The metabolism of δ-aminolaevulic acid. 1. Normal pathways, studied with the aid of 15N

Abstract

(N15) Aminolaevulic acid (ALA) was fed or administered parenterally to normal human subjects and to rats. Incorporation of N15 into the heme of the circulating hemoglobin of rats was 6 to 7 times less than reported for an equivalent amount of (N15) glycine. Administration of (N15) ALA produced labeling in the urinary urea to approximately the same extent as (N15) glycine, but the latter was much more efficient as a precursor of hippuric acid than the former. (N15) ALA also gave rise to significant labeling in the amide groups of liver proteins. Since a large proportion of the ALA was excreted unchanged in the urine, both in man and in the rat within a few hours of administration, ALA is apparently poorly reabsorbed, if at all, by the tubules of the kidney. Most of the N15 present in the urine was in the fraction remaining after removal of urea and NH3, and must be presumed to have been mainly in the form of unchanged ALA. In almost all experiments the N15 concentration in the urinary NH3 was considerably greater than in the urea, even after 2 days. Administration of ALA to man or rat has been found to give rise to excretion of appreciable amounts of porphobilinogen (PBG) in the urine. Conversion of ALA into PBG increased with the dose level up to a maximum. Administration of ALA to human subjects produced skin reactions suggesting photo-sensitization. The bearing of this experimentally induced sensitivity on the explanation of the clinical condition associated with congenital porphyria is discussed.