Biogenesis of mitochondrial proteins. Regulation of production of δ-aminolaevulinate synthase by haemin in embryonic-chick liver

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Abstract
The effect of hemin on the biogenesis of .delta.-aminolevulinate synthase (ALA synthase) was investigated in primary cultures of embryonic-chick liver. The activity of the enzyme and the amount of the enzyme detected by immune-blotting were determined in hepatocytes incubated with the porphyrogenic agent allylisopropylacetamide. The loss in ALA synthase activity in cells incubated in the presence of hemin (10 .mu.M) was roughly proportional to a loss in the immune-reactive mass of the enzyme. Hemin was as effective as cycloheximide in causing depletion of ALA synthase in hepatocytes. Hemin blocks the maturation of the precursor of ALA synthase. Results on analyses of immune-precipitated ALA synthase after pulse-labeling with [35S]methionine in the presence and in the absence of hemin showed that the inhibition of processing of pre-ALA synthase in cells by hemin was concentration-dependent. A concentration of 2 .mu.M in the culture medium blocked the processing of pre-ALA synthase by 50% in hepatocytes. After inhibition of its maturation by hemin, pre-ALA synthase turned-over with a half-time of 30 min; mature ALA synthase turned-over with a half-time of 120 min.

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