Regulation by turnover of Na,K-ATPase in HeLa cells.

As in most if not all animal cells, HeLa Na,K-ATPase is an essential enzyme of the cell surface. The three ways, referred to in the Introduction, in which it is regulated may be summarized as follows: 1) The activity of the enzyme under normal conditions responds almost linearly to small perturbations in internal (Na+); this is short-term regulation. 2) In the normal steady state, the enzyme is one of the rapidly turning over components of the cell surface; this is part of long-term regulation. The functional importance of turnover to cell homeostasis depends on the reversibility of any event that may inactive the enzyme. Thus turnover is an important, but not the only, means of recovery from ouabain intoxication, and for an inactivating ligand that dissociates more readily than ouabain turnover may be relatively unimportant. Conversely, turnover may be the only means of recovery from thermal inactivation at physiological temperatures. 3) Under conditions of prolonged stress, turnover itself may be modulated so as to enhance the number of active enzymes on the cell surface. Regulation by turnover has the advantage of permitting a prompt response to a changing cell environment, whereas regulation by synthesis would introduce a delay in response at least equal to the transit time. Broadman et al [1974] have suggested that the signal for the increase in Na,K-ATPase is elevated cellular (Na+), but how this is translated into a mechanism for altering the specific clearance of this enzyme from the membrane is not known.