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1 Cell and Membrane Physiology

C. Carriers Larger solutes, such as sugars and amino acids, are typically as- sisted across the membrane by carriers. Carriers can be considered enzymes that catalyze movement rather than a biochemical reaction. Translocation involves a binding step, which slows transport rate con- siderably compared with pores and channels (see Table 1.2). There are three principal carrier modes: facilitated diffusion , primary active transport , and secondary active transport . 1. Transport kinetics: Carriers, like enzymes, show substrate specificity, saturation kinetics (Michaelis-Menten kinetics), and susceptibility to competition. A general scheme for carrier-medi- ated transport envisions a solute-binding step, a change in car- rier conformation that reveals a conduit through which the solute may pass, and then release on the opposite side of the mem- brane (Figure 1.13). When solute concentrations are low, carrier- mediated transport is more efficient than simple diffusion, but a finite number of solute binding sites means that a carrier can satu- rate when substrate concentrations are high (Figure 1.14). The transport rate at which saturation occurs is known as the trans- port maximum ( T m ) and is the functional equivalent of V max that defines maximal reaction velocity catalyzed by an enzyme. 1 2. Facilitated diffusion: The simplest carriers use electrochemi- cal gradients as a motive force (facilitated diffusion) as shown in Figure 1.15A.They simply provide a selective pathway by which or- ganic solutes, such as glucose, organic acids, and urea, can move across the membrane down their electrochemical gradients. The binding step ensures selectivity of passage. Common examples of such carriers includes the GLUT family of glucose transporters and the renal tubule urea transporter (see 27·V·D). The GLUT1 trans- porter is ubiquitous and provides a principal pathway by which all cells take up glucose. GLUT4 is an insulin-regulated glucose trans- porter expressed primarily in adipose tissue and muscle. 3. Primary active transport: Moving a solute uphill against its electrochemical gradient requires energy. Primary active trans- porters are ATPases that move or “pump” solutes across mem- branes by hydrolyzing adenosine triphosphate (ATP) as shown in Figure 1.15B. There are three main types of pump, all related P-type ATPase family members: a Na -K ATPase , a group of Ca 2 ATPases , and a H -K ATPase . a. Na -K ATPase : The Na -K ATPase ( Na -K exchanger or Na -K pump ) is common to all cells and uses the energy of a single ATP molecule to transport three Na out of the cell, while simultaneously bringing two K back from the ECF. Movement of both ions occurs uphill against their respective electrochemical gradients. The physiologic importance of the Na -K ATPase cannot be overstated. The Na and K gradi- ents it establishes permit electrical signaling in neurons and

1

A solute binds to a site within the carrier protein on one side of the membrane.

Carrier

Binding site

Conformational change reveals a hydrophilic path to the opposite side of the membrane.

2

Intracellular fluid

Solute is released. Carriers work in the reverse direction also.

3

Figure 1.13 Model for transport by a carrier protein.

Transport maximum (T m )

Carrier- mediated transport

Transport rate

Simple diffusion

Concentration

1 For further discussion of enzymatic maximal velocity, see LIR Biochemistry, 5e, p. 56.

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Figure 1.14 Carrier saturation kinetics.

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