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Our review of the metabolic pathways of pyridines and aza-arenes showed that biodegradation of heterocyclic aromatic compounds occurs under both aerobic and anaerobic conditions. Depending upon the environmental conditions, different types of bacteria, fungi, and enzymes are involved in the degradation process of these compounds. Our review indicated that different organisms are using different pathways to biotransform a substrate. Our review also showed that the transformation rate of the pyridine derivatives is dependent on the substituents. For example, pyridine carboxylic acids have the highest transformation rate followed by mono-hydroxypyridines, methylpyridines, aminopyridines, and halogenated pyridines. Through the isolation of metabolites, it was possible to demonstrate the mineralization pathway of various heterocyclic aromatic compounds. By using 14C-labeled substrates, it was possible to show that ring fission of a specific heterocyclic compound occurs at a specific position of the ring. Furthermore, many researchers have been able to isolate and characterize the microorganisms or even the enzymes involved in the transformation of these compounds or their derivatives. In studies involving 18O labeling as well as the use of cofactors and coenzymes, it was possible to prove that specific enzymes (e.g., mono- or dioxygenases) are involved in a particular degradation step. By using H2 18O, it could be shown that in certain transformation reactions, the oxygen was derived from water and that therefore these reactions might also occur under anaerobic conditions.