Organic functional groups, metabolic

Kalgutkar, A.S., Gardner, I., Obach, R.S. et al. (2005) A comprehensive listing of bioactivation pathways of organic functional groups. Current Drug Metabolism, 6, 161-225. 

While the enzymes involved in detoxication processes are nonspecific in the classical sense of intermediary metabolism, they often have distinct specificities both for organic functional groups and for the electronic, steric, and stereochemical environments where these functional groups are located. Enzyme specificity based on organic functional groups and their environments leads to a wide diversity in the alkaloid substrates possible and therefore the products obtained from biotransformation. This section of the chapter will concentrate principally on the enzymes themselves, including general concepts of substrate specificity and mechanism. 

Testa and Cruciani (2001) divided molecular factors into the effects of global properties of the molecule as a whole, such as solubility characteristics (the octanol-water partition coefficient) or molecular size. These determine distribution within an organism and proximal molecular factors such as substituents or chemical functionality that modify the rate of functional group metabolism (e.g., changes in local electron densities or MO energies). 

Metabolic Activation of Organic Functional Groups Utilized in Medicinal Chemistry... 

WE HAVE NOW studied the structures and typical reactions of the major types of organic functional groups. Further, we have examined the structures of carbohydrates, amino acids and proteins, nucleic acids, and lipids. Now let us apply this background to the study of the organic chemistry of metabolism. In this chapter, we study three key metabolic pathways glycolysis, the citric acid cycle, and the /3-oxidation of fatty acids. The first is a pathway by which glucose is converted to pyruvate and then to acetyl coenzyme A. The second is a pathway by which the hydrocarbon chains of fatty acids are degraded, two carbons at a time, to acetyl coenzyme A. The third is the pathway by which the carbon skeletons of carbohydrates, fatty acids, and proteins are oxidized to carbon dioxide. 

Those of you who go on to courses in biochemistry will undoubtedly study these metabolic pathways in considerable detail, including their role in energy production and conservation, their regulation, and the diseases associated with errors in particular metabolic steps. Our concern in this chapter is more limited. Our goal is to show that the reactions of these pathways are biochemical equivalents of organic functional group reactions we have already... 

It is hoped that these volumes will be useful not only to the chemist who wishes to carry out synthesis in the steroid field, but also to the broader group of organic chemists who are interested in carrying out selective and stereo-chemically defined reactions, as well as protective chemistry on extraneous functional groups, during a broad range of synthetic applications. The chapter on the introduction of deuterium and by inference tritium into steroids was included because of the importance of this technique in mechanistic and metabolic studies both in the steroid and nonsteroid field. 

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