鉛中毒におけるPorphobilinogenについて

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Lead poisoning is associated with characteristic urinary increases of δ-aminolevulinic acid and coproporphyrinogen III, elevated erythrocyte protoporphyrin concentration and partial block of δ- aminolevulinic acid dehydratase.
In human lead poisoning a very small amount of increase of porphobilinogen and uroporphyrinogen III is reported, while in rabbits porphobilinogen increases but uroporphyrinogen III does not as in the human cases. The small amount of porphobilinogen or uroporphyrinogen III in the human urine may be explained by δ-aminolevulinic acid dehydratase inhibition, but the increase in coproporphyrinogen III is as yet inexplainable.
An alternative pathway of coproporphyrinogen III formation from δ-aminolevulinic acid or porphobilinogen has and suggested in lead poisoning. We proposed that an intermediate, 2-amino-methyl-3-methyl-4-carboxyethyl-pyrrole, may be formed in vivo by enzymic condensation of δ-aminolevulinic acid and 1-amino-butane-2-one (β-ketobutylamine) or by prior decarboxylation of acetic acid sidechain of porphobilinogen. To test this hypothesis we made an experiment, the results of which are as follows.
The pyrrole compounds were isolated from the urine or the incubation mixture with δ-aminolevulinic acid and tissue homogenates (bone marrow, liver and kidneys) of lead poisoned rabbits by using the column chromatography on Dowex 2. All the pyrrole compounds were further converted to porphyrins by chemical condensation technique, resulting in the formation of the mixture of uroporphyrin isomers, though no coproporphyrin was detected.
The results indicate that the pyrrole compounds in lead poisoning are identical with authentic porphobilinogen and the prior decarboxylation of porphobilinogen appears unlikely. It is suggested that the increase of coproporphyrinogen III in lead poisoning may be caused by over-production of δ-aminolevulinic acid. The increased amount ofthe precursor seems to overcome the partial blocking of δ-aminolevulirlic acid dehydratase and thenormal rate of porphyrin synthesis may be formed.