In a patient with a severe attack of acute intermittent porphyria, hematin given intravenously caused marked diminution of serum delta-aminolevulinic acid and porphobilinogen. The decline of aminolevulinate was more rapid than that of porphobilinoge. After 2 days of hematin administration, about 5 days were required for delta-aminolevulinic acid, and 11 days for porphobilinogen to return to the concentrations that were detected before treatment. Urinary excretion of both compounds also decreased after hematin administration. Considerable amounts of porphobilinogen were also found in the cerebrospinal fluid of the patient.

Adult↗

PubMed1971

Presynaptic neuromuscular inhibition by porphobilinogen and porphobilin.

The rat hemidiaphragm was studied in vitro as a test system to evaluate the effects of heme precursors and the uroporphyrins upon neuromuscular excitability. Porphobilinogen and porphobilin had no effect on the resting miniature end-plate potential frequency, but the K(+)-augmented frequency was significantly reduced. Porphobilin and porphobilinogen gave 50% of their maximal effect at concentrations of 0.008 and 0.6 mug/ml, respectively; the effect increased with concentration. Uroporphyrin I at 0.05-1.0 mug/ml caused a 25% decrease in frequency, but the effect did not increase with concentration. At similar concentrations, uroporphyrin III was without effect. The concentrations of porphobilin and porphobilinogen effective in inhibiting the K(+) stimulation, which are several orders of magnitude lower than the effective concentrations of simple amino acids, are those which might reasonably be expected in the sera of patients with acute intermittent porphyria.

Animals↗

PubMed1971

The absolute configuration of natural (-)-stercobilin and other urobilinoid compounds.

Chromic acid degradation of natural (-)-stercobilin (1) yields 2(R)-methyl-3(R)-ethylsuccinimide (+2), whereby the absolute configuration of 1 at the chiral centers C-1, C-2, C-7, and C-8 is established. The substituted oxo-tetrahydrodipyrromethane precursor, 5, for the total synthesis of (-)-stercobilins 3 and 4, in which the relative configuration between the asymmetric centers is known, yields 2(S)-methyl-3(S)-ethylsuccinimide (-2) under the same conditions of degradation. Nuclear magnetic resonance studies of 1 and 3 show that in 1 the hydrogen atoms at C-2 and C-2', as well as those at C-7 and C-7', are trans relative to one another. Accordingly, natural (-)-stercobilin possesses the 2'(S), 7'(S) configuration, and has the configuration formula 6(1 (R), 2(R), 2'(S), 7'(S), 7(R), 8(R)). These results, coupled with those of earlier studies, also establish the absolute configuration of the (+)-urobilin 7 and of the phycobilin 8 at C-7'.

Chromates↗

PubMed1971