Cells Maintain Their Internal Environments Chapter 7 Cells Maintain Their Internal Environments

1 Transport proteins 2 Pumps, carriers, and nutrient distribution Cells, salts, and water balance 3

Cell Membrane Components of cell membrane Lipid: phospholipids, sterols Proteins : Receptor, adhesion proteins, recognition protein, transport protein Membrane-spanning domain Hydrophobic surface and hydrophilic core Transport of sugars, amino acids, ions Attachment to cytosolic or exterior face of membrane

Transport Across Membrane Diffusion Free diffusion by concentration gradient Hydrophobic substance, nonpolar molecules (O2, CO2), small polar molecules (water, ethanol) Transport proteins Channel proteins Transport of ions (Na+, K+, Ca2+, Cl-) along their concentration gradients Aquaporin: channel for water Gated channel Carrier proteins Escort metabolic building block along the concentration gradients

Simple Diffusion vs. Facillitated diffusion FIGURE 11-27 Energy changes accompanying passage of a hydrophilic solute through the lipid bilayer of a biological membrane. (a) In simple diffusion, removal of the hydration shell is highly endergonic, and the energy of activation (ΔG‡) for diffusion through the bilayer is very high. (b) A transporter protein reduces the ΔG‡ for transmembrane diffusion of the solute. It does this by forming noncovalent interactions with the dehydrated solute to replace the hydrogen bonding with water and by providing a hydrophilic transmembrane pathway.

Classification of Transporters FIGURE 11-28 Classification of transporters

FIGURE 11-25 Summary of transport types.

FIGURE 11-33 Three general classes of transport systems FIGURE 11-33 Three general classes of transport systems. Transporters differ in the number of solutes (substrates) transported and the direction in which each solute moves. Examples of all three types of transporters are discussed in the text. Note that this classification tells us nothing about whether these are energy-requiring (active transport) or energy-independent (passive transport) processes.

FIGURE 11-32 Chloride-bicarbonate exchanger of the erythrocyte membrane. This cotransport system allows the entry and exit of HCO3– without changing the membrane potential. Its role is to increase the CO2-carrying capacity of the blood.

FIGURE 11-34 Two types of active transport FIGURE 11-34 Two types of active transport. (a) In primary active transport, the energy released by ATP hydrolysis drives solute movement against an electrochemical gradient. (b) In secondary active transport, a gradient of ion X (often Na+) has been established by primary active transport. Movement of X down its electrochemical gradient now provides the energy to drive cotransport of a second solute (S) against its electrochemical gradient.

Transport Across Membrane Active Transport Pump Transport against concentration gradient high Na+ outside of cell, high K+ inside of cell Energy source ATP : e.g. Na+/K+ ATPase Concentration gradient of ions

ATPase in Animal cell FIGURE 11-38 Role of the Na+K+ ATPase in animal cells. In animal cells, this active transport system is primarily responsible for setting and maintaining the intracellular concentrations of Na+ and K+ and for generating the membrane potential. It does this by moving three Na+ out of the cell for every two K+ it moves in. The electrical potential across the plasma membrane is central to electrical signaling in neurons, and the gradient of Na+ is used to drive the uphill cotransport of solutes in many cell types.

Transport Proteins in Animals Nerve Impulses Resting membrane potential of -70mV (~EK=RT/ZFln[Kout]/[Kin] Opening of Na+ channel by stimulation Generation of action potential of 50 mV Opening of voltage-gated K+ channel Repolarization of membrane potential Restoration of membrane potential by Na+/K+ ATPase

ATP hydrolysis and synthesis are done by one enzyme FIGURE 11-40 Reversibility of F-type ATPases. An ATP-driven proton transporter also can catalyze ATP synthesis (red arrows) as protons flow down their electrochemical gradient. This is the central reaction in the processes of oxidative phosphorylation and photophosphorylation, both described in detail in Chapter 19.

Three states of the cystic fibrosis transmembrane conductance regulator, CFTR. BOX 11-3 FIGURE 1 Three states of the cystic fibrosis transmembrane conductance regulator, CFTR. The protein has two segments, each with six transmembrane helices, and three functionally significant domains extend from the cytoplasmic surface: NBD1 and NBD2 (green) are nucleotide-binding domains that bind ATP, and a regulatory domain (blue) is the site of phosphorylation by cAMP-dependent protein kinase. When this R domain is phosphorylated but no ATP is bound to the NBDs (left), the channel is closed. The binding of ATP opens the channel (middle) until the bound ATP is hydrolyzed. When the regulatory domain is unphosphorylated (right), it binds the NBD domains and prevents ATP binding and channel opening. The most commonly occurring mutation leading to CF is the deletion of Phe508 in the NBD1 domain (left). CFTR is a typical ABC transporter in all but two respects: most ABC transporters lack the regulatory domain, and CFTR acts as an ion channel (for Cl–), not as a typical transporter.

Transport Proteins in Animals Muscle contraction Action potential at the neuromuscular junction Opening of Ca2+ channel in the sarcoplasmic reticulum (SR: 근소포체) Released Ca2+ binding to troponin Movement of tropomyosin exposing myosin binding site

When Gradient Fail LongQT (LQT) syndrome Inherited heart failure Long recovery periods before new heart contraction Cell to cell variation of recovery periods Can cause arrhythmia (lack of rhythm) Defects in K+ or Na+ channels Inherited heart failure Mutation in the regulatory protein of Ca2+ channel in SR

Transport proteins 1 Pumps, carriers, and nutrient distribution 2 Cells, salts, and water balance 3

Pumps, Carriers, and Nutrient Distribution Epithelial cells Cells cover body surfaces and line internal organs Intestinal epithelium Microvilli facing the intestinal track Structure Tight junction between cell: prevent transport of large molecules Extra cellular matrix support epithelial cells

Transport of Nutrients across Epithelial Cells Intestinal side active transport of glucose powered by Na+ gradient Co-transport of Na+ and glucose Membrane side: carrier proteins

Glucose transport in intestinal epithelial cells: The Na+/K+ ATPase continues to pump Na+ outward to maintain the Na+ gradient that drives glucose uptake. FIGURE 11-44 Glucose transport in intestinal epithelial cells. Glucose is cotransported with Na+ across the apical plasma membrane into the epithelial cell. It moves through the cell to the basal surface, where it passes into the blood via GLUT2, a passive glucose uniporter. The Na+K+ ATPase continues to pump Na+ outward to maintain the Na+ gradient that drives glucose uptake.

1 Transport proteins Pumps, carriers, and nutrient distribution 2 Cells, salts, and water balance 3 3

Cells, Salts, and Water Balance Movement of water across the cell Water movement to equalize the total concentration of solutes Osmosis: movement of water across membranes Osmotic balance: A system with no net water movement Osmotic balance of cells Higher concentration of ions outside Cells contain many proteins, amino acids, and other small molecules to keep the osmotic balance

Cells, Salts, and Water Balance Water in human body (75 kg) 45 L total 30 L: intracellular 3.75 L: Blood plasma 11.25 L: extracellular fluid Importance of water balance for proper function of a body Lactose intolerance Lack of lactase breaking milk sugar lactose into glucose and galactose No digestion of lactose  movement of water into the intestine Metabolism of lactose by intestinal bacteria  gas production High-magnesium laxative : relieving constipation Cystic fibrosis Mutation in Cl- channel : reduced water secretion  thick mucus in epithelia of respiratory and gastrointestinal tracts Same solute

Biotechnology Rehydration therapy Diarrhea: kill 2 million children/year by dehydration Solution of sugar and salt is effective to treat dehydration: e.g. sports drinks Enzyme treatments for lactose intolerance Add lactase enzyme in milk or dairy products