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The working cell Energy in biology The nature of energy The molecule ATP and cellular work Enzymes biological catalysis The nature of catalysis How enzymes work The regulation of enzymes Functions of biomembranes Passive transport Osmosis and water balance Active transport Exocytosis and endocytosis Signaling Several movies today

Membrane Function Working cells must control the flow of materials to and from the environment. Membrane proteins are essential for this task. Membrane proteins perform a variety of functions. Copyright 2007 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Passive Transport: Diffusion Across Membranes Molecules contain heat energy They vibrate and wander randomly ( diffusion ) This eliminates concentration gradients Copyright 2007 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Passive transport is one example of diffusion across membranes Dynamic equilibrium: no net movement No energy is needed But selective permeability allows regulation of cell composition Examples: CO 2 and O 2 transport, H 2 O transport

Most substances that need to be transported into cells are hydrophilic (polar), but the inner parts of membranes are hydrophobic (non-polar) membranes are poorly permeable, simple diffusion across membranes is inefficient Simple diffusion Facilitated diffusion is the passive transport of hydrophilic substances by specific transport proteins that act as open doors in a selective manner Facilitated diffusion Movie facilitated diffusion 27 sec http://www.youtube.com/watch?v=s0p1ztrbxpy&feature=related

Facilitated diffusion can occur through channels or carriers Typically ions Are not saturable Typically small organic molecules like glucose Are saturable Movie Channels and carriers 29 sec http://www.youtube.com/watch?v=pq1pmbuviis&feature=related

Osmosis and Water Balance in Cells Osmosis: the passive transport (diffusion) of water across a selectively permeable membrane. Osmotic pressure Movie osmosis 48 sec http://www.youtube.com/watch?v=sdijtdrjqec&feature=related Copyright 2007 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Hypertonic solution Has a higher concentration of solute (= low concentration of water) Hypotonic solution ( 저장액 ) Has a lower concentration of solute (= high concentration of water) Isotonic solution ( 등장액 ) equal concentrations of solute 3:30 min http://www.youtube.com/watch?v=6mwl3dca2um

Survival of cells in different osmotic situations Red blood cell volume remains normal Cell gains water, swells, and may burst (lyse) if there is no wall Cell shrinks and may die from water loss Copyright 2007 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Osmoregulation in animals Terrestrial vertebrates use kidneys to regulate osmotic pressure Osmoregulation in plants Turgor (= back pressure from cell wall) is necessary for plant to retain upright posture In a hypotonic solution, a plant cell is turgid (firm) In an isotonic solution, a plant cell is flaccid (floppy), and a plant wilts

The passive transport of water A paradox: It was long assumed that water simply diffuses through the membrane, even though it was known that the membrane is hydrophobic We know now that water cannot easily diffuse through the membrane Specialized water channel proteins (aquaporins) in the plasma membrane allow the water to pass the membrane Aquaporin Video 39 sec http://www.youtube.com/watch?v=1uw6u0fznse Note the turn of the water molecule in yellow

Peter Agre, Noble Prize 2003, for the discovery of aquaporins

The level of one of the aquaporins was reduced by a genetic procedure Now the plant formed a larger root system to be able to take up sufficient water Normal plant Plant with reduced aquaporin level

Aquaporins are being used to develop a new water purification technology Traditional filtration technology Need high pressure High energy costs Aquaporin-based technology under development Pure water with low pressure Application: Desalination of sea water http://www.techamender.com/aquaporin-natures-clean-water-filter/

Active Transport: The Pumping of Individual Molecules Across Membranes Molecules move across the membrane against a concentration gradient. This requires energy Movie active transport 21 sec http://www.youtube.com/watch?v=stzoirqzzl4&feature=related Copyright 2007 Pearson Education, Inc. publishing as Pearson Benjamin Cummings

Our cells are batteries The enzyme Na + K + ATPase uses ATP to maintain a gradient of Na + and K + ions and an electrical membrane potential This enzyme consumes ~ 25% of all ATP in the resting body

Note that [K+] plus [Na+] inside the cell (152 mm) is larger than [K+] plus [Na+] outside the cell (149 mm) paradox? Solution: The Na+ K+ ATPase creates the primary electrical potential. The actual resting potential of the cell arises also from secondary movements of other ions

Primary (direct) active transport (for example Na/K ATPase) - solute accumulation is coupled directly to ATP hydrolysis (ATP ADP + Pi) Secondary (indirect) active transport - uphill transport of solute is coupled to downhill flow of a different solute

Overview of types of membrane transport of individual molecules = solutes

Exocytosis and Endocytosis: The mode of bulk transport through membranes (especially proteins and particles) Exocytosis Secretes substances outside of the cell. Copyright 2007 Pearson Education, Inc. publishing as Pearson Benjamin Cummings

Endocytosis Takes material into the cell. Movie exocytosis and endocytosis 36 sec http://www.youtube.com/watch?v=4gltk8yc1zc&feature=related Copyright 2007 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Types of endocytosis In phagocytosis ( cellular eating ), a cell engulfs a particle and packages it within a food vacuole. images.yahoo.com Movie (30 sec): White blood cell chases a bacterium and eats it: http://www.youtube.com/watch?v=fpoxgau5ffq&feature=related Movie (1 min 3 sec): Amoeba eats bacterium: http://www.youtube.com/watch?v=w6rnhimxtku&feature=related In pinocytosis ( cellular drinking ), a cell gulps droplets of fluid by tiny vesicles.

Receptor-mediated endocytosis Is triggered by the binding of external molecules to membrane proteins. LDL (low density lipoprotein: cholesterol) receptor Copyright 2007 Pearson Education Inc., publishing as Pearson Benjamin Cummings

The logic of transport through membranes Individual molecules or ions are usually sufficiently abundant to justify the construction (by evolution) of specialized transporter molecules (passive or active). Further, it is hard to imagine a selective bulk transport mechanism for small ions. Proteins are too diverse to justify the construction of a new transporter for each type of protein are transported in bulk, in buckets (membrane vesicles) Particles (especially bacteria) also require a membrane vesicle to be engulfed A specific situation arises for lipids. Lipids are insoluble transport in microdroplets (lipid particles). A receptor mechanism organizes the distribution of the lipid droplets to the different target cell types.

The Role of Membranes in Cell Signaling Cellular communication Begins with the reception of an extracellular signal. The signal transduction pathway Consists of proteins and other molecules that relay the signal. Copyright 2007 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Nice animation (8 minutes) showing various aspects of membrane function with the example of a white blood cell (leucocyte) invading a site of inflammation (Note: A cytokine is a hormone-like signaling substance that attracts the leukocyte) http://www.youtube.com/watch?v=gigxu1uxzxo

Summary Functions of biomembranes Biomembranes define, separate, and connect compartments (the cell itself and its organelles). The lipid bilayer, which is made of molecules with polar heads and hydrophobic tails, provides the ground structure of all biomembranes. The lipid bilayer is impermeable for hydrophilic substances (= water and water-soluble substances). Proteins that are embedded in the lipid bilayer specify most membrane functions such as transport, cellcell attachment, cell-matrix attachment, cell-cell recognition, signal perception, catalysis. Passive transport (based on diffusion, no energy expenditure). Channels (continuous, non-saturable passage of solutes, mainly ions and water itself) and carriers (valve-like, saturable passage, mainly of small organic molecules). Special case of water: Aquaporins (water channels) and osmosis (water diffusing through otherwise impermeable membrane separating two compartments with different concentrations of solutes). Active transport (against chemical or electrical gradients, energy is needed). Primary active transport (typically ion pumps) uses energy (e.g., ATP ) directly. Na+/K+ ATPase and others. Pumps maintain a membrane potential (cells are batteries). Secondary active transport (diffusion of an ion along gradient drives other substance to move against gradient). Exocytosis and Endocytosis. Bulk transport of fluid, proteins, or particles in buckets (= membrane vesicles). Special case: receptor-mediated endocytosis (e.g., directing uptake of lipids in form of lipoproteins). Phagocytosis refers to endocytosis of particles such as bacteria; may or may not involve receptors. The logic of transport through membranes. Transport proteins handle molecules individually. Transporters are constructed only for highly abundant or unusually important molecules. Proteins in general are too diverse to merit individual transporters.

요약 - 생체막의역할 생체막은부위를정의하고, 나누고, 그리고연결한다 ( 세포와세포소기관들 ). 소수성꼬리와극성의머리로구성된분자로이루어진, 지질이중막은모든생체막의기초구조이다. 지질이중막은친수성물질에비투과적이다 ( 물과물에녹는물질들 ). 지질이중막에박혀있는단백질은, 수송, 세포와세포간의부착, 세포와세포간충물질 (matrix) 간의부착, 세포와세포간의인식, 신호인식, 촉매등, 대부분의막기능을한다. 수동수송 ( 확산을기반으로함, 에너지소모없음 ). 통로 (Channel, 지속적, 용질의비포화적투과, 주로물과이온 ) 와운반체 (Carrier, 밸브와같음, 포화적투과, 주로작은유기분자들 ) 가있다. 물의특이한예 : Aquaporin ( 물통로 ) 와삼투현상 ( 농도가낮은곳에서높은곳으로선택적투과성막을통한물의확산 ) 이있다. 능동수송 ( 화학적또는전기적농도와반대로이동, 에너지가필요 ). 일차능동수송 ( 일반적으로이온펌프 ) 은직접에너지를사용한다 ( 예, ATP). Na+/K+ 펌프등 (Na+/K+ ATPase). 펌프는막전위를유지한다 ( 세포는건전지와같다 ). 이차능동수송 ( 농도기울기에의한이온의확산을이용하여, 농도와반대로다른물질을이동시킴 ). 세포외배출 (exocytosis) 와세포내유입 (endocytosis). " 용기 (= 소낭, membrane vesicle) 내유체, 단백질, 미립자의대규모수송. 특이한예 : 수용체매개세포내유입작용 ( 예, 지질단백질에서지질의직접적인흡수 ). 식균작용 (phagocytosis) 는세균과같은미립자의세포내유입작용을뜻한다 ; 수용체와관련이있기도없기도한다. 막을통한수송이론. 수송단백질은분자를각각다룬다. 수송단백질은, 오직양이많거나중요하고특이한분자들을위해서만만들어진다. 일반적으로단백질은그종류가다양하여, 각각의수송단백질을가지기어렵다.