Brain 5-aminolaevulinate synthase. Developmental aspects and evidence for regulatory role

1. Brain 5-aminolaevulinate synthase showed a peak of increased activity in the first few weeks of life, which preceded and accompanied the development of brain cytochromes. 2. In the brain of the adult rat the activity of the enzyme was only 20% of that in the liver (on a per g wet wt. basis), but it was still probably sufficient to maintain the turnover of brain cytochromes. 3. The brain synthase activity could be decreased by treatment of rats with cycloheximide or with large doses of 5-aminolaevulinate, especially when this precursor was given as the methyl ester. 4. Injected haematin and CoCl2 markedly inhibited the synthase activity in the liver but failed to affect the brain enzyme; neither was taken up by the brain in vivo. 5. It is concluded that the brain can itself produce the haem required for the synthesis and turnover of its own haemoproteins and that 5-aminolaevulinate synthase may regulate the pathway in brain as in other tissues. 6. The relevance of the present findings to the pathogenesis of the neurological symptoms of acute porphyria and to the beneficial effect of exogenous haematin in porphyric patients is briefly considered.