EARLY EVIDENCE FOR OXIDATIVE PHOSPHORYLATION

We have already mentioned Lundsgaard's observation (3) in 1930 that with iodoacetate-poisoned muscle, no longer able to carry on glycolysis, there was clear evidence of aerobic resyn thesis of phosphocreatine during or after its breakdown in contraction. About the same time we find Engelhardt's study of oxidative phosphorylation in isolated red blood cells, the forerunner of studies still continuing on the mechanism of this phosphorylation in cell-free preparations and purified enzyme systems. In Engelhardt's experiments (4, 5) erythrocytes from mammals and birds were used in presence of glucose, and of fluoride to prevent glycolysis. In conditions of vigorous respiration of the suspension, inorganic phosphate was taken up with formation of pyrophosphate. In a period of anaerobiosis, pyrophosphate broke down; on re-admission of oxygen there was increased oxygen consumption, pyrophosphate synthesis paralleling the rate of extra oxygen uptake and levelling off with it. It is clear from Engelhardt's discussion (5) that he considered this pyrophosphate to be contained in ATP, and he adumbrated an interesting conception of metabolic cycles in which breakdown products act as stimulants of resynthetic processes.

The next contribution was from Kalckar (2) in 1937, using kidney-cortex extracts. In this tissue there is no phosphate uptake accompanying glycolysis, as there is in muscle extracts, but aerobically in presence of fluoride he found that for every mole of oxygen used, about 1 mole of phosphate was esterified. Adenylic acid was converted to ATP, and glucose, fructose or fructose-6-phosphate could be phosphorylated.