3 Биологические мембраны. Обмен веществом (1160072), страница 14
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The 12 transmembrane segments of the permease form a hydrophilicpath through the hydrophobic center of the membrane.energy state comparable to the transition state in an enzyme-catalyzedchemical reaction. In both cases, an activation barrier must be overcome to reach the intermediate stage (Fig.
10-17; compare with Fig.8-4). The energy of activation for translocation of a polar solute acrossthe bilayer is so large that pure lipid bilayers are virtually impermeable to polar and charged species over the periods of time important tocells.Water itself is an exception to this generalization. Although polar,it diffuses rapidly across biological membranes by mechanisms notfully understood. When the solute concentrations on two sides of amembrane are very different, there is a concentration gradient of solvent (water) molecules, and this osmotic imbalance results in thetransmembrane flux of water until the osmotic strength equalizes onboth sides of the membrane. A few biologically important gases alsocross membranes by simple diffusion: molecular oxygen (O2), nitrogen(N2), and methane (CH4), all of which are relatively nonpolar.Transmembrane passage of polar compounds and ions is made possible by membrane proteins that lower the activation energy for transport by providing an alternative path for specific solutes through thelipid bilayer.
Proteins that bring about this facilitated diffusion orpassive transport are not enzymes in the usual sense; their "substrates" are moved from one compartment to another, but are notchemically altered. Membrane proteins that speed the movement of asolute across a membrane by facilitating diffusion are called transporters or permeases.The kind of detailed structural information obtained for many soluble enzymes by x-ray crystallography is not yet available for mostmembrane transporters; as a group, these proteins are both difficult topurify and difficult to crystallize.
However, from studies of the specificity and kinetics of transporters it is clear that their action is closelyanalogous to that of enzymes. Like enzymes, transporters bind theirsubstrates through many weak, noncovalent interactions and with stereochemical specificity. The negative free-energy change that occurswith these weak interactions, AGbinding, counterbalances the positivefree-energy change that accompanies loss of the water of hydrationfrom the substrate, AGdehydration, thereby lowering the activation energy, AG*, for transmembrane passage (Fig. 10-17). Transporter proteins span the lipid bilayer at least once, and usually several times,forming a transmembrane channel lined with hydrophilic amino acidside chains. The channel provides an alternative path for its specificsubstrate to move across the lipid bilayer, without having to dissolve init, further lowering AG" for transmembrane diffusion.
The result is anincrease of orders of magnitude in the rate of transmembrane passageof the substrate.The Glucose Permease of ErythrocytesMediates Passive TransportEnergy-yielding metabolism in the erythrocyte depends on a constantsupply of glucose from the blood plasma, where its concentration ismaintained at about 5 mM. Glucose enters the erythrocyte by facilitated diffusion via a specific glucose permease (Fig.
10-18). This integral membrane protein (Mr 45,000) has 12 hydrophobic segments, andprobably spans the membrane 12 times. It allows glucose entry into thecell at a rate about 50,000 times greater than its unaided diffusionthrough a lipid bilayer. Because glucose transport into erythrocytes isa typical example of passive transport, we will look at it in some detail.Extracellular glucoseconcentration, [S]out (HIM)The process of glucose transport can be described by analogy withan enzymatic catalysis in which the "substrate" is glucose outside thecell (Sout)> the "product" is glucose inside (Sin), and the "enzyme" is thetransporter, T.
When the rate of glucose uptake is measured as a function of external glucose concentration (Fig. 10-19), the resulting plot ishyperbolic; at high external glucose concentrations the rate of uptakeapproaches Vmax. Formally, such a transport process can be describedby the equationsFigure 10-19 The initial rate of glucose entry intoan erythrocyte depends upon the initial concentration of glucose on the outside, [S]out. The kinetics offacilitated diffusion are analogous to the kinetics ofan enzyme-catalyzed reaction. Compare these plotswith Fig.
8-11, and Fig. 1 in Box 8-1. Note that Ktis analogous to Km, the Michaelis-Menten constant.in which kh k-i, etc., are the forward and reverse rate constants foreach step. The first step is the binding of glucose to a stereospecific siteon the transporter protein on the exterior surface of the membrane;step 2 is the transmembrane passage of the substrate; and step 3 is therelease of the substrate (product), now on the inner surface of themembrane, from the transporter into the cytoplasm.The rate equations for this process can be derived exactly as forenzyme-catalyzed reactions (Chapter 8), yielding an expression analogous to the Michaelis-Menten equation:Kt + [S] o u tin which Vo is the initial velocity of accumulation of glucose inside thecell when its concentration in the surrounding medium is [S] out , and Kt(^transport) is a constant, analogous to the Michaelis-Menten constant,a combination of rate constants characteristic of each transport system.
This equation describes the initial velocity—the rate observedwhen [S]in = 0.Because no chemical bonds are made or broken in the conversion ofSout into Sin, neither "substrate" nor "product" is intrinsically morestable, and the process of entry is therefore fully reversible. As [S]inapproaches [S]out, the rates of entry and exit become equal.
Such asystem is therefore incapable of accumulating the substrate (glucose)within cells at concentrations above that in the surrounding medium;it simply achieves equilibration of glucose on the two sides of the membrane at a much higher rate than would occur in the absence of aspecific transporter. The glucose transporter is specific for D-glucose,for which the measured Kt is 1.5 mM. For the close analogs D-mannoseand D-galactose, which differ only in the position of one hydroxyl group,the values of Kt are 20 and 30 mM, respectively, and for L-glucose, Ktexceeds 3,000 HIM! (Recall that a high Kt generally reflects a low affinity of transporter for substrate.) The glucose transporter of the erythrocyte therefore shows the three hallmarks of passive transport: highrates of diffusion down a concentration gradient, saturability, andspecificity.285286Part II Structure and CatalysisCarbon dioxide producedby catabolism enterserythrocyteCOChloride-bicarbonate vexchange proteinAt respiring tissuesBicarbonatedissolves inblood plasmaHCO3 Cl~Figure 10-20 The chloride-bicarbonate exchangerof the erythrocyte membrane allows the entry andexit of HCO3 without changes in the transmembrane electrical potential.
The role of this shuttlesystem is to increase the CO2-carrying capacity ofthe blood.carbonic anhydraseCO2 + H2O> HCO3 + H +ClChloride and Bicarbonate Are Cotransportedacross the Erythrocyte Membraneco 2Carbon dioxide leaveserythrocyte and isexhaledHCO3crBicarbonate enterserythrocyte fromblood plasmaUniportCotransportFigure 10-21 The three general classes of transport systems differ in the number of solutes (substrates) transported and the direction in whicheach is transported. Examples of all three types oftransporters are discussed in the text.
Note thatthis classification tells us nothing about whetherthese are energy-requiring (active transport) or energy-independent (passive transport) processes.The erythrocyte contains another facilitated diffusion system, an anionexchanger, which is essential in CO2 transport from tissues such asmuscle and liver to the lungs. Waste CO2 released from respiring tissues into the blood plasma enters the erythrocyte, where it is convertedinto bicarbonate (HCO3) by the enzyme carbonic anhydrase (Fig. 1020).
The HCO3 reenters the blood plasma for transport to the lungs.Because HCO3 is much more soluble in blood plasma than is CO2, thisroundabout route increases the blood's capacity to carry carbon dioxidefrom the tissues to the lungs. In the lungs, HCO3 reenters the erythrocyte and is converted to CO2, which is eventually exhaled. For thisshuttle to be effective, very rapid movement of HCO3 across the erythrocyte membrane is required.The chloride-bicarbonate exchanger, also called the anionexchange protein, or (for historical reasons) band 3, increases thepermeability of the erythrocyte membrane to HCO3 by a factor of morethan a million. Like the glucose transporter, it is an integral membrane protein that probably spans the membrane 12 times.
Unlike theglucose transporter, this protein mediates a bidirectional exchange; foreach HCO3 ion that moves in one direction, one Cl~ ion must move inthe opposite direction (Fig. 10-20). The result of this paired movementof two monovalent anions is no net change in the charge or electricalpotential across the erythrocyte membrane; the process is not electrogenie.
The coupling of Cl" and HCO3 movement is obligatory; in theabsence of chloride, bicarbonate transport stops. In this respect, theanion exchanger resembles many other systems that simultaneouslycarry two solutes across a membrane, all of which are called cotransport systems. When, as in this case, the two substrates move in opposite directions, the process is antiport. In symport, two substratesare moved simultaneously in the same direction (Fig. 10-21). Transporters that carry only one substrate, such as the glucose permease,are sometimes called uniport systems.Active Transport Results in Solute Movementagainst a Concentration GradientIn passive transport, the transported species always moves down itsconcentration gradient, and no net accumulation occurs.
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