Studies on phytoenzymes as mimics of mammalian drug metabolising enzymes

Abstract

Drug metabolism and pharmacokinetics is an integral part of the drug discovery and development process. The pharmacokinetic (absorption, distribution, metabolism and excretion) properties of a drug allow the drug development scientist to understand the safety and efficacy data required for regulatory approval. Further, the knowledge of mammalian enzymes involved in the metabolism of a new chemical entity is of prime importance. In this regard, plant metabolism of organic compounds is similar to the mammalian metabolism in terms of the processes for detoxification of contaminants, the specific enzymatic pathways, the structure of the enzymes involved and the removal of the compounds from the susceptible organelles. In our studies, we isolated phytoenzymes (esterases and glutathione-Stransferases, GSTs) from plant cells and investigated their applicability as tools for drug metabolism studies. A total of 32 plants were screened for esterases activity and 14 plants for GSTs activity. In case of esterases, the activity was compared to human plasma esterases and also the effect of esterase inhibitor on the activity was studied. Overall, the presence of phytoenzymes and their catalytic similarities to the mammalian drug metabolising enzymes suggest that plants can be potential models for mammalian drug metabolism. Further, phytoenzymes can be considered as a potential surrogate for reducing the number of animals utilized in the drug discovery process.