Metabolism in the Rat of Some Pyrazine Derivatives having Flavour Importance in Foods

Abstract

1. The metabolism of several alkyl- and alkoxy-substituted pyrazines in the rat has been investigated. 2. Alkyl substituted compounds were oxidized to the corresponding acids which were excreted in the urine as such or as their glycine cojugates. The extent of oxidation was reduced when two adjacent alkyl groups were present. In the latter case ring hydroxylation also occurred. Methoxy-substituted pyrazines underwent O-demethylation and ring hydroxylation. 3. Little or no biliary excretion of the pyrazines or their metabolites occurred. 4. Some preliminary results on the metabolism of 2-isobutyl-3-methoxy-pyrazine (the major characteristic flavour component of bell pepper) have been obtained. 5. For comparative purposes the metabolism of some similarly substituted pyridines was investigated.

Scientific Opinion on Flavouring Group Evaluation 17, Revision 2 (FGE.17Rev2): Pyrazine derivatives from chemical group 24

“…Approximately 90 -100 % of a 100 mg/kg dose of 2-methylpyrazine, 2,5-dimethylpyrazine, 2,6-dimethylpyrazine or 2-methoxypyrazine administered to male Wistar rats by stomach tube was excreted in the urine as polar metabolites within 24 hours. Also, 50 % of the orally administered dose of 100 mg 2,3-dimethylpyrazine kg was recovered in the urine within 24 hours (Hawksworth & Scheline, 1975).…”

“…In rats, orally administered substituted pyrazines are absorbed from the gastrointestinal tract and excreted (Hawksworth & Scheline, 1975). Approximately 90 -100 % of a 100 mg/kg dose of 2-methylpyrazine, 2,5-dimethylpyrazine, 2,6-dimethylpyrazine or 2-methoxypyrazine administered to male Wistar rats by stomach tube was excreted in the urine as polar metabolites within 24 hours.…”

“…For example, 2,5-dimethylpyrazine and 2,6-dimethylpyrazine are oxidised in rats almost exclusively via their aliphatic sidechains to carboxylic acid derivatives. Conversely, 2,3-dimethylpyrazine primarily undergoes ring hydroxylation, because side-chain oxidation is retarded (only 13 % of the administered dose oxidised) by the steric hindrance between the methyl groups (Hawksworth & Scheline, 1975).…”

“…In eight candidate substances the pyrazine ring is fused with either cyclopentane 14.102,14.113,and 14.161 Limited information has been submitted to describe the metabolism of the pyrazines and alkyl-, aryl-, or alicyclic-substituted pyrazines in this group of flavouring substances. Almost all data available come from one paper (Hawksworth & Scheline, 1975) and a few review papers (Beedham, 1985;Beedham, 1988;Parkinson, 1996a). Additional information provided in other papers is supportive of the metabolic conversions that have been described, but of little quantitative relevance as they concern substances that are widely different from the candidate substances in this group and the supporting ones evaluated by the JECFA.…”

“…For example, methyl-substituted pyrazines are oxidised to yield the corresponding pyrazine-carboxylic acids, which may be excreted as glycine conjugates (Hawksworth & Scheline, 1975). An alternative pathway for substituted pyrazines and primary pathway for pyrazine involves hydroxylation of the pyrazine ring (Hawksworth & Scheline, 1975;Whitehouse et al, 1987;Yamamoto et al, 1987a;Yamamoto et al, 1987b). For example, 2,5-dimethylpyrazine and 2,6-dimethylpyrazine are oxidised in rats almost exclusively via their aliphatic sidechains to carboxylic acid derivatives.…”