Studies on the induction of hepatic δ-aminolevulinic acid synthetase in rat liver mitochondria

Abstract

Administration of allylisopropylacetamide (AIA) to rats caused an initial induction of hepatic δ-aminolevulinic acid (ALA) synthetase activity in the postmitochondrial supernatant fraction of the cell. The activity in this fraction decreased 50% from 1–3 hr after injection, while during this time period, the ALA synthetase activity of the mitochondrial fraction continued to increase at a nearly linear rate. Cycloheximide blocked the induction of ALA synthetase in both subcellular fractions. Two injections of chloramphenicol inhibited 50–60% the induction of ALA synthetase activity in the mitochondrial fraction but not in the postmitochondrial supernatant fraction. The apparent half-life of the enzyme was 66 min after cycloheximide administration and 118 min after chloramphenicol administration. A slower rate of turnover of the enzyme was observed in animals 1 hr after AIA injection. These results support the suggestion that ALA synthetase is synthesized in the microsomes and is transferred to the mitochondrial matrix in a subsequent step. The content of cytochromes a–a 3, b, c–c 1 was increased 50% in mitochondria which contained high ALA synthetase activity.