High delta-aminolevulinic acid uptake in rat cerebral cortex: effect on porphyrin biosynthesis.
The response of nerve cells to high exogenous aminolevulinic acid (ALA) concentrations was studied by examining the changes in its uptake and in porphyrin biosynthesis. ALA was shown to be taken up by cerebral cortex particles by a non-saturable process. As opposed to other previously described experimental systems, it was also observed that 84-87% of porphyrins formed was found within the cells. Exposure of cerebral cortex particles to high exogenous ALA (0.8-4.0 mM) showed that ALA can be accumulated in relatively high concentrations in brain cells (21.04 +/- 1.05 nmol/mg protein). Under these experimental conditions, porphyrin biosynthesis was found to be markedly inhibited (52%). 2.4 mM ALA caused an initial stimulation of glucose uptake after 1 hr incubation and a later fall to below control values, being consistent with the fact that acute porphyric crisis could be precipitated by the action of ALA on energy metabolism. ALA toxicity could be due both to its accumulation in the cells and to deficient heme concentrations, with an additional effect on glucose metabolism. These findings provide the basis for a useful brain tissue model to investigate the nature of the metabolic mechanisms occurring in acute intermittent porphyria (AIP) patients.
Juknat
A A
AA
Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP) (CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Kotler
M L
ML
Batlle
A M
AM
D000622:Aminolevulinic Acid / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005947:Glucose / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D011166:Porphyrins / Q000096:biosynthesis*; D051381:Rats; D013050:Spectrometry, Fluorescence
D011166:Porphyrins; D006418:Heme; D000622:Aminolevulinic Acid; D005947:Glucose