There are two types of membrane transport proteins—transporters and channels. Both form protein pathways across the lipid bilayer. Whereas transmembrane movement mediated by transporters can be either active or passive, solute flow through channel proteins is always passive. Ion transport across the membrane is influenced by the ion’s concentration gradient and the membrane potential; that is, its electrochemical gradient.

膜转运蛋白有两类——载体蛋白和通道蛋白。二者都在脂双层上形成蛋白质通路。载体蛋白介导的跨膜运动可以是主动的也可以是被动的，而通过通道蛋白的溶质流动则始终是被动的。离子的跨膜转运受其浓度梯度和膜电位共同影响，即受其电化学梯度影响。

All channels and some transporters allow solutes to cross the membrane only passively (“downhill”), a process called passive transport. In the case of transport of a single uncharged molecule, the difference in the concentration on the two sides of the membrane—its concentration gradient—drives passive transport and determines its direction

所有通道蛋白以及部分载体蛋白只允许溶质被动地（「顺坡」）跨膜，这一过程称为被动运输。转运单一不带电分子时，膜两侧的浓度差——即浓度梯度——驱动被动运输并决定其方向。

As explained earlier, because of the action of the Na+-K+ pump, there is little Na+ inside the cell, and other intracellular inorganic cations have to be plentiful enough to balance the charge carried by the cell’s fixed anions—the negatively charged organic molecules that are confined inside the cell. This balancing role is performed largely by K+, which is actively pumped into the cell by the Na+-K+ pump and can also move in or out through the K1 leak channels in the plasma membrane.

如前所述，由于Na⁺-K⁺泵的作用，细胞内Na⁺很少，因此必须有足量的其他胞内无机阳离子来平衡细胞固定阴离子（被限制在细胞内的带负电荷有机分子）所带的电荷。承担这一平衡作用的主要是K⁺：它被Na⁺-K⁺泵主动泵入细胞，也可经质膜上的K⁺渗漏通道进出。

The SR is a specialized type of endoplasmic reticulum that forms a network of tubular sacs in the muscle-cell cytoplasm, and it serves as an intracellular store of Ca2+. When an action potential depolarizes the muscle-cell plasma membrane, Ca2+ is released into the cytosol from the SR through Ca21-release channels, stimulating the muscle to contract

肌质网是一种特化的内质网，在肌细胞胞质中形成管状囊网络，充当细胞内的Ca²⁺储库。当动作电位使肌细胞质膜去极化时，Ca²⁺经Ca²⁺释放通道从肌质网释放到细胞质基质，激发肌肉收缩。

Virtually all eukaryotic cells continually ingest portions of their plasma membrane in the form of small pinocytic (endocytic) vesicles. The rate at which plasma membrane is internalized in this process of pinocytosis varies between cell types, but it is usually surprisingly high. A macrophage, for example, ingests 25% of its own volume of fluid each hour.

几乎所有真核细胞都持续以小胞饮泡（胞吞泡）的形式摄入自身的一部分质膜。不同细胞类型中质膜经胞饮作用被内化的速率不同，但通常高得惊人。例如一个巨噬细胞每小时摄入的液体相当于自身体积的25%。

A particularly well-understood and physiologically important example is the process that mammalian cells use to import cholesterol. Many animal cells take up cholesterol through receptor-mediated endocytosis and, in this way, acquire most of the cholesterol they require to make new membrane. If the uptake is blocked, cholesterol accumulates in the blood and can contribute to the formation in blood vessel (artery) walls of atherosclerotic plaques, deposits of lipid and fibrous tissue that can cause strokes and heart attacks by blocking arterial blood flow.

一个研究得特别透彻、生理上又很重要的例子，是哺乳动物细胞摄取胆固醇的过程。许多动物细胞通过受体介导的胞吞摄取胆固醇，并以此获得合成新膜所需的大部分胆固醇。一旦摄取受阻，胆固醇就在血液中蓄积，可促成血管（动脉）壁上动脉簥样硬化斑块的形成——由脂质和纤维组织构成的沉积物，会阻塞动脉血流而引起中风和心肌梗死。

By generating inorganic ion–concentration differences across the lipid bilayer, cell membranes can store potential energy in the form of electrochemical gradients, which drive various transport processes, convey electrical signals in electrically excitable cells, and (in mitochondria, chloroplasts, and bacteria) are harnessed to make most of the cell’s ATP.

通过在脂双层两侧制造无机离子的浓度差，细胞膜能以电化学梯度的形式储存势能；这些梯度驱动各种转运过程，在可兴奋细胞中传递电信号，并且（在线粒体、叶绿体和细菌中）被用来合成细胞的大部分ATP。

Although water can slowly diffuse across synthetic lipid bilayers, cells use dedicated channel proteins (called water channels, or aquaporins) that greatly increase the permeability of their membranes to water, as we discuss later.

虽然水能缓慢地扩散通过人工脂双层，但细胞使用专门的通道蛋白（称为水通道或水孔蛋白）来大幅提高其膜对水的通透性，这一点后文还会讨论。

Ion channels form aqueous pores across the lipid bilayer and allow inorganic ions of appropriate size and charge to cross the membrane down their electrochemical gradients at rates about 1000 times greater than those achieved by any known transporter. The channels are “gated” and usually open transiently in response to a specific perturbation in the membrane, such as a change in membrane potential (voltage-gated channels), or the binding of a neurotransmitter to the channel (transmitter-gated channels).

离子通道在脂双层上形成含水的孔道，允许大小和电荷合适的无机离子顺各自的电化学梯度跨膜，速率比任何已知载体蛋白高约1000倍。这类通道是「门控」的，通常只在膜受到特定扰动时短暂开放，例如膜电位改变（电压门控通道），或神经递质与通道结合（递质门控通道）。

The second important distinction between ion channels and aqueous pores is that ion channels are not continually open. Instead, they are gated, which allows them to open briefly and then close again. Moreover, with prolonged (chemical or electrical) stimulation, most ion channels go into a closed “desensitized,” or “inactivated,” state, in which they are refractory to further opening until the stimulus has been removed, as we discuss later.

离子通道与普通含水孔道的第二个重要区别是：离子通道并非持续开放，而是门控的，使其能短暂开启后再次关闭。而且在持续的（化学或电）刺激下，大多数离子通道会进入一种关闭的「脱敏」或「失活」状态，在刺激撤除前对进一步开放不再反应。

When an action potential arrives at the presynaptic site, the depolarization of the membrane opens voltage-gated Ca2+ channels that are clustered in the presynaptic membrane. Ca2+ influx triggers the release into the cleft of small signal molecules known as neurotransmitters that are stored in membrane-enclosed synaptic vesicles and released by exocytosis

动作电位到达突触前部位时，膜去极化使聚集在突触前膜的电压门控Ca²⁺通道开放。Ca²⁺内流触发神经递质释放到突触间隙——这些小信号分子储存在有膜包裹的突触小泡内，靠胞吐作用释放。

Unlike the voltage-gated channels responsible for action potentials, transmitter-gated channels are relatively insensitive to the membrane potential and therefore cannot by themselves produce a selfamplifying excitation. Instead, they produce local permeability increases, and hence changes of membrane potential, that are graded according to the amount of neurotransmitter released at the synapse and how long it persists there.

与产生动作电位的电压门控通道不同，递质门控通道对膜电位相对不敏感，因而自身不能产生自我放大的兴奋。它们引起的是局部通透性升高、进而引起膜电位改变，其幅度随突触处释放的神经递质量以及递质滞留时间的长短而分级。

The pores allow specific solutes (such as inorganic ions of appropriate size and charge, and in some cases small molecules, including water, glycerol, and ammonia) to pass through them and thereby cross the membrane. Because no stepwise conformational changes are required once a channel is opened, it is not surprising that transport through channels occurs at a much faster rate than transport mediated by transporters.

这些孔道允许特定溶质通过从而跨膜，包括大小与电荷合适的无机离子，某些情况下还包括水、甘油和氨等小分子。通道一旦开放就不再需要逐步的构象改变，所以通过通道的转运速率远高于载体蛋白介导的转运。

Transporters (sometimes called carriers or permeases) bind the specific solute to be transported and undergo a series of conformational changes that alternately expose solute-binding sites on one side of the membrane and then on the other side to transfer the solute across it. Channels, by contrast, interact much more transiently with the solute to be transported. When opened by conformational changes, channels form continuous pores that extend across the lipid bilayer.

载体蛋白（有时称 carrier 或 permease）结合待转运的特定溶质，并经历一系列构象改变，使溶质结合位点交替暴露于膜的一侧再暴露于另一侧，从而把溶质转运过膜。相比之下，通道蛋白与待转运溶质的相互作用短暂得多；构象改变使其开放时，通道形成贯穿脂双层的连续孔道。

The plasma membrane of all electrically excitable cells—not only neurons, but also muscle, endocrine, and egg cells—contains voltage-gated cation channels, which are responsible for generating the action potentials. An action potential is triggered by a depolarization of the plasma membrane; that is, by a shift in the membrane potential to a less negative value inside.

所有可兴奋细胞的质膜——不只是神经元，还有肌细胞、内分泌细胞和卵细胞——都含有电压门控阳离子通道，动作电位由它们产生。动作电位由质膜去极化触发，即膜电位向膜内负值减小的方向移动。

Each domain also contains a voltage sensor that is characterized by an unusual transmembrane helix, S4, that contains many positively charged amino acids. When the membrane is polarized, these charges are exposed on the negatively charged cytosolic side of the membrane. Because of the charge compensation, this conformation is thermodynamically stabilized in a polarized membrane. As the membrane becomes depolarized, the S4 helices experience the electrostatic force that now stabilizes an alternative conformation in which the helices have twisted and expose the charges to the opposite, extracellular side of the membrane.

每个结构域还含有一个电压感受器，其特征是一条不寻常的跨膜螺旋S4，内含许多带正电荷的氨基酸。膜处于极化状态时，这些电荷暴露在膜的带负电荷的胞质侧；由于电荷补偿，该构象在极化膜中被热力学稳定。当膜去极化时，S4螺旋受到静电力作用，此时被稳定的是另一种构象——螺旋发生扭转，把电荷暴露到膜的另一侧即胞外侧。

In addition to the direct diffusion of water across the lipid bilayer, some prokaryotic and eukaryotic cells have water channels, or aquaporins, embedded in their plasma membranes to allow water to move more rapidly. Aquaporins are particularly abundant in animal cells that must transport water at high rates, such as the epithelial cells of the kidney or exocrine cells that must transport or secrete large volumes of fluids

除水分子直接经脂双层扩散外，一些原核细胞和真核细胞的质膜上还嵌有水通道（水孔蛋白），使水的移动更快。水孔蛋白在必须高速转运水的动物细胞中特别丰富，例如肾的上皮细胞，以及必须转运或分泌大量液体的外分泌细胞。

The pore is too narrow for any hydrated ion to enter, and the energy cost of dehydrating an ion would be enormous because the hydrophobic wall of the pore cannot interact with a dehydrated ion to compensate for the loss of water. This design readily explains why the aquaporins cannot conduct K+, Na+, Ca2+, or Cl– ions.

孔道太窄，任何水合离子都进不去；而使离子脱水的能量代价极大，因为孔道的疏水壁无法与脱水离子相互作用来补偿失水的损失。这一设计很容易解释水孔蛋白为何不能通过K⁺、Na⁺、Ca²⁺或Cl⁻。

The last type of transport ATPase that we discuss here is the family of ABC transporters, so named because each member contains two highly conserved ATPase domains, or ATP-binding “cassettes,” on the cytosolic side of the membrane. ATP binding brings together the two ATPase domains, and ATP hydrolysis leads to their dissociation

本节讨论的最后一类转运ATP酶是ABC转运蛋白家族，得名于每个成员在膜的胞质侧都含有两个高度保守的ATP酶结构域，即ATP结合「盒」。ATP结合使这两个ATP酶结构域靠拢，ATP水解则使它们解离。

Although each transporter is thought to be specific for a particular molecule or class of molecules, the variety of substrates transported by this superfamily is great and includes inorganic ions, amino acids, monosaccharides and polysaccharides, peptides, lipids, drugs, and, in some cases, even proteins that can be larger than the transporter itself. The first eukaryotic ABC transporters identified were discovered because they pump hydrophobic drugs out of the cytosol. One of these transporters is the multidrug resistance (MDR) protein, also called P-glycoprotein.

虽然每种转运蛋白被认为只对某一特定分子或某类分子有特异性，但这个超家族转运的底物种类极多，包括无机离子、氨基酸、单糖和多糖、肽、脂质、药物，某些情况下甚至包括比转运蛋白本身还大的蛋白质。最早被鉴定出来的真核ABC转运蛋白，是因为能把疏水性药物泵出细胞质基质而被发现的；其中之一就是多药抗性（MDR）蛋白，又称P-糖蛋白。

In addition to passive transport, cells need to be able to actively pump certain solutes across the membrane “uphill,” against their electrochemical gradients. Such active transport is mediated by transporters whose pumping activity is directional because it is tightly coupled to a source of metabolic energy, such as an ion gradient or ATP hydrolysis, as discussed later. Transmembrane movement of small molecules mediated by transporters can be either active or passive, whereas that mediated by channels is always passive

除被动运输外，细胞还须能把某些溶质逆电化学梯度「上坡」主动泵过膜。这种主动运输由载体蛋白介导，其泵送具有方向性，因为它与代谢能量来源紧密偶联，如离子梯度或ATP水解。载体蛋白介导的小分子跨膜运动可以是主动的也可以是被动的，而通道蛋白介导的则始终是被动的。

ATP-driven pumps are often called transport ATPases because they hydrolyze ATP to ADP and phosphate and use the energy released to pump ions or other solutes across a membrane. There are three principal classes of ATP-driven pumps

ATP驱动泵常被称为转运ATP酶，因为它们把ATP水解为ADP和磷酸，并利用释放的能量把离子或其他溶质泵过膜。ATP驱动泵主要有三类。

Enzymatic studies and analyses of the three-dimensional structures of transport intermediates of the SR Ca2+ pump and related pumps have revealed the molecular mechanism of P-type transport ATPases in great detail. They all have similar structures, containing 10 transmembrane α helices connected to three cytosolic domains

对肌质网Ca²⁺泵及相关泵的转运中间体所做的酶学研究和三维结构分析，已十分详尽地揭示了P型转运ATP酶的分子机制。它们的结构都相似，含10个跨膜α螺旋，连接3个胞质侧结构域。

Ca2+ binding triggers a series of conformational changes that close the passageway to the cytosol and activate a phosphotransfer reaction in which the terminal phosphate of the ATP is transferred to an aspartate that is conserved among all P-type ATPases. The ADP then dissociates and is replaced with a fresh ATP, causing another conformational change that opens a passageway to the SR lumen through which the two Ca2+ ions exit.

Ca²⁺结合触发一系列构象改变，关闭通向细胞质基质的通路，并激活一次磷酸基转移反应——ATP的末端磷酸被转移到一个在所有P型ATP酶中都保守的天冬氨酸残基上。随后ADP解离，由新的ATP取代，引起另一次构象改变，打开通向肌质网腔的通路，2个Ca²⁺由此排出。

The nonselective constitutive secretory pathway transports most other proteins directly to the cell surface. Because entry into this pathway does not require a particular signal, it is also called the default pathway. Thus, in an unpolarized cell such as a white blood cell or a fibroblast, it seems that any protein in the lumen of the Golgi apparatus is automatically carried by the constitutive pathway to the cell surface unless it is specifically returned to the ER, retained as a resident protein in the Golgi apparatus itself, or selected for the pathways that lead to regulated secretion or to endosomes.

非选择性的组成型分泌途径把其余大多数蛋白质直接送到细胞表面。由于进入该途径不需要特定信号，它又称为默认途径。因此，在白细胞、成纤维细胞这类非极性细胞中，高尔基体腔内的任何蛋白质似乎都会被组成型途径自动带到细胞表面，除非它被专门送回内质网、作为驻留蛋白留在高尔基体内，或被选入通向调节型分泌或内体的途径。

When a secretory vesicle fuses with the plasma membrane, its contents are discharged from the cell by exocytosis and its membrane becomes part of the plasma membrane. Although this should increase the surface area of the plasma membrane, it does so only transiently, because an equivalent amount of membrane is removed from the surface by endocytosis almost as fast as it is added by exocytosis, a process reminiscent of the endocytic–exocytic cycle discussed later.

分泌泡与质膜融合时，其内含物经胞吐作用排出细胞，其膜则成为质膜的一部分。虽然这本应增加质膜表面积，但这种增加只是暂时的，因为胞吞作用几乎以同样快的速度从表面移走等量的膜，这一过程令人想到后文讨论的胞吞-胞吐循环。

The Ca2+ pump, which accounts for about 90% of the membrane protein of the SR, moves Ca2+ from the cytosol back into the SR. The endoplasmic reticulum of non-muscle cells also stores Ca2+ using a closely homologous Ca2+ pump and Ca2+-release channels.

Ca²⁺泵约占肌质网膜蛋白的90%，它把Ca²⁺从细胞质基质送回肌质网。非肌细胞的内质网也用一种高度同源的Ca²⁺泵和Ca²⁺释放通道储存Ca²⁺。

Phagocytosis is a special form of endocytosis in which a cell uses large endocytic vesicles called phagosomes to ingest large particles such as microorganisms and dead cells. Phagocytosis is distinct, both in purpose and mechanism, from macropinocytosis, which we discussed earlier. In protozoa, phagocytosis is a form of feeding: large particles taken up into phagosomes end up in lysosomes, and the products of the subsequent digestive processes pass into the cytosol to be used as food.

吞噬作用是胞吞作用的一种特殊形式，细胞用称为吞噬体的大型胞吞泡摄入微生物、死细胞等大颗粒。吞噬作用在目的和机制上都不同于前面讨论过的大型胞饮作用。在原生动物中，吞噬作用是一种取食方式：进入吞噬体的大颗粒最终到达溶酶体，随后消化产生的产物进入细胞质基质作为食物利用。

Phagocytosis is a cargo-triggered process. That is, it requires the activation of cell-surface receptors that transmit signals to the cell interior. Thus, to be phagocytosed, particles must first bind to the surface of the phagocyte (although not all particles that bind are ingested). Phagocytes have a variety of cell-surface receptors that are functionally linked to the phagocytic machinery of the cell.

吞噬作用是由货物触发的过程，也就是说，它需要细胞表面受体被激活并把信号传向细胞内部。因此，颗粒要被吞噬，必先结合到吞噬细胞表面（不过并非所有结合上去的颗粒都会被摄入）。吞噬细胞具有多种细胞表面受体，它们在功能上与细胞的吞噬机器相连。

Two important properties distinguish ion channels from aqueous pores. First, they show ion selectivity, permitting some inorganic ions to pass, but not others. This suggests that their pores must be narrow enough in places to force permeating ions into intimate contact with the walls of the channel so that only ions of appropriate size and charge can pass.

有两个重要性质把离子通道与普通含水孔道区分开。第一，它们表现出离子选择性，只让某些无机离子通过而不让另一些通过。这说明其孔道必有足够狭窄之处，迫使通过的离子与通道壁紧密接触，因而只有大小和电荷合适的离子才能通过。

Eukaryotic cells maintain very low concentrations of free Ca2+ in their cytosol (∼10–7 M) in the face of a very much higher extracellular Ca2+ concentration (∼10–3 M). Therefore, even a small influx of Ca2+ significantly increases the concentration of free Ca2+ in the cytosol, and the flow of Ca2+ down its steep concentration gradient in response to extracellular signals is one means of transmitting these signals rapidly across the plasma membrane

真核细胞把细胞质基质中的游离Ca²⁺维持在很低浓度（约10⁻⁷ M），而胞外Ca²⁺浓度要高得多（约10⁻³ M）。因此，哪怕少量Ca²⁺内流也会显著提高胞质游离Ca²⁺浓度；Ca²⁺响应胞外信号顺其陡峭的浓度梯度流动，正是把信号迅速传过质膜的一种方式。

Whereas transport vesicles containing materials for constitutive release fuse with the plasma membrane once they arrive there, secretory vesicles in the regulated pathway wait at the membrane until the cell receives a signal for the vesicles to secrete their cargo. The signal can be an electrical nerve impulse (an action potential) or an extracellular signal molecule, such as a hormone. In either case, it leads to a transient increase in the concentration of free Ca2+ in the cytosol, which is the trigger for secretory vesicle fusion.

载有组成型释放物质的转运膜泡一到达质膜就与之融合；而调节型途径的分泌泡则停在膜下等待，直到细胞收到让其分泌内含物的信号。该信号可以是电性的神经冲动（动作电位），也可以是激素等胞外信号分子。两种情况下，信号都会使细胞质基质中游离Ca²⁺浓度短暂升高，这正是分泌泡融合的触发因素。

Others function as coupled transporters, in which the transfer of one solute strictly depends on the transport of a second. Coupled transport involves either the intimately coupled transfer of a second solute in the same direction, performed by symporters (also called co-transporters), or the transfer of a second solute in the opposite direction, performed by antiporters (also called exchangers)

另一些载体蛋白作为偶联转运蛋白工作，其中一种溶质的转移严格依赖于第二种溶质的转运。偶联转运要么由同向转运蛋白（协同转运蛋白）把第二种溶质紧密偶联地朝同一方向转移，要么由反向转运蛋白（交换体）把第二种溶质朝相反方向转移。

In bacteria, yeasts, and plants, as well as in many membrane-enclosed organelles of animal cells, most ion-driven active transport systems depend on H+ rather than Na+ gradients, reflecting the predominance of H+ pumps in these membranes. An electrochemical H+ gradient across the bacterial plasma membrane, for example, drives the inward active transport of many sugars and amino acids.

在细菌、酵母和植物中，以及在动物细胞的许多被膜细胞器上，大多数由离子驱动的主动运输系统依赖H⁺梯度而非Na⁺梯度，这反映了这些膜上以H⁺泵为主。例如细菌质膜两侧的H⁺电化学梯度，就驱动着许多糖和氨基酸向内的主动运输。

Such ion-driven coupled transporters are said to mediate secondary active transport. The Na+ that enters the cell during coupled transport is subsequently pumped out by an ATP-driven Na+-K+ pump in the plasma membrane (as we discuss later), which, by exchanging K+ for Na+, maintains the Na+ gradient, indirectly driving the coupled transport. Such ATP-driven pumps are therefore said to mediate primary active transport because in these the free energy of ATP hydrolysis is used to directly drive the transport of a solute against its electrochemical gradient.

这类由离子驱动的偶联转运蛋白被称为介导次级主动运输。偶联转运过程中进入细胞的Na⁺，随后被质膜上由ATP驱动的Na⁺-K⁺泵泵出；该泵以K⁺交换Na⁺，维持Na⁺梯度，从而间接驱动偶联转运。因此这类ATP驱动泵被称为介导初级主动运输，因为其中ATP水解的自由能被直接用来驱动溶质逆电化学梯度的转运。

An Na1-K1 pump, or Na1-K1 ATPase, found in the plasma membrane of virtually all animal cells, maintains these concentration differences. Like the Ca2+ pump, the Na+-K+ pump belongs to the family of P-type ATPases and operates as an ATP-driven antiporter, actively pumping Na+ out of the cell against its steep electrochemical gradient and pumping K+ in

几乎所有动物细胞质膜上都有的Na⁺-K⁺泵（Na⁺-K⁺ATP酶）维持着这些浓度差。与Ca²⁺泵一样，Na⁺-K⁺泵属于P型ATP酶家族，作为ATP驱动的反向转运蛋白工作，主动把Na⁺逆其陡峭的电化学梯度泵出细胞，同时把K⁺泵入。

Because ligands are selectively captured by receptors, receptor-mediated endocytosis provides a selective concentrating mechanism that increases the efficiency of internalization of particular ligands more than a hundredfold. In this way, even minor components of the extracellular fluid can be efficiently taken up in large amounts.

由于配体被受体选择性捕获，受体介导的胞吞提供了一种选择性浓缩机制，使特定配体的内化效率提高100倍以上。这样，即使是胞外液中含量很少的成分也能被大量高效地摄取。

AP2 then recruits clathrin to initiate endocytosis. Because coated pits constantly pinch off to form coated vesicles, any LDL particles bound to LDL receptors in the coated pits are rapidly internalized in coated vesicles. After shedding their clathrin coats, the vesicles deliver their contents to early endosomes. Once the LDL and LDL receptors encounter the low pH in early endosomes, LDL is released from its receptor and is delivered via late endosomes to lysosomes. There, the cholesterol esters in the LDL particles are hydrolyzed to free cholesterol, which is now available to the cell for new membrane synthesis

随后AP2招募网格蛋白，启动胞吞。由于有被小窝不断缢缩形成有被小泡，凡是结合在有被小窝内LDL受体上的LDL颗粒都被迅速内化进有被小泡。小泡脱去网格蛋白外被后，把内容物送入早期内体。LDL和LDL受体一旦遇到早期内体中的低pH，LDL即从受体上释放，经晚期内体送到溶酶体。在溶酶体中，LDL颗粒里的胆固醇酯被水解为游离胆固醇，供细胞合成新膜使用。

In some cases, the receptor is lacking altogether. In others, the receptors are defective—in either the extracellular binding site for LDL or the intracellular binding site for the AP2 adaptor protein in clathrin-coated pits. In the latter case, normal numbers of LDL receptors are present, but they fail to become localized in clathrin-coated pits. Although LDL binds to the surface of these mutant cells, it is not internalized, directly demonstrating the importance of clathrin-coated pits for the receptor-mediated endocytosis of cholesterol.

有些病例中受体完全缺失；另一些病例中受体有缺陷——或是LDL的胞外结合位点异常，或是网格蛋白有被小窝内衔接蛋白AP2的胞内结合位点异常。后一种情况下LDL受体数量正常，却无法定位到网格蛋白有被小窝中。这类突变细胞表面虽能结合LDL，却不能把它内化，这直接证明了网格蛋白有被小窝对胆固醇受体介导胞吞的重要性。

Early endosomes are the main sorting stations in the endocytic pathway, just as the cis and trans Golgi networks serve this function in the secretory pathway. In the mildly acidic environment of the early endosome, many internalized receptor proteins change their conformation and release their ligand, as already discussed for the M6P receptors.

早期内体是胞吞途径中主要的分选站，正如高尔基体顺面网状结构和反面网状结构在分泌途径中所起的作用。在早期内体的弱酸性环境中，许多被内化的受体蛋白改变构象并释放其配体，这一点在讨论M6P受体时已经提过。

The major protein component of clathrin-coated vesicles is clathrin, which forms the outer layer of the coat. Clathrin is composed of a large subunit (the heavy chain) and a small subunit (the light chain). Three heavy chains and three light chains assemble into a three-legged structure called a triskelion

网格蛋白有被小泡的主要蛋白成分是网格蛋白，它构成外被的外层。网格蛋白由一个大亚基（重链）和一个小亚基（轻链）组成。3条重链和3条轻链装配成一个三脚结构，称为三脚蛋白复合体。

Because the Na+-K+ pump drives three positively charged ions out of the cell for every two it pumps in, it is electrogenic: it drives a net electric current across the membrane, tending to create an electrical potential, with the cell’s inside being negative relative to the outside. This electrogenic effect of the pump, however, seldom directly contributes more than 10% to the membrane potential. The remaining 90%, as we discuss later, depends only indirectly on the Na+-K+ pump.

Na⁺-K⁺泵每泵入2个正离子就泵出3个，因此是生电性的：它驱动净电流跨膜，倾向于产生一个膜内相对膜外为负的电位。不过泵的这种生电效应对膜电位的直接贡献很少超过10%，其余90%只是间接依赖Na⁺-K⁺泵。

Some transporters move a single solute “downhill,” whereas others can act as pumps to move a solute “uphill” against its electrochemical gradient, by using energy provided by ATP hydrolysis, by a downhill flow of another solute (such as Na1 or H1), or by light to drive the requisite series of conformational changes in an orderly manner. Transporters belong to a small number of protein families. Each family evolved from a common ancestral protein, and its members all operate by a similar mechanism. The family of P-type transport ATPases, which includes Ca21 and Na1-K1 pumps, is an important example; each of these ATPases sequentially phosphorylates and dephosphorylates itself during the pumping cycle.

有些载体蛋白只把单一溶质「顺坡」运输，另一些则可作为泵把溶质「逆坡」逆其电化学梯度转运，能量来自ATP水解、另一种溶质（如Na⁺或H⁺）的顺梯度流动，或来自光，用以有序地驱动所需的一系列构象改变。载体蛋白只归属于少数几个蛋白质家族。每个家族都由一个共同的祖先蛋白演化而来，成员的工作机制都相似。P型转运ATP酶家族即是一个重要例子，它包括Ca²⁺泵和Na⁺-K⁺泵，这些ATP酶在泵送循环中依次使自身磷酸化和去磷酸化。

When a cell needs cholesterol for membrane synthesis, it makes transmembrane receptor proteins for LDL at the ER and transports them to the plasma membrane. Once in the plasma membrane, the LDL receptor diffuses until an endocytosis signal in its cytoplasmic tail binds the adaptor protein AP2 after AP2’s conformation has been locally unlocked by binding to PI(4,5)P2 on the plasma membrane.

细胞需要胆固醇合成膜时，就在内质网上合成LDL的跨膜受体蛋白，并把它们运到质膜。到达质膜后，LDL受体在膜上扩散，直到其胞质尾部的胞吞信号与衔接蛋白AP2结合——此前AP2须先结合质膜上的PI(4,5)P₂，构象被局部解锁。

Aquaporins contain two strategically placed asparagines, which bind to the oxygen atom of the central water molecule in the line of water molecules traversing the pore, imposing a bipolarity on the entire single-file column of water molecules

水孔蛋白含有两个位置关键的天冬酰胺残基，它们结合穿过孔道的那列水分子中中央那个水分子的氧原子，使整列单行排列的水分子呈现两极性。

Aquaporins must solve a problem that is opposite to that facing ion channels. To avoid disrupting ion gradients across membranes, they have to allow the rapid passage of water molecules while completely blocking the passage of ions. The three-dimensional structure of an aquaporin reveals how it achieves this remarkable selectivity.

水孔蛋白必须解决一个与离子通道相反的问题：为避免破坏膜两侧的离子梯度，它们必须让水分子快速通过，同时完全阻断离子通过。水孔蛋白的三维结构揭示了它如何实现这种非凡的选择性。

Na+-linked symporters located in the apical (absorptive) domain of the plasma membrane actively transport nutrients into the cell, building up substantial concentration gradients for these solutes across the plasma membrane. Uniporters in the basal and lateral (basolateral) domain allow the nutrients to leave the cell passively down these concentration gradients to enter the bloodstream for use in the rest of the body.

位于质膜顶端（吸收）域的Na⁺偶联同向转运蛋白把营养物主动转运进细胞，在质膜两侧为这些溶质建立起相当大的浓度梯度。基底侧（基底面与侧面）域的单向转运蛋白则让营养物顺这些浓度梯度被动离开细胞，进入血流供全身使用。

Cells also contain a high concentration of solutes, including numerous negatively charged organic molecules that are confined inside the cell (the so-called fixed anions) and their accompanying cations that are required for charge balance. This creates an osmotic gradient, which mostly is balanced by an opposite osmotic gradient due to a high concentration of inorganic ions—chiefly Na+ and Cl–—in the extracellular fluid. The small remaining osmotic force tends to “pull” water into the cell, causing it to swell until the forces are balanced.

细胞内还含有高浓度溶质，包括大量被限制在细胞内的带负电荷有机分子（所谓固定阴离子）以及为平衡电荷而伴随的阳离子。这造成一个渗透梯度，它大体被胞外液中高浓度无机离子（主要是Na⁺和Cl⁻）产生的相反渗透梯度所抵消。剩下的微小渗透力倾向于把水「拉」进细胞，使细胞膨胀，直到各力平衡。

In general, the smaller the molecule and the more hydrophobic, or nonpolar, it is, the more easily it will diffuse across a lipid bilayer. Small nonpolar molecules, such as O2 and CO2, readily dissolve in lipid bilayers and therefore diffuse rapidly across them. Small uncharged polar molecules, such as water or urea, also diffuse across a bilayer, albeit much more slowly

一般来说，分子越小、疏水性（非极性）越强，就越容易扩散通过脂双层。O₂和CO₂这类小的非极性分子易溶于脂双层，因而扩散得很快。水或尿素这类小的不带电极性分子也能扩散通过脂双层，只是慢得多。