Porphyrinogenesis in rat cerebellum. Effect of high delta-aminolevulinic acid concentration.

1. delta-Aminolevulinic acid (ALA) uptake as well as precursor accumulation 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 saturable process up to 4.0 mM ALA whereas PBG and porphyrin formation exhibited a hyperbolic response reaching the plateau at about 1.0 and 1.5 mM ALA respectively. 3. Exposure of cerebellum particles to high exogenous 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/4 hr) showing to be a secondary control step in heme biosynthesis. 4. Incubation of cerebellum particles in the presence of a physiological concentration of glucose revealed that 1.0 mM ALA decreased glucose uptake by the cells (87% during 1 hr incubation), being consistent with the fact that acute attacks are precipitated by fasting and that sugar administration appeared to be an efficient treatment of AIP crisis. 5. These findings provide the basis for a useful model to study the nature of the metabolic mechanism underlying the acute attack.