The effects of oxygen concentration on porphyrin biosynthesis in chicken-erythrocyte preparations.

In the biosynthesis of haem pigments, the concentration of oxygen appears to play a regulatory role at the sites of specific reactions in the pathway. The release of iron from storage in liver ferritin (Green & Mazur, 1956) and the catalysis, by soluble liver ferrochelatase preparations, of the incorporation of Fe2+ ions into protoporphyrin to form haem (Porra & Jones, 1963) are both favoured by anoxic conditions. There is considerable evidence that oxygen concentration controls the rate of synthesis of the porphyrin nucleus itself. In avian erythrocytes, oxygen is necessary for the conversion of acetate and glycine into 8-aminolaevulic acid (Gibson, Laver & Neuberger, 1958) and of coproporphyrinogen III into protoporphyrin IX (Falk, Dresel & Rimington, 1953; Granick & Mauzerall, 1958; Sano & Granick, 1961; Porra & Falk, 1961). These requirements for oxygen explain the rise, towards an optimum oxygen concentration of about 7 % (v/v), found by Falk, Porra, Brown, Moss & Larminie (1959) for the rate of formation of protoporphyrin from glycine; the decreases found at oxygen concentrations higher than 7 % have now been studied further. By the use of preparations from washed chicken erythrocytes that had been haemolysed, the inhibition by higher oxygen concentrations has now been traced to a reversible inhibition by oxygen of the rate of conversion of porphobilinogen into uroporphyrinogen III. These findings are discussed in relation to the known effects of oxygen concentration on haemopoiesis in higher animals and on the cytochrome concentrations in certain micro-organisms.