FUNCTIONALIZATION AND CONJUGATION AS DRUG METABOLISM PATHWAYS: INDIVIDUAL REACTIONS AND A LOOK AT ON COMPROMISING FACTORS: A REVIEW
JUSTIN N. KABERA *
College of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China and National Industrial Research and Development Agency, Kigali, Rwanda
ALLY R. MUSSA
College of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
EDMOND SEMANA
College of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
YANG FAN
College of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China
HE XIN
College of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China and Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin, China
*Author to whom correspondence should be addressed.
Abstract
Drug metabolism pathways are the chemical processes generally in two phases: Phase I known as functionalization and Phase II as conjugation. The reactions of Phase I include oxidation, reduction, and hydrolytic reactions; they introduce a functional group that make the drug more polar. Phase II reactions are those in which an endogenous compound such as glucuronic acid or glutathione combine with functional group derived from phase I to produce a highly polar drug conjugate. These reactions constitute a domain where biochemists and pharmacologists collaborate in the search of new drug entities (NDEs), so they are a basic understanding of the role of the chemistry in the biotransformation of drug in the body. This review is aimed to highlight the individual biochemical reactions and their mechanism involved in drug metabolism, metabolizing enzymes and the affecting factors that could compromise the processes: genetic, environmental and physiological factors. These reactions, although have been discovered long ago, they continue to be exploited in drug development and will still lead the design of medicines for better bioavailability.
Keywords: Functionalization, conjugation, drug metabolism, CYP450, affecting factors