Regulation of heme synthesis in the regenerating rat liver (original) (raw)

1990, Biochemical Medicine and Metabolic Biology

Various aspects of heme metabolism in the regenerating rat liver have been documented (l-9), but no clear-cut picture has emerged giving an overview of the regulation of heme synthesis in regenerating rat liver. The activity of 6aminolevulinic acid synthase (ALAS) (EC 2.3.1.37) (2,5,6,9) and the concentrations of cellular heme and of P450 (1,2,5,9) were both reported to be reduced. One may, therefore, assume that in the postoperative state, ALAS activity is not under the control of its end product heme. However, changes in cellular heme, as measured by the "hot oxalic" method or by employment of pyridine hemochromogen, do not necessarily reflect the concentration of the "free heme" in the regulatory heme pool (10). The latter, which constitutes only a small percentage of intracellular heme, is considered, rather than total heme content, to be the regulator of ALAS (1 l-l 3). This work was carried out in order to provide data concerning the "regulatory heme pool" in regenerating rat liver and to further investigate whether the control of ALAS in this system differs from that of normal liver. MATERIALS AND METHODS Methods Ruts. Male Wistar rats, bred at random and weighing 140-160 g, were subjected either to sham operation (laparatomy only) or to two-thirds hepatectomy as described by Higgins and Anderson (14). On the appropriate days, rats were killed, livers were removed, and the various determinations were carried out. Experimental porphyria was induced by two ip injections (24-hr interval between injections) of either diethoxycarbonyl dihydrocollidine (DDC) or allylisopropylacetamide (AIA), 400 mg/kg/day dissolved in dimethyl sulfoxide (DMSO) (0.2 ml of 350 mg/ml). Operations were performed on the first or second day of drug administrations. Animals were fasted from 24 hr before the first injection until 24 hr after the second injection. Control rats were injected with DMSO only.