Coordination of metabolism and intracellular acid–base status: ionic regulation and metabolic consequences

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Abstract
This review discusses the mechanisms by which animal cells regulate intracellular pH (pHi), the variations in pHi encountered in vivo, and the impact that variations in pHi (and other acid–base variables) have on metabolism. Cells regulate pHi by a combination of (i) physicochemical buffering by intracellular components; (ii) transport of acids and bases across the plasma membrane; and (iii) production and consumption of acids and bases by metabolism. Ionic transport is by far the best studied of these three mechanisms, and several specific plasma membrane exchangers (e.g., Na+–H+ exchange) are important regulators of pHi The precise quantitative contribution of the other two mechanisms to pHi regulation awaits further study. Intracellular pH variations in vivo can be substantial (i.e., up to 1 unit in some cases) and can lead to marked changes in metabolism. Furthermore, changes in carbon dioxide tension and bicarbonate concentration can also affect metabolism. Catecholamines appear to be important regulatory signals in metabolic compensation for acid–base perturbations, but in some cases acid–base disturbances may produce adaptive metabolic changes directly.

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