Reaction of Acetaldehyde with 5-Aminolevulinic Acid via Dihydropyrazine Derivative

• Published in: Chemical & pharmaceutical bulletin Vol. 63; no. 2; pp. 126 - 129
• Main Authors: Suzuki, Toshinori, Yasuhara, Naoki, Ueda, Takashi, Inukai, Michiyo, Mio, Mitsunobu
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 2015; Pharmaceutical Soc Japan; Japan Science and Technology Agency
• Subjects: 3,6-dihydropyrazine-2,5-dipropanoic acid; 3-ethylpyrazine-2,5-dipropanoic acid; 5-aminolevulinic acid; acetaldehyde; Acetaldehyde - chemistry; Acetaldehyde - toxicity; Aminolevulinic Acid - chemistry; Aminolevulinic Acid - pharmacology; Animals; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Chromatography, High Pressure Liquid; Dimerization; Drug Interactions; Drug-Related Side Effects and Adverse Reactions - prevention & control; Hydrogen-Ion Concentration; Lethal Dose 50; Life Sciences & Biomedicine; Male; Mass Spectrometry; Mice; Mice, Inbred ICR; Pharmacology & Pharmacy; Physical Sciences; Propionates - analysis; Propionates - chemistry; Propionates - metabolism; Pyrazines - analysis; Pyrazines - chemistry; Pyrazines - metabolism; Science & Technology; acetaldehyde; ALCOHOL; DELTA-AMINOLEVULINIC-ACID; 5-aminolevulinic acid; 3-ethylpyrazine-2,5-dipropanoic acid; 3,6-dihydropyrazine-2,5-dipropanoic acid
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.c14-00694

When a solution of 5-aminolevulinic acid (ALA) was incubated with acetaldehyde at neutral pH, a product was generated. This product was identified as 3-ethylpyrazine-2,5-dipropanoic acid (ETPY). ETPY was stable at neutral pH. It has been reported that ALA dimerizes at neutral pH generating 3,6-dihydropyrazine-2,5-dipropanoic acid (DHPY), and subsequently resulting in pyrazine-2,5-dipropanoic acid (PY) by autoxidation. In the present reaction, DHPY generated from ALA reacted with acetaldehyde, resulting in ETPY. Preadministration of ALA 3 min prior to acetaldehyde injection supressed the toxicity of acetaldehyde in male mice. These results suggest that ALA may be useful as a scavenger for acetaldehyde.