Transport of Solutes and Water Hummingbirds are diatary specialists that feed aimost exclusively on flower nectors, which ‘re principally solutions of sucrose (lable sugar, plus other sugars, notably glucose and fructose, When sucrose itse is digested, it yields glucose and fructose. Thus a hummingbird has an abundance of glucose and fructose in its intestines after digesting a meal, and these simple sugars represent its immediate reward for feeding, The sugars, however, are in solution in the lumen—the hollow central core—of the intestines, and for them to do th bird any good, they must move into the bloodstream fo be cairied throughout the body. ‘You might at fistimagine that glucose and fructose in the lumen ofa hummingbirds intestines could simply diffuse across the intestinal epithelium into blood vessels. However, the hycrophil orhycrophobie nature of the molecules is a factor (ee Chapter 2). Glucose and fructose are hydrophilic, and because hydrophilic molecules tend not to mingle with hydrophobic or the sugars can be expected fo have difficully dissolving in the highly hydrophobic interior of the apical and basolateral cell membranes of the epithelial cells lining the intestine. In fact, the jucose and fructose from a: ciffuse into hummingbirds bloodsiream at significant rales. How then do the sugars move into the blood? Questions ofthis sort are among the most ‘common and important faced in the study of animal physio Mechanisms must exist to trarsport sugars from the ‘open central cavity of a hum mingbirc's intestines into its blood following a meal NNeclors are unusually rch in104 Chapter 5 (A) A single anima: cet: relative lon ‘concentrations inside and outside rrooesar ls io The size of teetering symoolize eave Jon concentrations nsiée and out the Cll Na’, Rand G~ ater subat-tilly 9 thai concerttations side and ouside (C) The epithelium ofthe smal intestine: glucose transport across the epithelium ‘Guicose and other naire molecules fom dgeste food must be transported across theintestnal epthaum to enter the bleed. Inthe lifeo“any anime’, many materials must move across cell membranesarl epithelia t substantial quantities to resupply cells or tissues witl needed raw materials, to void wastes, to maintain the proper composition of body fluids, and to otherwise maintain the animal's in-egrity. The solutes—thatis, the dissolved materi- als—that mave across cell tembranesand epithelia are chemically very diverse, and the mechanisms by which solutes and water eross are numerous. ~husa ques:-on that quickly arises is this: What term should be used tc describe the movements globally? In this book ‘we use the term transport to refer, in an entirely general way, to any and all movements of solutes or water across cell membranes ‘or epithelia, regardless of -2e mechanisms of movernent, ‘Three exarsples in whie> transport isimportant toaniteals will help define the subject of -nis chapter and provide a focus for our study of transgort. Here we describe -he examples. Later, as the chapter unfolcs, we will return toall three to elucidate the specific ‘transport processes involved 1. One of out fecal examoles s a single cell inside an animal's body. A typicel arima. cells bathed by extracellular fluid. ‘Thus we can :hink of -he cell membrane as separating an, intracellular fauid on the inside irom an extracellular fluid on the outside (FIGURE §.1A). The solutions on the inside and outside of 2 cell are ne=mally similar in their sum-total (©) The gil epithelium ofa freshwater fish: relative on ‘concentrations on the two sidas insT= me Wee en wo Ton concentration diferences aos ‘the gi eptholum are mpocant because unlike most body suriaces the af epthalum is prmeable toons. FIGURE 5.1 Three focal examples in which transport occurs Sludy ofthe three examples shown in this igure wl bring fo ight ‘most of the basic principles of solute iransport. (4) A typical cel in ‘an animat's body, surounded by extracellular uid. A" represents Cnionic (negatively charged) proteins and other solutes that can- not cross the cell membrane ond thus are rapped inside the cel. @)A freshwater fsh, showing representative on concentrations in ‘he blood plasma and surouncing pond water A thin epithelium is Ol that seporates the blood plasma and water in the gis ofthe fish (©) A diagram of the small intestine ofa bird or mommal, emphasiz Ing the intestinal epthelum ining the lumen. In realy the epi lium is miceoscopically thin. concentrations of dissolved matter; speaking more exactly, they have similar osmotic pressures.1 Consequently the solutions inside and outside a typical cell do not tend to exchange water in net fashion by osmosis to a great degree. However, the solufe compositions of the two solutions differ dramatically. The concentration of potassium ions (Ke) is much higher inside an animal cell than outside, for instance, whereas sodium (Na+) and chloride (C-) ions are typically less concentrated inside than outside. ‘These differences in solute composition suggest that the intracellular fluid ofa cell isnot at equilibrium with the extracellular fluid bathing the cell. What are the transport mechanisms by which ions such as Na+ and K+ move toward equilibrium across a cell membrane, and what are the transport processes that keep the intracelhular Fiuid different in composition from the extracellular fluid? 2. Our second focal example is the outer gill membrane of a {freshoater fish ling in a pond or stream. The fluid portion of the blood of a freshwater fish—known as the fish’s blood plasina—is much more concentrated in Nat, C-, and other inorganic ions than the surrounding pond or streain water is (FIGURE §.1B). In the fishs gills, the relatively T Osmotic pressures and osmosis ave discussed later in this chapter,concentrated blood plasma is separated from the dilute pond water by just a thin epithelium, Because the gill epithelium is a permeable rather than impenetrable barrier, the blood plasma tends to lose fons such as Na+ and Cl- to the pond water across the epithelium, and F120 tends to enter the blood plasma from the pond water across the epithelium. What are the transport mechanisms by which inorganic ions and H2O cross the gill epithelium? Are there transport mechanisms in the epithelium that help maintain the difference in composition between the fish's blood plasma and the environmental water? 3, Our third focal example is the intestinal epithe of the small intestine ofa bird or reammal. As we saw in Chapter 2 (Gee Figure 2.55), this epithelium consists ofa single layer of cells bearing microvilli on their apical cell membranes (FIGURE 5.1C). As stressed already in our discussion of hummingbirds, dissolved sugar molecules such as glucose and fructose must cross this epithelium from the intestinal lumen to the blood after a meal if they are to be of use to an animal. The same is true of dissolved amino acids and ‘other compounds. What a:e the transport mechanisms that move each of these materials across the epithelium? ‘As we start our study of transport mechanisms, an important organizing principle is the distinction between passive transport mechanisms and active ones. To define passive andl active in this context, we first need to define equilibrium, Be cautious ofthe term, because it is commonly used in nonscientific ways, such as when. people say that an angry child has “recovered his equilibriurn” or that a city has reached “equilibrium size.” These sorts of uses tend to confuse rather than clarify the scientific meaning ofthe term. ‘An accurate definition of equilibrium is based on the second law of thermodynamics, which describes the behavior of systems, termed isolated systems, that have no inputs or outputs of energy cr matter The second law of thermodynamics states that when an isolated system undergoes change, itis not able to change in all conceivable ways. Instead, an isolated system can change in only certain, limited ways, Equilibrium is, by definition, the state toward which an isolated system changes; thats isthe state toward which a system moves—internally—when it has no inputs or outputs of energy or matter. A system sat equlirium when internal changes ‘have brought it toan internally stable state from which further net change is impossible without system inputs or outputs, The state cof equilibrium isa state of rnin capacity to do work under locally prevailing condos. Thus a change toward equilibrium is always in the ditection of decreasing work potential Passive-transport mechanisms, by definition, are capable of carrying material only in the direction of equilibrium. Active- transport mechanisms, by contrast, cat carry material in the direction opposing equilibrium. The word can is emphasized for ‘an important reason: An active-transport mechanism does not necessarily carry materials inthe direction opposing equilibrium, but it is capable of doing so. Wesay much more about the second law of thermodynamics in Chapter > Appenuis J provides background on work and other physis concepts used inthis chapter Transport of Solurles and Water 105 ‘Giscose eituees in net fashion nthe ‘rection of fecuivium, whic iste direction ther equalzes ‘cercantation on tha two ede cf the membrane {A) Macroscople view of simple difusion Hoh glusose Dision of goose tonars eauilenum (8) Microscopic vow of simple aittusion ‘Asa l.cose meleaie on thee ‘sd af he memrane clices with ote moleculas, ts random motions, such as depicted here, fan linet up to passthrough 2 tet tha right sido ofthe ombrane. More moleces pass through the membrane rom left Hr ducoco torigt by ths chance proness than rom sight te et, senpiy is because the density of gucose I~ molecules i higher onthe sie a higher gece concertration. FIGURE 5.2 Simple diffusion viewed macroscopically and microscopically (A) A beaker is vides in half by © porous a= fifctal membrane that permits passage 2” glucose mclecules, bur nothing elee. The solutions on either cide c° the membrane cir in ‘lucase corcentration (symbolized by diferent cot densi). and ‘lveote atfuses through the membrane. 3) Looking ct the same system microscoploaty revoais that random motions cre more likely to carry glucose molecules from lett-o rt than fem rgh fo ll. A point fo stress is hat glucose ote cf the sor inthis example occur Cniy in arfcial membranes, notin king kiblagical membranes, Passive Solute Transport by Simple Diffusion ‘Simple diffusion is the most straightforward form =f passive sol- lute transpcrt. To understard simple d:tfusion, corsider a beaker divided by a nonliving membrane thet is penetrated by many rieroscopie pores through which the sugar glucose, but nothing else, can pass. A solution of glucose in waters placed on each side of the membrane, with the solution or the left having a higher glucose concentration than that on the ight. View.ng this beaker ‘macroscopically (FIGURE §.2A), we know ftom everyday experi- cence what will happen: Glucose will move in net fashion from left torightacross the membrane until ultimately the concentration of slucose is equal on both sides Howeves, what is the mecanim of ‘motion that carries glucose from left te right? In aédition, why do the concentrations of glucose on the twosides sry ual once zhey have become equal? ‘Answering these questions will reveal the natuze of simple diffusion, To answer them, we neec to cok at the 2eaker microssopi-106 Chapter 5 cally. At temperatures above absolute zero all atoms and molecules undergo ceaseless randox: motions. “magine that you're taking a nicroscopic look at the membrane aru the solution just on either side, and you fixyour eye cn e particular glucose molecule to the left cfthe membrane (FIGURE 5.26), This molecule, like all the others, ‘willbe moving constantly sometimes colliding with and bouncing cffother mole-ules ir rancam directions, There isa chance that one cfthese random motions ~ill carry the molecule through a pore in tne membrane to the rigt-hand side as the figure shows. Over a period of time, more gluccse molecules will move in this way from. left to right than froma rig-tto left, merely because there are more glucose molecales per un--of volume on the left. Macroscopically, these indivical molecular 2ven'swill-esultin net glucose transport from left to right. Once th concentrations on the two sides have become equa’, glucose mocecules will continue to move at random ‘om left to rigat and from right to left. The numbers of molecules going in the two directio=s will then be equal, however, because cf the equal rumbers of g:ucose molecules per unit of volume on tne two sides Thus, ata macroscopic level, the concentrations on the two sides will remain equal once -hey have become equal ‘The mechanism cf glucose transocct that we have just described is simple solute diffusior. Such diffasion is transport that arises om the molecular agitation that exists inall systems above absolute zero and from: the simple statistical tendency for such agitation to ‘arrymore motecules out cfregions of elatively high concentration tran into such regiors. Note that simple solute diffusion could not possibly increase the difference in glcose concentration between the two sides 3fa memibtace. The equilibrium state for the beaker in Figure 5.2is a state of cual glucose concentration on both sides, and simple sonte dif-usior. can change the glucose concentrations ccnly toward ecuilibrium, “hus simple solute diffusion is a passive tansport mecranism. ‘Simple diffusion is nos limited jus: to solutes in aqueous solu- ‘tons. Because molecular agi:ation is universal, simple diffusion is ‘universal: Cases diffuse in air; water dfuses even heat diffuses. AS ‘we now discuss the cuantita:ive principles ofthe simple diffusion cf solutes in acueous solutions, it is worth noting that all simple- ciffusion phe-omena fol-ow similar principles. Thus, later when ‘we discuss the quantitative laws of gas, water, and heat dicfusion,4 you will notice close simifer-ies tothe principles we now address. Finally, note that simple cffasion is often called just difiuson. Concentration gradients give rise to the most elementary form of simple solute diffusion Solutes diffe between any two regions ofa solution, whether or rotamembrare is presenc. To underscand the quantitative laws of solute diffusicn, we start with diffusica inam open solution, which {s the most general case. Consider a still open solution in which a solute, such as glucose, s at a relatively high concentration (C,) in one regicn and ata relatively low concentration (C,) in another. Imagine a representative I-sm cross-sectional area in the low concentration region fcieg toward the high-concentration region. ‘As solute malecutes diffuse into the lowv-concentration region from "Diffusion of gases is discussed n Chapter 22 (see page 388), Ditfasion of assed late: in this chapter, and that of walor vapor in 725), Diffusion of heat (heat conduction) iscovered in the high-concentration region, we can count the numbers of mol- ecules passing through this representative cross-sectional area per second. Specifically, we can count the net numbers that diffuse into the low-concentration region per second (the numbers diffusing in, minus the numbers diffusing out). Let /be the net rate of ciff- sion into the low-concentration region; that is, Js the net number of solute molecules passing into the low-concentration region per second through each unit of cross-sectional acea, Then en where Xisthe distance separating the negion oz high concentration (C) from the region of low concentration (C,). and D isa propor- tionality factor termed the diffusion coefficient. This formula- tion is often called the Fick aifusion equation, after Adolf Fick (1829-1900), who devised it. ‘The terms on the right-hand side of the Fick equation reveal important aspects of diffusion. Note that the rate (J) at which solute molecules diffuse into the low-concentration region is directly proportional to the difference in concentration (Cy ~ G). ‘Note also that the rate increases as the dlistance separating the two concentrations (X) decreases: Diffusion is a notoriously slow process for transporting substances from one place to anotherin the ‘macroscopic world, but when only a tiny distance separates regions ofdiffering concentration, diffusion can transport substances very’ rapidly. TABLE 6.1 illustrates this crucially important point. The table focuses on rates of diffusion wien there isa concentration difference ‘ofa small sohute between two regions ofa water solution. The table addresses the question: How much time is required for enough solute molecules to cross into the low-concentratior. region to reduce a concentration difference to half ofits starting magnitude? The time required is 32 years the distance between regions is 1 meter (m), but itis only 100 nanoseconds if the distance between regions is 10 nanometers (nrn)—the approximate thickness of acell membrane! The high rate of diffusion across minute distances helps explain ‘why diffusion is a crucially important process in the lives of cells. Tn the Fick equation, the ratio (C, -C,)/Xis called the concen {ration gradient, Itexpresseshow much the concentration changes per unitof distance. Note that, the diffusion rate, is proportional {o it, Sometimes the term concentration graientis used in a looser sense to refer only to the difference of concentration (C, - Cy) Foranalyzing complex solutions, an aspect af the concentration effects on diffusion that is worth emphasizing is this: The rate of diffusion of any particular solute is determined by the concentrations ‘of that solute, not the concentrations of other solutes that mightbe present. Exch solute diffuses according to its un concentration gradient, ‘What determines the diffusion coefficient D? One important factor is the ease with which the solute of intezest moves through the material separating the two concentrations; when diffusion is ‘occucting through a cell membrane or an epithelium, this factor is termed the permenbility of the membrane ct epithelium to the solute (we discuss permeability later in this chapter). Another factor that determines D is temperature, As ternperature rises, random ‘molecular motions become more vigorous (sez Chapter 10). Thus the rate of diffusion increases. Ifa fluid current flows over the surfaces cf an animal or cell, that flow can also affect the rate of diffusion. Suppose the con-pC Ann nce Mech om htc uals ay teria Bere aie caucioue ‘A biological dimension that exemplifies the distance specified Thickness of a cel membrane Radius of « small mammalian call Half-thickness of a frog sartorius muscle Hal-thickness of a human eye lens Thickness of the human heart muscle cau) 10 nanometers 10 micrometers 1 millimeter 2 milimeters 2 centimeters Length of a long human nerve cell 1 meter Pomel Nate ete cement eM ace ae eRe Cuan the time listed is the time required for diffusion to fransport half the solute molecules that must move ere ene tL an tee tae eee ee ean eo Distance between solutions Transport of Solutes and Water 107 Eisonecn cee nce Time required to halve a concentration difference y diffusion 7100 nanoseconcs 100 milliseconds 17 minutes 1.1 hours 46 doys 32 years ‘Source: Afer Weiss 1996, centration of a solute is 100 millimolar (mM) in the body fluids of ‘an aquatic animal and 2 mM in the ambient water. The outward diffusion of the solute will then tend to create a boundary layer of elevated solute concentration next to the animal's body surface (FIGURE 5.3). The presence of the boundary layer decreases the rate of diffusion, One way to understand this effect in terms of ‘Equation 5.1 is to consider the effect of the boundary layer on X, ‘which i the distance separating the two concentrations, 100 mM. and 2. mM withou: the boundary layer, these two concentrations ‘would be separated just by the thickness of the outer epithelium ‘of the animal, but with the boundary layer, the two concentrations ‘Dakar aaion fom the animal or call increases the concentration in the envrenmental solution rex othe autor aurface. The Bounds ayo" ts ‘rested may be very ti yt slave a substantal Impact onthe rate a fasion, 2M FIGURE 5.3 Diffusional concentration of a solute in a boundary layer next fo an animal or cell in this example. the ‘concentation ofthe solute is 100 mM inside the animal or cell and 2 mMin the open environmental solution. are also separated by the thickness of the boundary layer itself, ‘which increases X. Increasing the flow of weter over an animal or call tends to carry solute away from areas of accumulation a: the animal or coll surface, therety decreasin boundary-layer thickness. ‘This decreases X and therefore increases the ate f iffusive solute logs from the animal or cel. Electrical gradients often influence the diffusion of charged solutes at membranes ‘Many solutes of biological importance—such as Na“, CI and other inorganic ions—bear an electrical change. The diffusion of charged solutes—in addition to being affected by concentracicn gradients —i5, influenced by forces of electrical aitacton or repuisio. forces that do rotatfect the movement of urcharged solutes suck as glucose. As individual ions or other charged solutes move ceaselessly because ‘of atomic-molecular agitation, their pat”s of motion are affected by the attraction of positive charges toward negative cnes, and by the tendency of lke charges (e., two positive anes) tc repel ‘To understand wore such electrostatic “ects need to be con sidered in the analysis of dif“usion, a ker principle is that soluticns at largeare electrically neutral. In bulk sovution—e solution that is away from contact witha merbrane—the cor cen-ratons of positive and negative charges are always equal (AGURE 5.4). Thee? charge in any region of bulk solution is therefcre zero. Mozeover, because all regions of bulk solution have zero net charge, regions do not differ in net charge. This means that ir bulk soluti-n, the cherges on solutes do not affect their diffusior, and diffusion simply fol- lows the concentration-based principles we have clready discussed. In contrast to what hapens in bul solution. electrical at-rac- tion and repulsion can play large roles in diffusion along or across cell membranes or epithelia. This is true beceuse the lipid bilayers in cell membranes can maintain separction of opositely charged ions—meaning that different regions of solution cen differ in net electrical charge—by acting like capacitors in elerical circuits. 5 Appendix discusses capactence and othex physics concepts used in this chapter108 Chapter 5 FIGURE 5.4 lovic charge separation ‘occurs only within nanemeters of membranes Trus oniyir the viciniy of membranes do ccnditions exist forthe ot {fusion of charged solutes tc 20 attoctod by ‘seta attraction ond repulsion Win a few nanemeters ofthe membrane on iter sido, not postive and negative charge con= Centrabons may acum late because te pic Dilsyers in a eal mam- brane can maintain sep- aration of oppositely charged ions. Within a few nanometers of a cell membrane or epithelium, the solu-ion on onesie may have anet positve charge because positive ions outnumbe-negative ores. Conversely, within a few nanometers of the membrae or epithe um, the sol-tion on the other side may havea net negative charge necause negative ions outnumber posi- tive ones (see “gure 5.4). Under these circumstances the diffusion of electrically -rarged soles may be greatly affected by electrical axtrection and “epulsion. Biological aspects of diffusion across membranes: Some solutes dissolve in the membrane; others require channels Principles we discussed a: the start of Chapter 2 return to center stage when we censiderth2 chemical mechanismsof the diffusion of solutes through cell membranes or epithelia. The interior of a cell membrane is hycrophbic because it consists principally ofthe hydrocarbon tals of phoscholipid molecules composing the lipid bilayer (see Figure 2.1) The ease with which a solute can diffuse directly througa the lipid irterior ofa cell membrane thus depends toa the hydrophobic or hyc-ophilic nature of the solute. Let's start >y consideri- lipid sointes. such as steroid hormones and fatty acids, which are =ydrophobic. Molecules ofthese solutes ssclve in the ‘pid interic= ofa cell rembrane. In this dissolved state they make their way -om the sie othe membrane where they are more concent-aed tote sce where they are less concentrated bacause of molecular agitation and the other principles of simple diffusion we have been discussing. Mclecular axygen (0.3), which is small and ron2olar, is also generally believed to make its way throagh cell membranes p-imarily or xclusively by simple diffu- sion through te lipid layes, without the need of channels or other proteins, Certain signalirg molecules besides steroid hormones, such as thyroid lcrmones aed nitric axide, are also believed to cross cell membranes is this wer. organic ions present s very differert picture because they are hydrophilic and therefore have very low solubilities in membrane lipids. Studies using experimental ail-phospholipid membranes demonstrate =aat the rates of simple diffusion of ions directly thro.gh membrane lipids are exceedingly low. However, ions of paysiological importance—such as Na’, K’, Ca (calcium), and ‘Ch—can somerires mave zassively th-ough actual cell membranes at very rapid rates. They are abie to do this because their passive tract tid Feartor away, nO blk slution on ‘ther side, pesive and negative ons are rrixed at random. The et charge any given region of Bue Soliton z= transport through cell membranes takes place through integral ‘membrane proteins termed fo chanel. ‘The defining characteristic ofton channels that they permit the passive transport of inorganic ions by diffusion through a mem- brane. This means that the directions and eventual equilibrium states of the ion movements through channels are determined not by the channels themselves, but by the chemical-concentration and electrical-charge gradients that exist across a membrane. Another key characteristic of channelsis that the ions tha: pass through them, cdo not bind to the channel proteins. Structurally, an fon channel consists of one or more protein molecules that extend across the full thickness of a cell membrane or intracellular membrane and that encircle a lipid-free central passageway through the membrane (Gee Figures 24 and 13.16). From this fact and the fact that ions do not bind to channels, one might think that channels are simple holes through the membrane. Actually, they are intricate protein structures that are selective in determining which ions can pass readily through them.* Some ion channels, fr instance, are specific for Nat. They permit Na’ to move through the cell membrane ata relatively high rate but do not permit rapid passage of other ions. ‘Other channels are specific for K*, Still others allow Na’ and K*to ‘pass with equal ease. Some channels allow several sotts of fons to pass, but even the least selective channels discriminate between anionsand cations?” ‘Manion channelsare gated channels, meaning that they can “open’” and “close” because the proteins of which they are composed are able to undergo conformational change’ that cause theircentral passageways to increase or decrease the ease with which ions pass through (see Figure 12.20). Four categories of gated ion channels, distinguished by the mechanisms of gating, are recognized (FIG- URE 5.5). Vollage-gated channels open ancl close in response to changes in the voltage difference across a membrane; they are very important in the generation of nerve impulses. Sretch-gated (tension-gated) channels open or close in response to stretching (or pulling forces that alter the physical tensicn on a membrane, Phosphorylation-gated channels open or close according to ‘whether the channel proteinsare phosphorylated; such channelsare ‘under the control af protein kinases (Gee page 55), which are often ‘Teton selectivity of channels is discussed in detail in Chapter 12 7 Anions are negatively charged ions cations are positively charged ions(A) Voltage-gated channe! Exracallar id it Od gan bincing ofl FIGURE 5.5 Gated fon channels Gaiod ion channals are clas tiled info four functional cotegories based on which property must ‘change for them to open and close: (A) transmembrane voliags, 8) stretch of tension, (C) phosphorylation or (©) noncovatent binding with ligands at recepior sites themselves controlled by second messengers (Gee pages 66-67). ligand-gated channels, discussed in Chapter 2 (see page 63), act both as receptors of extracellular signals and as ion channels, ., They are closed to the passage of ions in the absence of a signal, but they open when their receptor sites bind to receptor-specific ligands (eg, neurotransmitter molecules), thereby allowing the passage of selected ions. Transpert of Sclutes and Water 109 ‘Thepermeabilty ofa cell membrane to a solute isdefined to be the ease with which the solve can neve through the membrane by diffusion. The concept of permeability apples bats to solutes that dissolve in the membrane inte-ior and fsoictes the: pass through channels. When Equation 5.1 i applies t2 sohute diffusion througha ‘membrane, the membrane permeability “>the solure interest helps determine D, the diffusion coefficient. Fer solutes, such aslipi'sand ,, that dissolve in the lipid b-layer to ass taroug’a membrane, the permeability of a cell membrane depends o” the factors that affect solute diffusion throcgt lipid, such as the molecular size of the solute, Forinorganic ions, the perneabil-y ofa el! membrane depends on the number of channels perunit of membrane area and (nthe proportion ofthe channels that re open. Call membranes are often described as selectively permeable because they permit some solutes to pass through >y diffusion with greater ease than others. One explanation for selective permeability that diferent sorts of ion channels are ofen unequally present. For example, if ‘a membrane hasa high density of Ne* erannelsan= a low density (of Ca’ channels, itis more permeabye = Nat than r0 Ca Diffusion of ions across cell membranes is determined by simultaneous concentration and electrical effects ‘The final aspect of the mechanism of simple cif“ision that we need to consider s the manne in whick concentration effects and clectrical effects interact in affecting the diffusion of ons and other charged solutes, We have already seen “hat, in animal cells, there {sa conceniration gradient across the cel- membrane for each major solute (ee Figure 5.1), The diffusion of each soiute is affected by its own concentration gradient but not by tae concentration gradients of other solutes. All cell mem3canes also exhibit charge separation. That is, there is always an electrica: gradient across accel membrane, defined to be the diffecence in voitage (electrical potential) between the two sides The electrical gradient affects the diffusion ofall changed so.utes. Itis obvious that the diffusion of en fon or other charged solute ‘must depend on both that solutes concentration gradient arid the electrical gradient. A problem :hat soor arisesin tre.ng to quantify this dual elfectis that concentration grodients and elecrical gradients are expressed in different units: moarty and volts, respectively. ‘Walther Nernst (1864-1941), an early winner of the Nobel Prize, ‘goes down in history for solving tis problem, Using his Nernst ‘equatior (discussed in Chapter 12) investigators fapresent cnionic solutes that canno” cross the ramiorane112. Chaoter 5 by Figure 5.8B. K* will be at electrockemical equilibrium, and no further net dizusion of K- will occur “Jpon rev:ewing this experimen:, you will see that when a merabrane is selectively permeable and blocks some solu:es from crossing, the diffusien of = permeating ion along its concentration gradient can create an electzical gradient. Thsis the sort of process that produces he voltage cifference, termes the membrane potential, thatty pial sxsts across he el merabrane ofan animaleell ee Figure 57) When a membrane is pe-meable to more than one sort of ion, an electrical aradiert preduced by diffusion of any one ion will affect the diffasion ofthe ethers because of electrical attraction and repulsion. A complex type o- e'ectrocemical equilibrium invalv- ing diffusion f rutiple iens (énd osmosis of water) then tends to develop. The Zonnan equilibrium, which you will see mentioned in advanced ‘ite-atue, is -his type of equilibrium. Specifically, a Donnan equi:brium occurs across a membrane when several ons {anions and cations) can cross the membrane but there isa set of norpermeaticg,-ons (ons that cannot cross the membrane) that are more abu-dant on or sie of the membrane than the other. Animal cellstend toward Donnan equilibrium because, relative to the axtracelluiar fluids batting therr, they have high concentrations of ronpermestiag aniorsc materials (e.g, proteins and nucleic within shem. SUMMARY Passive Solute Transport by Simple Diffusion IB Amectanism of sc ute ransoot is passive iit transports only foward electrochemical equilibrium. For an uncharged solute, re electrochemical equilibrium is the sarr2 as concentration equiliorium. For a charged soluto, fre oloctroc“emical equilioium is achieves. when tre valtege aference exactly counterbaiances the solute's concentration gradient across a coll membyene or epithelium, Simple -ggest consumers of ATP, using as much as 40% of the ATP a cell makes. ‘A great diversity of active-transport mechanisms is knewn. ‘Thus although any particalar active-cransport =echanis-n is specific for certain solutes, a great varie:y of solutes can be actively transported in one situation or another, including organic ions, amino acids, and sugars. “However, active-transpoctmecharisms seem not tohave evelved in animals for two of the mest impo:tant chemical substances in physiology: HO and O,,.Cucrent evidence indicates that H,C and (0, always move by passive rasport in arsmals114 Chapter § Stomach cay Prete callin esmach Tho praton pur H-K'-aTPase) that socotes omach aid protein that Isexpressedin parietal cals ‘Tho protein hydroyzes ATP te obtain ATP-Dona eneroy tecary out actve ion transport. ‘The pump exchanges two HM ortwo K" during each pumping eye tis thus Blectronat “Te apial membrane ofeach Paretal call projects nt the alas ivaginatons called Canali srguar carafe). ‘Te proton-pump protein molecules are postioned in the portions of the apical membrane tat ie the arabe eeara ecss SARA IENINE . FIGURE 5.9 Electroneutral active transport is responsible for secretion of stomach acid in the vertesrate stomach lining This acic-secreting paviefal cel s boundled fs cther-ypee of cols in the eptinallum lining the starnach. Anactive-transport mechanism that transports ions is poten- tally able toc-eete a voltage difference across a membrane because the mechanisma moves cha:ges. Active ion-transport mechanisms Co not necesscriiv generate voltage differences, however, because they often sirultancousl; transport -wo fons, and the transport cf two ions may 2¢ elect:cally neutral. For example, consider the ‘pump—inforrally knowr asthe proton pump—that in vertebrates isresponsibe ‘or-he extreme acidification of stomach contents. This proces: FIGURE 5.10 Summary of active and passive ion trarsport ina typical animal cell (A) The action of the No"-K° pumgin the ce “emorane. (B) Active ard pos Sve on anspe procasses, and related phenomena, in a cca Again, he sizeof the lefering inthe solutions symbol izes lative ior scnce "ations inside and oulside the cell The *eason thet Cis appicximately at electrochemical ‘equ librium is fat its concertration graient across the cell ‘membrane is a most exacth, opposed tr the voltage citer cence across the membrane 1A) The ection of the Na*-K~ pump ime —— SS oar aracaar Sue “The Net pure hryceoiyzes ATP, and t exchanges three Ne* ant I during each Pumping eyee, thus bere sectogeric, te normal charge diffrence stos he call membrane atsde postive) However mich of otthotype frembrane potential is discussed in detail in Chapter (8) An animal cet in summary Piola, wich colecivaly are arionc and symbolized A, are trapped inside the co. active-transport mechanism (FIGURES) simultaneously transports H* (protons) into the stomach cavity and K* inthe opposite direction in a 1: ratio. Mechanismssuch ast, which do not generate an imbalance of electrical charge, are termed electroneutral (nonelectrogenic) In contrast, an active-transport mechanism is electe genic if the actions of the mechanism create a charge imbalance across a membrane. Recognition of active transport completes our overview of a single animal cell At this point we can complete our discussion ofthe first of our three focal examples, the single animal cell (Gee Figure 5:14), We have seen that, in terms ofits Na” and K* concentrations, a cell is not at equilibrium with its surroundings. This nonequilibrium state is maintained bya ubiquitous, exceedingly important pump, the Na*= K* pump. During each cycle of pumping, this active transport mechanism transports three Na* ions out of cell and two K" fons in (FIGURE 6.104). Among other things, the pump is therefore electrogenic: Ithelps create ‘a charge difference across the cell membrane (outside positive) because it pumps more positive charges in one direction than the other:!? The Na*=K* pump is found in the basolateral membranes of all epithelial cells. Itisfound in all other sorts of animal cells as well. ‘pump, being electrogenic, contcbutes a portion ofthe Charge clifference originates from ion difusion empties in Figure 5. The generation of the Key —> Acie trareport > bitizon Boctrachamical ‘gradients favor steady ‘Sitsion of Na and K* through resting channels In tne ca membrane (CF is approximately atelectrochomical equllrium. The Na’-K* pump maintsns Nat and K* fons out of equléxium by Using ATP-bond enerEarlier (in discussing Figure 5.7) we concluded that acell must, transport Na* outward and K* inward, against electrochemical gradients, ifitis to maintain observed differences of ion composi- tion across the cel! membrane (between the intracellular and extracellular fluids). The Na*-K* pump carries out this transport using ATP-bond energy. FIGURE 6.10B surnmarizes the processes of both active and passive ion transport between an animal cell and the extracellular fluids that bathe it. Primary and secondary active transport differ in their cellularmolecular mechanisms Active-transport mechanisms are classified as primary or second- ary based on whether they use ATP directly or indirect. We will discuss primary mechanisms first. Doing so will st the stage for drawing rigorous distinction between the primary and second- ary types. One of the best-known transporter proteins engaged in active transport is Na*-K"-ATPase. This protein is the Na'-K* pump discussed a moment ago. The molecule is called an ATPase because itisan enzyme that catalyzes the hycrolysis of ATP as well asbeing, a transporter. This hydrolysis provides the energy that the protein uses for active Na*-K" transport. Na*-K*-ATPase belongs to a category of ATPases called P-type ATPases. This name refers to the fact that in these ATPases, the protein becomes phosphorylated and dephosphorylated during each pumping cycle. ‘The mechanism by which ATP-bond energy is transduced into ion motive energy by Na'-K'-ATPase—and by other P-type ‘ATPases—has been dramatically clarified inthe last 20 years and seems now to be largely understood. One key property is that these ATPases exhibit strict coupling between their molecular conformation and ATP hydrolysis: During each pumping cycle, the conformation of the transporter protein switches back and forth between two or more states, depending on whether the enzymatic hydrolysis of an ATP molecule has occurred. These conformation changes have two major effects on protein fune- tion. To understand these, we need to recognize that each molecule of a P-type ATPase has cntion-binding sites deep within its molecular structure. Transported ions bind to these sites as they pass through the transporter protein on their way from one side of the cell memnbrane to the other side. One major effect of the conformation changes that occur during a pumping cycle is to open passages between the eation-binding sites and the intra- and extrecelllar fluids. However, unlike a channel protein, there is, never an open passage all the way from the intracellular fluid to the extracellular fluid, Instead, as the molecular conformation undergoes change during a pumping cycle, at certain times a halé-channel opens between the cation-binding sites and the intracellular fluid ‘while the sites remain closed off from the extracellular fluid); and conversely, at other times a half-channel opens between the cation-binding sites and the extracelllar fluid (while the sites remain closed off from the intracellular fluid). ‘The second major effect of the conformation changes that occut duringa pumping cycle is that they dramatically modify the affinity af te caton-binding sits for specific ons. These affinity changes are # as dscussed on page 55, phosphor lation is covalent bonding toa orthophosphate group PO": Transpert of Sol.res and Water 115 synchronized with the opening and cl-sing of the half-channels to control which fons are bound ard which are expelled when ‘each half-channel is open. Let’s look at the action of Na*-K--ATPase to clarify these points. FIGURE 5.11 presents a model of one pumping cycle. At step @, the half-channel to the intracellalat Ziuidie open, ané the cation-binding sites have high affinity for Na* while having low affinity for K* Accordingly, Na* is taken up fron: the intracellular fluid, and K' is expelled into it. A mo‘eeale of ATP:s bound atthe ATPase catalytic site. Enzymatic hydrclysisof she ATP energizes the protein molecule and helps induce a corformaticn cnange tostate ‘© —in which three Na ions are occluded (ot of communication ‘with both intra- and extracellular fluids within the deep interior ‘of the protein. The energized protei: then changes -onformation to state @, in which the half-chanrel to the extracellular fluid opens and the cation-binding sites uncergo a dramatic reduction in their affinity for Na* and an increase in their aéfinity for K*, thereby expellingsNa' into the extracell_lar fluid anc taking up K°. Alo in state ®, an ATP molecule bincs to the protein at an ATP regulatory site, where itis not poised ‘or hydrclysis but inscead exerts modulatory effects, The state ofthe proteir. in © poises it to dephosphorylate, which leads to state @, in whica two K* fons are now occluded. The dephosporylation then leads to a return tostate @. As this occurs, the ATP molecule moves from the ATP regulatory site to the cataly:icsite and -nereby becomes poised to be hydrolyzed, energizing :he prote:n ance again, ‘The P-type ATPases include nct =nly Na*-K--ATPase but also Co*-ATPase, which is responsible for critical Ca®* pumping in the sarcoplasmic retic-um of muscle (¢ee Chapter 20), and Ht-K*-ATPase, the protor pump that acidifies stomach contents ‘Gee Figure 5.9). Al: the P-type ATPases are thought at present to function in closely simélar ways, Besides the P-type ATPeses, there are three other princpal categor.es of ATPases, known as Fetype, V-type, and ABC-type ATPeses, Primary dctive transports defined to be active transport that, draws energy immediately from the hycrolysis 0: A~P. Thatis. the ‘transporter protein in primary active transport isan ATPase. AS ‘you can see, the active transport ofNa* end K* by Na'-K*-ATPase is primary active transport. So alsc is the transport of Ca?” by Ca?*-ATPase, and that of protons by E*-K'-ATPace. Secondary active transport draws energy, in an immediate sense, not from ATP but from an elec:rochem‘cal gradient of a solute. ATP is required for secondary ective transport. However, ATP isnot the immediate source of energy tapoed 2y te transporter protein. Instead, ATP is ersployed to create an electrochemical gradient, which is employed by the trensporter protein to crive transport. Glucose absorption in the small irvestine of a hummingbird or other bird, or of a mammal, provides a classic examp-e of secondary active transport, Thus, to explore he principles of ‘secondary active transport and how energy is provided forit, we may now return to the focal example with which this chapter ‘opened, the case ofa hummingbird wh abuncan: glucose in its ‘Secondary active transports sometimes ca le indict ective transport, ‘ctve transpoct is sometimes celled die setive116 Chapter § on exracolar ach Cation-bincing sas dese win oes the molecule vary in thei ait Ne KATP age for Na" and" during tho stops false of a pumping cycle The dephospherfason tha: ee occured nb provous step Towers the atinty ofthe Oat ‘AIP is hyaroyaed. This caton-bidng ste for K* anc emoran ‘phosphorylates and energizes raises afiy for Ne Italo {no proton. The hal-oharnel Ineuces opening of the to the nacelle ud closes hatchannal tote trace Llar ‘la, ATP reves into tho ‘catalytic sts. posing it to be cop peer Irani fui catalytic sits “AOR On Ke onan The tein dephosprorylates. ‘This is stmuezed by 20th the binds 2° ATP tothe regulatory ste and the binding cf Ko the Cator-tnding sites. T> starts temeve fom the regclotory ste to the rear catalytic st Energy inated othe Phosphonyated roti bythe ‘ater ATP hycrlyss drives ‘pening of he al-channe! the extracel fui and ates the cation binding ses, ‘rasicalylowerng thal sty for Na* a raising tei airy Tork’ ATP binge to areguatory Ste, also stimulating hal-channol opening, ATP in ropdtory se FIGURE 5.11 Na*-K*-ATPase transduces ATP-bond energy into jon motive energy Show neve is 3 surrent model of fhe steps In.a.oumping cycle. Contto of the cyots is intrinsic, in the sense that the molecular stanges occuring at each step induce conformation ‘cnanges inet acd fo the ned step. Note hot there is never an open ‘crannel al the way between the extra: and intacaluia Nuigs: such a ‘crannel woule Sermit ions 9 cfuse “Soc«ward” and reduce the grad lens the pump is working fo oteate. Instead. hal:channels o the intr Cond extracellular fuids oper allemately (skates @ and @). with occlu- intestinal lamer after feed-g on nectar Specifically, let’ consider how glucose is tansported into a sirgle intestinal epithelial cell from the intestiaal lumen across the apical membrane of the cell (FIGURE 5.12) Recall tha: Na--K'~aTPase (the Na‘-K* pump) is found in the basolateral membranes of all epithelial cells. This Nat-K’-ATPase steadily transports Na* out of the intestinal epithelial cel: using ATP-bond ene-gy. This transport lowers the concentration of Na* :nsice the cell and thus creates a Na* sion patiods in belwsen (states @ and @).The pro-ein has two bincing sites for ATPATP fest bind to a regulatory sie where ithelps simulate conformation changes, nen moves info & cataiyic sila whore it hydrolyzed by the enzymatic activily of the protein. Bacause of the energy provided by ATP hyaraysis.ion movement can be against fhe electrochemical grodient. The protein is consiclered io have two major states, 1 and £2 In turn, each of those eon be phosphorylated (EP ‘and £2) or not. (Afer Bublz et al.2011,) electrochemical graclient across the cell’s asical membrane.!5 Because ofthe action of Na’-K*-ATPase, Na" is less concentrated Con the inside of the apical membrane than on the outside, andl in addition, the inside of the apical membrane is negative relative to the outside. As a result of bott of these preperties Gee Figure The electrochemical gradient is created across all parts of the cell membrane, bt we focus here onthe apical part bectuse is where glucose is transported int the cell fom the intestinal lumen(Gross sation of smatiiesine | ——e Tarsport against the secrochemea grades, (A) Na*-K"-ATPase in the basolateral membrane and the Na* ‘lectrochemical gradiont it generates across the apical membrane saree Tanspartin the reation of tha lostrechemiea! gracent Transport of Solutes and Water 117 ‘This protein facilcates the cbligntoriyfeked transport of Nat and glucose, The cotansporter Frotein does not use ATP and is not an ATFase. The zrotein, however, has the following essential tribute: =o- every twe Na* fons it carries across the membrane, it must, because ofits particular chemistry, ” oy ou Glu Possible Possible FIGURE 5.14 Two perspectives on epithelial active trans- ort (A) Wholeepiinelum and (8) cell membrane views of glucose fanspert across the eptinelum of the verlebxate small intestine. Each oint is to discuss the ealligative properties of aqueous solutions, because osmosis of water, discussec in the next section, is fundamenta:ly aeclligacve phenomenon, “he colligative prop- erties of aqueous solutions are the properties that depend simply ton the uber of dissolved entities per unit o: volume rather than, the chemical nature ofthe dissolved entities, TThe e a little less cbvious because ofthe way the properties are usually exprassed. Consider the freezing point and © fourth collgative propert> of occasional interes is the Bolling point, the lowest temperature et wal cause baling. aaa oct i ont Mie Ue Sonoty ures ua Sorc: etre Gu PO Na" we or s0/ Nat cr au e e e ee SE SaRe | | cases ° fa erties ° 2) e ee] Lea jst eo ee oe ‘e cate e sa Sau? FIGURE 5.16 Magnified views of two solutions that are sir lar in colligative properties Al the crewings depict identical volumes. The upper drawings of Solutions 1 and 2 show the chemical ature of each Gssolved entity in the solutions. The lower crowings of, the same fwo solutions show merely the numbers of cissolved eniiies within the volumes shown, csregarding chemical diierences. Be- ‘cause the two solutions have identical numbers af dssoked antes Por unit of volume, they are virtually the same in thei osmotic pros sures, reezing pois, ang other coligalive properties. Alb = albumin Glu = glucose, ‘water vapor pressure: When the concentration of dissolved entities in a solution is doubled, the factor that approximately doubles is the difference (ign ignored) between the actual freezing point or the actual water vapor pressure of the solution and the freezing point or the water vapor pressure of pure water. To see this more clearly, consider the reezing-point depression, defined tobe the Uifference (ign ignored) between the actual freezing point of a solution and the freezing point of pure water. The freezing-point «depression ofa solution is approximately proportional to the con- centration of dissolved entities, For example, ifthe freezing-point depression is .4°C before the concentration of dissolved entitiesis doubled, itis about 0.8°C after. This means that the freezing point itself lowered from—0.4°C to-0.8°C. The water-vapor-pressure depression is the difference (ign ignored) between a solution's ‘water vapor pressure and the waler vapor pressure of pure water under the same conditions. Itis approximately proportional to the concentration of dissolved entities. ‘Auseful corollary of the points already made is that the osmotic pressure, the freezing, point depression, and the water-vapor-pres- sure depression of a solution are all proportional to each other. This ‘means that if you have measured any one of these properties in a solution, you can calculate the others, a principle that we will see shortly has considerable practical significance. Only dissolved materials affect the coligative properties of solutions. Suspended materials, such as clay particles in river water or red blood cells in blood plasma, do not affect the osmotic pressures or the other coligative properties of solutions because they are not dissolved. Solutions of noneletroyies that are equal in their molar chemical concentrations typically are identical in their osmotic pressures and other colligative properties. This is easy to understand when you consider two principles: (1) a mole of solute always contains fixed number of molecules (Avogadro's number, 6 x 10°); and (2) when nonelectrolytes go into solution, each individual moleculeremains intact in the solvent, meaning that each constitutes a single dissolved entity, These two principles dictate that if several solutions of nonelectrolytes have equal molaities, they are also equal in their numbers of dissolved entities per unit of wolume. A 0.1-M solution of glucose, for example, has the same number of dissolved entities per unit of volume as a 0.1-M solution of urea. For the determination of colligative properties, it oes not mattet that the dissolved entities are glucose motecules in one solution and urea molecules in the other. Thus both solutions are virtually identical in their osmotic pressuresand other colligative properties, Similarly the coligative properties of a 0.1-M solution of a large, nondissociating protein such as serum albumin (molecular mass ~66,000 daltons [Dal) are essentially the same as those of the ‘equimolar solutions ofthe fower-mass solutes: 0.1-M glucose (180 Da) and 0.1-M urea (60 Da).” Solutions of electrolytes present additional complexities for predicting colligat-ve properties because individual molecules of electrolytes dissociate when placed in solution, giving rise to more than one dissolved entity. To take the simplest case, consider strong electrolytes, which dissociate fully when they are dissolved. When NaC a strong electrolyte, is dissolved, each molecule dissociates fully into two dissolved entities, a Na* ion and a Cl’ ion. This ‘means that a0.1-M solution of NaCl has twice as many dissolved entities per unit of volume as a 0.1-M glucose solution, Similarly, .0,-M solution of Na,SO, (sodium sulfate) has three times as many dissolved entities as a 0.1-M glucose solution, The colliga- tive properties of salt solutions exhibit nonideal behavior becau such solutions do not behave exactly as if each dissociated ion is ‘an independent dissolved entity. In most situations relevant to animal physiology, however, a relatively close approximation to {deal behavior is o2served. From the viewpoint of ideal behavior, for example, we would expect a 0.1-M solution of NaCl to have an ‘osmotic pressure and freezing-point depression that are 2 times higher than those ofa 0.1-M glucose solution. The actual osmotic pressure and freezing: point depression are about 19 times higher in the NaCl solution, Physiologists usually express osmotic pressure in osmolar units ‘The most commonly used system of units for osmotic pressure in biology todey is the osmolarity system, A T-osmolar (Osm) solution is defined to be one that behaves osmotically as if t has 1 Avogadro's number of independent dissolved entities pet liter. Saying the same thing in another way, a 1-Osm solution has the same osmotic pressure as is exhibited by a 1-M solution of ideal nonelectrolyte. Some solutions relevant to animal physiology, such as seawater and the bloods of most marine invertebrates, ate concentrated enough to be about Osm. Many solutionsin animal physiology, however, ae more dilute and their osmotic pressures ate typically expressed in units of miliosmolarity; a T-millosmolar (mOsm) solution behaves osmotically asifit has 0,001 Avogadro's number of independent dissolved entities per iter. ‘To be sirilly accurate, solutions of various nonelectroytes have the same ratio of dissalved entities to water molecules when they are of the ‘Same molality, not molarity Thus Is solutions of identical molality that ‘exhibit dential colizative properties Biologists usually measure and ‘iscuss molaetes, and for most purposes this habit dos not introduce ‘consequential errors Transport of Solutes and water 123 Osmotic pressures can be measured in several ways Forday-to-day prac‘cal purposes in phy sology and medicine tnday, people measure osmotic pressures by employing instruments that actually measure e-her the freezing: pint depression or the water- ‘vapor-pressure depression. These are ca ed fewing-painl oxmometers ancloupor-presstreosmoneters. Theinstr- nents take a-lvantage ofthe point, stressed eartir, thatall the colligaive properties ofa solution are typically proportional to each other. Thus the osmotic pressure can be calculated a‘ter the freezing-po-nt depressioa or the water- vvapor- pressure depression has been measured.” Physical chemistshave devised me-nods of meacuiring osmotic pressure itself, rather than calculatingit ‘rom other cclligative prop- erties. These methods are the gold stexdard of osmotic-pressure measurement, but usually they are no- employed ‘or day-to-day practical work by biologists because they are c-mbersome to carry out. FIGURE 5.17 illustrates the Fasc approzch to the cirect measurement of the osmotic pressure cf a solution. The solution is 2 Prior o about 1980, # was common for biologists who messured fe point depression to lesve their results in temearature unis ther than Srvertng them o omar Thus in the lvratuce ofthat ora you wil find ‘osmotic presses expressed in dogrees Celsus! The equivaveney is tha a Ireezing!point depression of LBS°C conesponds to 1 Os ng (A) A plston device for cirect measurement of osmotic pressure ‘Serypereie memerene Soliton “The solution tke reared is soparstad ‘rom pure water by @ semparmeable mem bree (a memarane pornestie on 10 ‘wate that forms the ene af an iced, fetioriess piston procure that exactly opposes osmosis, <—$ camate wetormeremert > Water movement cause by hycrstte press FIGURE 5.17 How "0 measure the osmotic pressure of a solu tion directly (A) A piston osmometor. 8) Alter ste ofthe system ifthe piston is foe fc move. Water rraves nfo the solultan by osmosis (©The stable state of he syrem i the sclution is subjected fo in- creased hydrostatic pressure by « force applied fo the pision and the diference of hydrostatic pressuie across the membicre is equa fo the ‘osmotic pressure of the solution. The open sidearm o- the pure-water ‘compartment in (C; pernts the hysrostatic pressure that compart ‘men! fo remain constant as the hyckostatic pressure r the solution ‘compartment is increased.124 Chapter 5 FIGURE 5.18 Predicting the direction of osmosis between two so utions from measurements made independently on each Tre red artows ir the two rane—provide avenues for water molecules to move by esmosis trough she cell membrane without encourter.ng the lip ilayers. The mos-important of these water-channel proteins, which speed osmosis, ae the aquaporins, Aquaporins ‘The aquaporins (‘water pores") are alarge family of water-channel proteins founc :n all grouss of organisms. Although extremely Impostant, they were disccered oniy in 1992. Prior to that date, rystery shrouded many 0” the processes and illnesses in which the aquaporins pley roles, ‘The aquapctins are in general remarkably specific to H,O. For example, althougl. they allow HO to pass through, they do not allow hydronitn ions (H,0") to pass. The study of aquaporins is an exploding azea of research. Thirteen molecular forms of aquaporins—: osmosis? 3. Consider three groups 0 salutes: (steroid hormones, fatty acs, and other isis (inorganic ons ard i) polar organic solutes such a glucose and amice acids Whats the principal mechanazn byywhich each aroup erossseall membranes passively? Why do members of-he firs group cross ina fundamentally different way from solutes belonging the other two groups? 4. (9 Lietheatesing darn as ackngy commen problem Inthe devel ping word Fsope wih hie Iveateningdnrthen often Na? depleted, ard save tei lives epatng Nai sso, However, Tan” Nain theese raced Drinking asa.ton of NaCl dows not therefore repens ody Nevin drinkingsucsasohtion an aca ersen Percons sittin yonder lod ad Other body Ss: Explar ow cinkingan Sal soltion coud have this et () One the greatest piso ogi dacveres ofthe teat century wae that airman of mined fhcoe and NaCl can promote estore ys Na With the ghuconesoentation nigh enoug inte olution, pense "donee" the ghcone-Na- cotansprtrin neal membranes oficestnalepthelia es promoting Nav uptake in sce poopie Bsplan the corcet bcd this anplation of th eoraporer fer heap srs Te proach has save lions oes 5, Explain why accive ranscort of an ‘on shows saturation kinetics, ‘whereas tarsport of an om throug’ an ion channel does not 6, Whereas elect cal currenes are carted by lec:rons in copper wire, they are car” cc by ions ir aqueous secutions. Explain how an active-transport mechanism can create an electrical current across a membrane. 17. Ce way to produce fres'wate> from seawater is “reverse osmosis," ir which high ~sdrostaie pressures are used to force \water to move against ts dsmotie gracien, from seawater to freshwater, a-ressa membrane. How would yeu ealeulate the minimum hydrostatic pressures recuired? Why might it be preferable to use salty water from a coastal bay diluted with river water rather -han ful-str==gth seawater asthe water souce? 8, Cutline all the >rincipal nsport processes at work inthe three focal exampees shown in Figure 5.1 9. When we discussed the ic mechaniaa of simple diftton we made the f-owing pine Alter th conceirations tf gluon onthe wo side ofa membrane have become egal, glucose meecues contin to ve a random from tt rght dra rom right et the rumbers of glucose molecules going the wo directions ae egeal, however explaining wy te to concentrators stay equalence they have Become equal. Taking achantage othe options -enidedby mule hotopes of erent, how could yu do an expement nan actual hysteal ste, determine whether the pant we have made heres true w The cell merbranes of ramalian re blood cells ar permeable ‘ote. eee ood ellsare dopped in. soto of wes et 'sideniza = osmotie pressure (soared) the cytoplasm o thecelly ltasegh thee s do not owell and urs os gue a8 veren they ae cropped spl nto pure wates they een swell and burst Explain. discuss how yo wo design 2 solution int which eats could be place witht es swelling (Hine Think abeut wheter ute wi stay onthe, ouside the cls ante Inpetion oso presses) {1 Amphibian eggs laid in freshwater exhibit low water permeabilities and thus do not swell and burst osmotically. When {Investigators fist believed they had identified an aquaporin, they manipulated amphibian eggs so the eggs expressed the purported aquaporin protein, When the investigators observed those eggs sivell and burst they knew they had made a ‘monumental discovery: They had found the first aquaporin. Recalling what we have discussed in the text of this chapter regarding red blood cells, explain why tais experiment provided convincing evidence for channiel-mediaced water transport. Go to sites.sinauer.com/animalphys4e for box extensions, quizzes, flashcards, and other resources. REFERENCES AAgre. P2004, Aquaporin water channels (Nobel Lecture). Angow. ‘Chom, 43: 4278-4290. dot: 10.1002/anie. 200460804. A cclghul ‘easy-4o-understond essay on aquaporins, presented by Peter Are ‘on the occasion of his receiving the Nobel Prize fer the escovery of ‘aquaporins, Alberts B.. A. Johnson, J. Lewis, and four adaitional authors. 2014 ‘Molecular Biology of ino Cell, 6th ed. Garland, New York. ‘Bubliz, M., J.P. Morth, and P. Nissen. 2011. P-lype ATPases at lanes. J, Col Si, 124: 2515-2519, Evans, D. H. 201. Freshwater ish gil lon taneport: August Krogh to ‘morpholines and microprobes. Acia Physiol 202: 249-359, Finn, RN. and J. Cerdl, 2015, Evolution and functional alvorsity of ‘aquaporins, Bol, Bull. 229: 6-23. Horold, F. M2001. Cleanings of a chemiosmotlc eye, BioEssays 23: ‘848-856, An intolociually simuloing eseay on the discavery of he Cchemosmoile principle and the navel mplications tsi hes ody. decades later, Kirschner, L.8. 2004. The mechanism of sodium chloride uptake in hhyperregulating aquatic animals. J. Exp. Biol. 207: 1439-1452. Levin, R. 2011, The ancient patterns of workin living systems. In Ri. Levin, S. Laughlin, C. de la Rocha, and A. Blackwell (eds}), Work Meets tite: Exploring the Integrative Study of Work In Living ‘sysloms, pp. 11-38. MIT Press, Cambridge, MA. Focuses on ‘chemiosmass. ‘McWhorter, 7. B.H. Bakken, W. H. Karatoy, and C. Martinez del Rio. 2006. Hummingbirds rely on both paracellular and carrion. mediated intestinal glucose absorption fo fuel high metabolism, Biol. lofi. 2: 131-134, Ponty SF. 1997. The chloride col: Structure and function in the ills, of freshwater fishes. Annu, Rev. Physiol. 89: 325-247, Verkman, A. 8. 2011, Aqueporins ata glance. J. Coll Set. 124: 2107-2112, Voigt, C. C., and J. R. Speakman. 2007. Nectarleeding bats fuel their high metabolism directly with exogenous carbohydrates. Func. Ecol. 21: 913-921. In parallel wiih humming, gore Dots have become nectarlesding specials ‘hat foec white tying. Ths Paper provides on entry point 1 Me large literature on these bats. Weiss, TF. 1996, Cellular Biophysics. MIT Press, Cambridge, MA. Wiison, J. M., . Laurent, B.L. Tufts, and four additional authors "2000. NdCI uptake by the branchial epithelium in freshwater {eleost fish: cn immunological approach to lon-transport protein localization, J Exp. Biol 203: 2279-7296, See.ako Additional References ond Figure and Table Citations,PART II Food, Energy, and TemperaturePART Il Food, Energy, and Temperature CHAPTER 6 m Nutrition, Feeding, and Digestion CHAPTER 7 ™ Energy Metabolism CHAPTER 6 ™ Aerobic and Anaerobic Forms of Metabolism CHAPTER 9 ™ The Energetics of Aerobic Activity CHAPTER 10 @ Thermal Relations CHAPTER 11 ™ Food, Energy, and Temperature AT WORK The Lives of Mammals in Frigid Places Previous page Al crowing animals requite food os © source of matter for constructing their Hisues Trey require food also as a source of energy that enables them to ‘mature into highly erganized, functionally potent organisms despite the sec- tnd law of thermodynamics. Adult mammals donate the essential resources ‘of matior and energy to each new generation,