PORPHYRINOGENESIS IN RAT CEREBELLUM - EFFECT OF HIGH DELTA-AMINOLEVULINIC-ACID CONCENTRATIONS

1. delta-aminolevulinic acid (ALA) uptake as well as precursor accumul ation and porphyrin biosynthesis were investigated in rat cerebellum, using as experimental approach minimal tissue units called particles. 2. ALA was shown to be taken up into cerebellum particles by a non sat urable process up to 4.0 mM ALA whereas PBG and porphyrin formation ex hibited a hyperbolic response reaching the plateau at about 1.0 and 1. 5 mM ALA respectively. 3. Exposure of cerebellum particles to high exo genous ALA amounts (0.01-4.0 mM) indicated that ALA can be accumulated in relatively high concentrations in the cells (40 nmol/mg protein). Under these experimental conditions, PBG-D presented a low activity (3 .25 pmol/mg protein/4hr) showing to be a secondary control step in hem e biosynthesis. 4. Incubation of cerebellum particles in the presence of a physiological concentration of glucose revealed that 1.0 mM ALA d ecreased glucose uptake by the cells (87% during 1 hr incubation), bei ng consistent with the fact that acute attacks are precipitated by fas ting and that sugar administration appeared to be an efficient treatme nt of AIP crisis. 5. These findings provide the basis for a useful mod el to study the nature of the metabolic mechanism underlying the acute attack.