalent to functional state (open/closed channel) (e.g.: Na+, K+, Ca2+, Cl- channels) Based on cellular localization: Plasma membrane channels (e.g., voltage-gated K+ channels) Intracellular channels, which are further classified into different organelles: endoplasmic reticulum channels (RyR, SERCA), mitochondrial channels (e.g., KATP) 28 MEMBRANE ION CHANNELS CLASSIFICATION Based on channel selectivity: Selective channels - for 1 ion (e.g.: Na+, K+, Ca2+, and Cl-) Partially selective channels - for 2 ions (e.g.: Ca2+/Na+, Na+/K+) Unselective channels – for 3 or more cations (e.g.: Na+, Ca2+, K+ cationic channels) Channel SELECTIVITY is conditioned by: ion charge ion size ion degree of hydration Based on factor conditioning channel dynamics: Voltage-gated channels Ligand-gated channels Mechanically-operated channels (stretch channels) 29 VOLTAGE-GATED ION CHANNELS CHANNEL DYNAMICS – determined by conformational changes induced to integral protein by transmembrane potential variation CHANNEL TYPES Fast Na+ channels K+ channels Slow Ca2+ channels Cl- channels STRUCTURE 1. Selectivity filter 2. Pore/passing channel 3. One/two gates 4. Voltage sensor 30 FAST Na+ CHANNELS DISTRIBUTION: neurons, skeletal muscle, myocardial fibers STRUCTURAL PARTICULARITIES strongly negatively charged  provide removal of H2O two gates: activation (m) and inactivation (h) FUNCTIONAL STATES resting channel - h gate open, m gate closed activated channel - both gates open inactivated channel - m gate open, h gate closed GATES DYNAMICS at the resting potential (-70 mV) they are in resting state reaching threshold potential (-55 mV) induces activation of Na+ channels  depolarizing Na+ influx (ascendant slope of action potential) at the peak (+30 mV) potential they inactivate condition membrane excitability Na+ channels activated or inactivated  unexcitable membrane Na+ channels in resting state  excitable membrane gNa+ = membrane conductance for Na+ gK+ = membrane conductance for K+ 31 K+ CHANNELS DISTRIBUTION: membrane of all excitable structures STRUCTURAL PARTICULARITIES not negatively charged one gate - n (activation gate) GATES DYNAMICS slower complete depolarization (+ 45 mV) induces activation of K+ channel  repolarizing K+ efflux (descending phase of action potential) gNa+ = membrane conductance for Na+ gK+ = membrane conductance for K+ 32 SLOW Ca2+ CHANNELS CHARACTERISTICS generally are partially selective (Ca2+ >> Na+) activated as a result of membrane depolarization induce Ca2+ influx involved in regulation of: cellular excitability muscle contraction cellular secretion CHANNEL type Distribution Role L (long lasting) Cardiac and smooth muscle Excitation/contraction coupling fiber T (transient) Pacemaker cardiac cells Cardiac automatism N (neuronal) Pre-synaptic neuronal Exocytosis of neurotransmitters membrane vesicles 33 Cl- CHANNELS CHARACTERISTICS found in striated muscle fibers opened as a result of membrane depolarization induce Cl- influx role stabilizing resting potential fine-tuning of cellular pH alter the ionic composition of the cytoplasm and volume of cells 34 LIGAND-GATED ION CHANNELS CHANNEL DYNAMICS - conformational changes of integral protein are induced under the action of a biological active substance named LIGAND: binds to a specific site at gate level can be neurotransmitter, hormone or intracellular messenger Closed channel CHANNEL TYPES operated by extracellular ligands operated by intracellular ligands operated by receptors through G proteins (G protein coupled receptors, GPCR) intercellular channels (connexons) Open channel 35 EXTRACELLULAR LIGAND-Gated channels CHARACTERISTICS: channel is part of post-synaptic membrane receptors structure, while the ligand is a chemical mediator CHANNEL Type Ligand Synapse Effect Na+ channels ACh Exciters of CNS and PNS depolarizing Na+ Motor end plate influx Cl- channels GABA CNS ihibitors hyperpolarizing Glycine Cl- influx Nonselective Glutamate CNS exciters depolarizing cation channels cationic influx (Ca2+, Na+, K+) CNS = central nervous system ACh = acetylcholine PNS = peripheral nervous system GABA = gamma amino butyric acid 36 INTRACELLULAR LIGAND-Gated channels CHARACTERISTICS located within the membrane of epithelial cells, and the ligand is an intracellular messenger (AMPc, Ca2+) located within the membrane of endoplasmic reticulum; the ligand is an intracellular messenger (IP3) CHANNEL Type Ligand Location Na+ channel cAMP Epithelial cells (nephrocyte, exocrine glands) K+ channel Ca2+ Myocardial fiber membranes Cl- channel Ca2+ Epithelial cells (exocrine glands, intestinal mucosa, and airways mucosa) Ca2+ channel IP3 Endoplasmic reticulum membrane Water channel cAMP Epithelial cells (nephrocyte, intestinal mucosa, and exocrine glands) 37 RECEPTORS-operated channels through G proteins CHARACTERISTICS - are Ca2+ or K+ channels that can become activated: directly - for K+ channel through β subunit of G protein indirectly - for Ca2+ channel through α subunit of G protein which activates membrane enzymes generating intracellular messengers: adenylate cyclase for cAMP guanylate cyclase for cGMP 38 Intercellular channels - CONNEXONS CHARACTERISTICS found at the level of permeable junction between two cells represent electrical synapses within cardiac and smooth muscle fibers are permeable for molecules with small diameter (water, electrolytes, intracellular messengers, metabolism end products) CONDUCTANCE SUPPRESSION is a mechanism for limitation of cellular lesion which induces: intracellular acidosis (pH) Ca2+ increase in one of the cell is triggered by simultaneous depolarization of both cells  unidirectional conduction of excitation 39 ACTIVE TRANSPORT CHARACTERISTICS develops against electrochemical gradient requires a specific transporter protein (carrier) requires energy consumption (ATP) dependent upon cellular metabolism and environmental conditions limited by Tmax (transport maximum), due to saturation of carriers can be competitive for chemically related substances, which have the same carrier (e.g.: amino acids) ROLES provides transport of organic molecules (glucose, amino acids) and most ions (Na+, K+, Ca2+, HPO42-, Fe2+, H+, etc.) enables concentration gradient (difference) of substances between intracellular and extracellular environment maintains mechanisms of passive transport CLASSIFICATION – based on ENERGY utilization: primary active transport = direct energy consumption secondary active transport = indirect energy consumption, by using the electrochemical gradient generated by primary active transport 40 PRIMARY ACTIVE TRANSPORT CHARACTERISTICS specific for ion transport transporter (carrier) protein is called ION PUMP (or ATPase) carrier protein is an ATPase ATP  ADP + Pi + E TYPES OF ION PUMPS Na+/K+ pump (Na+/K+- ATPase) H+/K+ pump (H+/K+- ATPase) Ca2+ pump (Ca2+ - ATPase) proton pump (H+- ATPase) Na+/K+ pump 41 ION PUMPS Are primary active transport specific for ion transport carrier protein is an ATPase General sequence of functioning comprises 3 main steps: 1. The ion binds on the membrane side with the lowest concentration of the ion 2. 1 ATP binds at the nucleotide binding, followed by hydrolysis ATP  ADP + Pi + E inorganic phosphate group (Pi) is used for increasing affinity of the pump towards the ion energy (E) is used for changing the conformation of carrier protein 3. The ion is released on the side with higher concentration nucleotide situs releases ATP hydrolysis products carrier protein conformation is restored to initial shape Ca2+ pump 42 GENERAL FUNCTIONS OF ION PUMPS Provide electrochemical gradient of substances  maintain membrane passive transport At the level of epithelial cells  support absorption/reabsorption at the digestive and renal exchange surfaces At the neuronal level  maintain and re-establish ion balance after depolarization (Na+/K+ pump) At the level of muscle fiber  enable muscle relaxation (Ca2+ pump) 43 Na+/K+ pump (Na+/K+ -ATPase) CHARACTERISTICS most important transport ATPase transports 3 Na+ outside and 2 K+ inside for 1 ATP increased energy consumption - 50% in neurons and nephrocytes, 10% in muscle fibers and hepatocytes STRUCTURE two α catalytic subunits on the inside: binding sites for 3 Na+ binding site for 1 ATP phosphorylation site for 1 Pi on the outside: binding sites for 2 K+ two β regulatory subunits translocation of pump from cytoplasm to membrane polarized distribution of pumps on the cell surface at the basal pole 44 Na+/K+ pump (Na+/K+ -ATPase) 45 Na+/K+ pump (Na+/K+ -ATPase) ROLES Electrogenic pump inducing electronegative charge on the interior of cellular membrane: maintains resting potential restores ionic balance after repolarization over-activate  mild hyperpolarization excessive inhibition  mild depolarization Provides Na+ gradient required for secondary active transport Involved in maintenance of cell volume (H2O follows Na+) REGULATION Activated by: insulin, thyroid hormones, catecholamines, increased cellular volume Inhibited by: ouabain (specific), cardiac glycosides (digoxin) 46 Ca2+ pump LOCATION – muscle fibers at the sarcolemma level – expels 2 Ca2+ in extracellular environment at la the SR level (SERCA, Sarco-Endoplasmic Reticulum Ca2+ ATPase) – recaptures 2 Ca2+ from cytoplasm ROLE: decrease of cytosolic Ca2+  muscle relaxation 47 H+/K+ pump LOCATION – membrane of parietal gastric cells and nephrocytes transports 1 K+ inside the cell in exchange for 1 H+ which exits the cell parietal gastric cell  formation of HCl in gastric lumen nephrocyte  urine acidification with important role in acid-base balance 48 H+ pumps LOCATION internal mitochondrial membrane  provides electrons transport during oxidative phosphorylation (ATP production) nephrocytes  urine acidification important for acid-base balance 49 SECONDARY ACTIVE TRANSPORT CHARACTERISTICS counter-gradient transport of an organic substance or ions transport coupled most frequently with Na+ transport develops down the Na+ electrochemical gradient, supported by Na+/K+ pump (energy consumption) LEGEND: G = glucose, AA = amino acids 50 SECONDARY ACTIVE TRANSPORT CLASIFICATION - depending on Na+ -coupled transfer direction CO-TRANSPORT – in the same direction with Na+ Na+/glucose co-transport  Na+ and glucose enter the cell Na+/amino acid co-transport  Na+ and amino acids enter the cell COUNTER TRANSPORT – opposite direction to Na+ Na+/H+ exchanger  Na+ enters the cell in exchange to H+ which exits the cell Na+/Ca2+ exchanger  3Na+ enter the cells in exchange to 1Ca2+ which exits the cell 51 SECONDARY ACTIVE TRANSPORT HCO3-/Cl- EXCHANGER – transfer depends on HCO3- concentration gradient created by carbonic anhydrase: CO2 + H2O  H2CO3  HCO3- + H+ Cells use energy provided by the H+ pump Cells endowed with carbonic anhydrase, HCO3-/Cl- and mechanism for H+ utilization are: Erythrocytes - role in acid-base balance HCO3- passes into blood in exchange with Cl- H+ is bound on erythrocyte buffer systems Parietal gastric cells - role in HCl secretion HCO3- passes into blood in exchange to Cl- H+ is secreted outside the cell and forms HCl Nephrocytes - role in acid-base balance HCO3- passes into blood in exchange to Cl- H+ is secreted in urine and is bound by urinary buffer systems 52 ENDOCYTOSIS AND EXOCYTOSIS ENDOCYTOSIS: material is engulfed within an infolding of the plasma membrane and then brought into the cell within a cytoplasmic vesicle once internalized, this new vesicle containing extracellular materials may fuse with a lysosome so that its solid contents are digested the resulting molecules may be released to the cytoplasm for use within the cell two general forms of endocytosis: phagocytosis = uptake of large solid particles such as bacteria or cellular debris pinocytosis = uptake of fluid and any small molecules dissolved within it receptor-mediated endocytosis = the particle first binds to a membrane protein receptor on the cell and the whole complex is engulfed EXOCYTOSIS (the reverse of endocytosis): an internal vesicle fuses with the cell membrane and releases its contents to the outside The balance of exocytosis and endocytosis preserves the size of the plasma membrane and keeps the cell’s size constant 53 MCQ Both simple and facilitated diffusion have which characteristics? A. Display saturation kinetics B. Require some type of carrier mechanism for transport C. Can work in the absence of adenosine triphosphate (ATP) D. Can transport material against concentration gradient E. Can be blocked by specific inhibitors In contrast to primary and secondary transport, diffusion does not require the input of additional energy, therefore, can work in the absence of ATP. Only facilitated diffusion displays saturation kinetics and involves a carrier protein. By definition, neither simple nor facilitated diffusion can move molecules from low to high concentration. The concept of specific inhibitors is not applicable to simple diffusion that occurs through a lipid bilayer without the aid of a protein. 54 TAKE HOME MESSAGES CELL MEMBRANE – lipid-protein molecular complex that delimits the cell from the extracellular environment, with a barrier function with selective and dynamic permeability, which controls the exchanges between the cell and the extracellular environment PASSIVE TRANSPORT ACTIVE TRANSPORT Spontaneous, without energy Requires energy consumption (ATP) consumption, under the action of physical Takes place against the electrochemical gradient forces Requires a specific transporter protein ("carrier") May require a carrier (facilitated diffusion) Takes place up to Tmax May take place up to Tmax (facilitated Depends on cell metabolism and environmental conditions diffusion) Can be competitive Reduces gradients - electrochemical Classification: potential, osmotic pressure, hydrostatic pressure primary active transport - direct energy consumption = ion pumps or ATPases Transporters for ions & water = channels secondary active transport - indirect energy Classification: diffusion, osmosis, filtration consumption – uses electrochemical gradient provided by the primary active transport = symporters and antiporters (exchangers) 55