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Chapter Summary

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Chapter Summary

• All cells erect a lipid barrier (the plasma membrane ) to separate the inside of the cell from the outside, and then selec- tively modify the ionic composition in the intracellular environment to facilitate the biochemical reactions that sustain life. Intracellular fluid contains very low concentrations of Ca 2 compared with extracellular fluid . Na concentrations are also lower inside, but K levels are higher. • The plasma membrane contains three principal lipid types: phospholipids , cholesterol , and glycolipids . Phospholipids dominate the structure, cholesterol adds strength, and glycolipids mediate interactions with other cells. • Movement across membranes occurs primarily by diffusion . Diffusion rate is dependent on the transmembrane concen- tration difference , molecular size, membrane thickness and surface area, temperature, viscosity of the solution through which the molecule must diffuse, and the molecule’s solubility in lipid ( partition coefficient ). • Integral membrane proteins such as pores , channels , and carriers provide pathways by which hydrophilic molecules may cross the lipid barrier. • Pores are always open and are rare, the principal example being aquaporin , a ubiquitous water channel. Channels are regulated pores that open transiently to allow passage of small ions, such as Na , Ca 2 , K , and Cl . Movement through pores and channels occurs by simple diffusion down electrical and chemical concentration gradients ( electrochemical gradient ). • Carriers selectively bind ions and small organic solutes, carry them across the membrane, and then release them on the opposite side. Carriers operate by two modes of transport: facilitated diffusion and active transport . Facilitated diffusion moves solutes “downhill” in the direction of the electrochemical gradients (e.g., glucose transport by the GLUT transporter family). Active transport uses energy to move solutes “uphill” from an area containing low solute concentra- tion to an area of higher concentration. • Primary active transporters , or pumps , use adenosine triphosphate to drive solutes uphill against their electrochemi- cal gradient. Pumps include the Na -K ATPase that is present in all cells, Ca 2 ATPases, and the H -K ATPase. • Secondary active transporters move solutes uphill by harnessing the energy inherent in electrochemical gradients for other ions. Exchangers move two solutes across the membrane in opposite directions (e.g., the Na -Ca 2 exchanger). Cotransporters (e.g., Na -K -2Cl cotransporter and the Na -glucose cotransporter) move two or more solutes in the same direction. • The plasma membrane also contains receptor proteins that allow cells to communicate with each other using chemical messages. Signaling can occur over long distances via the release of hormones (e.g., insulin) into the bloodstream. Cells that are in close proximity to each other communicate using paracrines (e.g., nitric oxide). Autocrines are chemi- cal signals that target the same cell that released them. • Receptor binding is transduced in a variety of ways. Ligand-gated ion channels transduce binding using changes in membrane potential. Other receptor classes release G proteins to activate or inhibit second messenger pathways. Many receptors possess intrinsic kinase activity and signal occupancy through protein phosphorylation. A fourth class of receptor is located inside the cell. Intracellular receptors affect levels of gene expression when a message binds. • G proteins modulate two major second-messenger cascades. The first involves cyclic adenosine monophosphate ( cAMP ) formation by adenylyl cyclase . cAMP acts primarily through regulation of protein kinase A and protein phos- phorylation. • Other G proteins activate phospholipase C and cause the release of inositol trisphosphate ( IP 3 ) and diacylglycerol ( DAG ). IP 3 , in turn, initiates Ca 2 release from intracellular stores. Ca 2 then binds to calmodulin and activates Ca 2 - dependent transduction pathways. Ca 2 and DAG together activate protein kinase C and cause phosphorylation of target proteins. • Receptors with intrinsic tyrosine kinase activity autophosphorylate when the message binds. This allows them to com- plex with adapter proteins that initiate signal cascades affecting cell growth and differentiation. • Intracellular receptors translocate to the nucleus and bind to hormone response elements within the promoter region of target genes. Cell function is altered through increased levels of target gene expression.

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