The influence of intracellular pH (pHi) on the energy metabolism during hypoxia was studied in the lugworm Arenicola marina using in vivo 31P nuclear magnetic resonance (NMR) spectroscopy and biochemical analysis of the metabolic end products during hypoxia. By addition of phenylphosphonic acid (PPA) to the incubation medium to increase the extracellular H + buffering capacity, different degrees of intracellular acidosis during hypoxia could be attained.At low extracellular PPA concentrations pHi dropped within 1 2 h of hypoxia from 7.3 to 6.7. High extracellular PPA concentrations (50 mM) kept pHi stable at 7.2. Glycogenolysis was enhanced during hypoxia at high pHi, as shown by the measured amounts of accumulated end products. ATP production at high pHi was 31 pmol/g h vs. 15 at low pHi. The mobilisation of the phosphagen phosphotaurocyamine (PTC) was, in contrast, decreased at high pHi: the ratio PTC/p-ATP dropped from 4.8 (normoxia) to 2.8 at high vs. 1.3 at low pHi. The reduction of the metabolic rate during hypoxia hence depends on intracellular acidosis: the rate of the Embden-Meyerhof-Parnas pathway at high pHi was 4.5 kmol/g h vs. 1.9 at low pHi.The lugworm Arenicola marina lives in the tidal zone of the sea coast, where during low tide it regularly has to cope with prolonged periods of environmental hypoxia. During hypoxia the energy demand is largely compensated by anaerobic ATP production particularly due to the degradation of aspartate and glycogen to alanine, strombine, acetate, and propionate (Schottler et al., '84; Siegmund et al., '85). The rate of anaerobic energy production, however, is not constant during prolonged periods of hypoxia. It decreases within 24 hours from 40 pmol ATP/h g dry weight to 9 pmol/h g dry weight (Schottler, '86).Such a reduction in ATP production and consumption has been observed in several animals which are able to survive prolonged periods of hypoxia (for review see Gade, '83; Storey, '85a) and it might be an important strategy for saving energy stores and preventing poisoning due to the accumulation of metabolic end products during hypoxia (cf. Hochachka, '86).Our knowledge about the mechanisms regulating the reduction of energy production and consumption are very sparse (cf. Hochachka and Somero, '84; Hochachka and Guppy, '87; Wegener, '88). Due to the general relevance of pH on enzyme activity, a decrease of intracellular pH has been related with the inhibition of the various metabolic pathways during hypoxia (for a review, cf. Roos and Boron, '81; Nuccitelli and Heiple, '82). Studies on the regulatory enzyme of glycolysis, phosphofructokinase (PFK), concerning the flux through the Embden-Meyerhof-Parnas (EMP) pathway evidenced a drastic reduction of the enzyme's activity when pH decreased (Ui, '66; Ebberink, '82). Other findings on molluscs imply that a drop in fructose 2,6-bisphosphate concentration (Storey, '85b) or that a covalent modification of PFK prevents the activation of this enzyme and thereby a Pasteur effect (Storey, '84). Preliminary in v...