Surface binding hypothesis

Here we suggest that ions or molecules temporarily bound to the membrane surface may have their transmembrane movement enhanced by pore formation and that this possible mechanism also has catalytic features. This additional hypothesis envisions that local membrane conformational changes can result from both the local transmembrane voltage and the surface binding of a transported molecule (S). That is, a pore-substrate complex is formed. One possible outcome is transmembrane transport in which S is temporarily bound to the inner surface of a pore, with subsequent electrical lateral motion (relative to the pore inner surface) by diffusion or lateral drift to the other side. Alternatively, as a pore shrinks and closes, S is presented to the other side of the membrane. In either case, upon dissociation, transport of S will have been accomplished. 

The initial steps in enzyme-catalysed reactions involve the binding of the reactants to the enzyme surface and one of the functions of the enzyme is to orientate these reactants relative to each other. This idea was suggested by Fischer as a lock-and-key hypothesis, where the enzyme is the lock and the... 

An old hypothesis is based on the observations of Dahlen et al. (D3), who demonstrated that above a certain concentration in plasma, Lp(a) could bind to glycosaminoglycans in the arterial wall (B12). Colocalization of Lp(a) and fibrin on the arterial wall can lead to oxidative changes in the lipid moiety of Lp(a) and induce the formation of oxidatively modified cholesterol esters, which in turn can influence the interaction of Lp(a) and its receptors on macrophages. This process is promoted by the presence of calcium ions. Cushing (C14), Loscalzo (L22), and Rath (R3) reported a colocalization of undegraded Lp(a) and apo-Bl00 in the extracellular space of the arterial wall. In contrast to LDL, Lp(a) is a substrate for tissue transglutaminase and Factor XUIa and can be altered to products that readily interact with cell surface structures (B21). 

Requisite to this conclusion is the hypothesis of these authors that the enzyme. . is so oriented within the endoplasmic membrane that the active binding sites for glucose-6-P are predominantly on the outer surface of the microsomes that is readily accessible to the cytoplasm of the cell, while the sites for glucose are largely on that inner surface which corresponds to the space between the ergastoplasmic membranes and are, in effect, outside of the cell. (90)... 

The location of the acyl chain is of primary importance in the binding process because of its size. Due to the movement of lid during interfacial activation, a hydrophobic trench is created between the lid and enzyme surface. The trench size is ideal to accommodate the acyl chain. Interactions between the non-polar residues of the trench and the non-polar acyl chain stabilize the coupling. It has been postulated that the configuration of the trench is responsible for substrate specificity. This hypothesis seems plausible since lipases usually discriminate against certain acyl chain lengths, degrees of unsaturation, and location of double bonds in the chain. Any of these factors could affect the interaction between the acyl chain and the trench. 

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