Figure 1.  How might DpH (interior alkaline) and DY (interior negative) drive accumulation of different substrates.  Shown is an idealized membrane vesicle pumping out protons by either the respiratory chain (at the top) or by ATP hydrolysis via F₁F_o-ATP synthase (at the bottom) and generating a DpH (interior alkaline; H+ inside is smaller than H+ outside) and a DY (interior negative; minus symbol inside).

 Accumulation of cations (C⁺; e.g., lysine, arginine) is postulated to occur by uniport via a trans­membrane protein (a.k.a., uniporter, transporter, carrier or permease) with specificity for a given cation allowing the cation to permeate the membrane and equilibrate with the DY (interior negative) across the membrane.  Accordingly, uniport of cations should be driven specifically by DY (interior negative). 

Accumulation of weak acids (A^–H⁺; e.g., lactate, succinate, glucose-6-phosphate) is thought to occur by a type of symport in which the protonated weak acid is translocated via a transmembrane protein with specificity for a given weak acid (a).  Once the weak acid is released inside, since internal pH is alkaline relative to outside pH, the weak acid dissociates and the anion accumulates against a gradient.  Accordingly, symport of weak acids should be driven specifically by DpH (interior alkaline), and the proton(s) is translocated across the membrane in association with its anion (i.e., the undissociated weak acid). 

Accumulation of neutral substrates (N; e.g., sugars, certain amino acids) occurs by a second type of symport (b) in which the neutral substrate and a proton(s) is translocated by a substrate-specific transmembrane protein.  In this case, the proton and the substrate occupy separate sites on the transport protein, and the free energy released by the energetically downhill translocation of protons with either DpH (interior alkaline) or DY (interior negative) is used by the symporter to drive the uphill accumulation of substrate. Accordingly, symport of neutral substrates should be driven by either DpH or DY. 

Extrusion of noxious substrates (X; e.g., sodium, calcium, tetracycline) against a concentration gradient occurs by antiport.  Again, the proton and the substrate occupy separate sites on a substrate-specific transmembrane protein, but in this case, the free energy released by the energetically downhill translocation of protons with either DpH (interior alkaline) or DY (interior negative) is used by the antiporter to drive the efflux of substrate against a concentration gradient. Accordingly, antiport should be driven by either DpH or DY.