BIOCHEMISTRY - L. Stryer - 1984

VOLUME 3

PART V. MOLECULAR PHYSIOLOGY

CHAPTER 36. MEMBRANE TRANSPORT

Summary

The Transport of Molecules and ions across Introduction/36.html">Biological Membranes is mediated by transmembrane-oriented Proteins that form channels. Transport is passive if ∆G for the transported species is negative; in the case of Active Transport, ∆G is positive. Changes in Free energy depend on the concentration ratio of the transported species across the membrane and on the Membrane Potential, if the membrane is charged. Active transport requires an input of free energy. The most widespread transport system in animal Cells is the (Na⁺ + K⁺)-pump, which extrudes three Na⁺ ions and pumps in two K⁺ ions at the expense of the Hydrolysis of a single ATP molecule. In the presence of Na⁺, ATP phosphorylates an aspartate side chain in the α-subunit of this enzymatic complex, which has an α₂β₂ subunit composition. The resulting phosphorylated intermediate is hydrolyzed in the presence of K⁺. This final reaction is inhibited by cardiotonic Steroids (such as digitalis), which are highly specific Inhibitors of the (Na⁺ + K⁺)-pump. The translocation of Na⁺ and K⁺ ions is driven by a cycle of conformational changes governed by phosphorylation and dephosphorylation. The transport of Calcium Ions, which play a crucial role in the Regulation of Muscle contraction, is carried out by a different ATPase system localized in the sarcoplasmic reticulum membrane. However, in this case as well, the transport process is coupled to the phosphorylation of an aspartate residue. Both transport systems—for both Ca²⁺ and (Na⁺ + K⁺)—have been successfully reconstituted from purified ATPases and Phospholipids.

For A number of transport systems, the immediate source of energy is an ion concentration gradient rather than ATP hydrolysis. For instance, The active transport of glucose and Amino Acids in various animal cells is coupled to the simultaneous influx of Na⁺; this process is termed cotransport. The simultaneous influx of Na⁺ and glucose is driven by a specific symport. The (Na⁺ + K⁺)-pump establishes the Na⁺ concentration gradient required for the coupled influx of Na⁺ and glucose. In Bacteria, the immediate energy source for symports and antiports is typically a H⁺ concentration gradient rather than a Na⁺ gradient. For example, active lactose transport, mediated by lactose permease, is coupled to the influx of a proton into the bacterial Cell. This transport process is driven by the proton-motive force generated by electron transfer along the Respiratory Chain. Bacteria also exhibit another type of transport, namely group translocation, in which the solute is chemically modified during its transfer. Thus, the sugar-transporting phosphotransferase system phosphorylates sugars (e.g., converting glucose to glucose-6-phosphate) as they enter The Cell. The phosphoryl group donor in this process is phosphoenolpyruvate. Phosphorylation is mediated by three distinct Enzymes and a small phosphoryl-carrier protein (HPr).

Prokaryotic and Eukaryotic cells also contain Water-filled channels through which ions and small polar molecules can passively diffuse across membranes. For example, the outer membranes of Gram-negative bacteria contain porin channels about 10 Å in diameter. Gap Junctions are frequently found between adjacent cells of higher organisms. Through these channels, which are 20 Å in diameter, ions and most metabolites (such as Monosaccharides, amino acids, and NUCLEOTIDES) can pass freely from one cell to another. Gap junctions are closed in response to elevated Ca²⁺ levels. These intercellular channels play a vital role in cell-to-cell communication.

Transport Antibiotics increase membrane permeability to specific ions by functioning either as mobile carriers (e.g., valinomycin) or as channel formers (e.g., gramicidin A). A mobile-carrier antibiotic molecule, shaped like a shell, binds a metal ion within its central cavity. Thanks to its hydrophobic exterior, the entire complex is able to traverse the internal hydrocarbon core of the membrane. Channel-forming antibiotics create water-filled pores that span the membrane.