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Excretion of porphyrins in urine and bile after the administration of delta-aminolevulinic acid.

Excretion of porphyrins into bile and urine after intravenous injection of delta-ALA was studied in three patients with catheters inserted into the bile duct because of biliary obstruction and in two healthy volunteers. Excretion of porphyrins into bile increased in response to increasing doses of delta-ALA--up to 18 mumol/kg. On the other hand, excretion into urine reached a constant rate at 2 to 4 mumol/kg delta-ALA and did not increase further with larger doses. These findings suggest that transport of porphyrins across the liver cell membrane to the blood must be an important factor in determining the rate of excretion into the urine. After administration of delta-ALA,excretion of coproporphyrin III into urine increased more than that of coproporphyrin I. As a result, the former was the predominant form of urinary coproporphyrin. When radioactive delta-ALA was administered intravenously, far greater radioactivity was recovered in urine as coproporphyrin III than as coproporphyrin I. These results indicate that only a small portion of urinary coproporphyrin I is derived from the liver. A possible source of coproporphyrin I may be erythropoietic tissues, since the amount of urinary coproporphyrin I was considerably decreased in patients with severely suppressed erythropoiesis.

Aminolevulinic Acid↗

Relationships between three indicators of lead exposure in workers: blood lead, delta-aminolevulinic acid and free erythrocyte protoporphyrin.

Whole blood lead (Pb-B), urinary delta-aminolevulinic acid (ALA-U) and free erythrocyte protoporphyrin (FEP) were measured in three groups of workers (n = 196) with different degrees of exposure to lead, and one group of men with no previous exposure to the metal (n = 48). Inter-group comparison showed a correlation of r = 0.73 between Pb-B and log of ALA-U, and r = 0.91 between Pb-B and log of FEP. ALA-U and FEP values rose sharply after Pb-B values reached 450-500 micrograms/l.

Adolescent↗

Determination of 5-aminolevulinic acid in biological samples by high-performance liquid chromatography.

5-Aminolevulinic acid (ALA), the common precursor of all naturally occurring tetrapyrroles, forms a stable condensation product with 2-amino-3-hydroxynaphthalene which can be identified by its fluorescence. Separation of the compound by reversed-phase high-performance liquid chromatography on RPC-18 columns allows its detection down to the picomolar range and can be successfully applied for ALA analysis in small biological samples. The reaction product of ALA with 2-amino-3-hydroxynaphthalene has been synthesized and characterized.

Aminolevulinic Acid↗

Production of delta-aminolevulinate: subcellular localization and purification of murine hepatic L-alanine: 4,5-dioxovaleric acid aminotransferase.

1. L-Alanine: 4,5-dioxovaleric acid aminotransferase (DOVA transaminase) activity was measured in murine liver, kidney and spleen homogenates. 2. Among the organs examined, the specific activity of the enzyme was highest in kidney, followed by liver then spleen. 3. No differences in DOVA transaminase activity in kidney, liver and spleen homogenates were detected between mouse strains C57BL/6J and DBA/2J. 4. Based on enzyme activity, the capacity of DOVA transaminase to catalyze the formation of delta-aminolevulinic acid (ALA) in liver appeared much greater than the capacity of ALA synthase. 5. In DBA/2J animals, DOVA transaminase activity in liver mitochondrial fractions prepared by differential centrifugation was 24 nmol ALA formed/hr/mg protein compared with 0.63 nmol ALA formed/hr/mg protein for ALA synthase. 6. Cell fractionation analyses indicated that liver DOVA transaminase is located in the mitochondrial matrix. 7. The liver enzyme was purified from mitoplasts by chromatography on DEAE-Sephacel followed by affinity chromatography on L-alanine-AH-Sepharose. 8. The specific activity of the purified DOVA transaminase was 1600 nmol ALA formed/hr/mg protein. 9. The yield of the purification was ca 90 micrograms of protein per gram liver wet weight. 10. The purified enzyme had a subunit mol. wt of 146,000 +/- 5000 as determined by electrophoresis under denaturing conditions.

Aminolevulinic Acid↗

Melatonin counteracts the 5-aminolevulinic acid-induced rise of rat forebrain tryptophan and serotonin concentrations at night.

When rats were exposed to extended light into the normal dark phase, the administration of 5-aminolevulinic acid (5-ALA) markedly stimulated the accumulation of tryptophan (TRP) and the synthesis of serotonin (5-HT) in the forebrain. When a single injection of melatonin (25 micrograms) was given near the end of the 5-ALA treatment, the rise in forebrain TRP levels was either totally prevented or reversed; likewise, the increased levels of 5-HT were also suppressed. Melatonin by itself also slightly suppressed forebrain TRP levels in non-5-ALA-treated rats. Whether these are pharmacological or physiological effects of melatonin remains to be determined.

Aminolevulinic Acid↗