Enzyme Regulation General

Dische The discovery of feedback inhibition Trends in Biochemical Sciences 1,269 (1976). 

Koshland, G. Nemethy, and D. Filmer Comparison of experimental binding data and theoretical models in proteins containing subunits Biochemistry 5,365 (1966). 

Changeux, and E Jacob Allosteric proteins and cellular control systems. Journal of Molecular Biology 6, 306 (1963). 

Changeux On the nature of allosteric transitions A plausible model. Journal of Molecular Biology 12, 88 (1965). 

Segal Enzymatic interconversions of active and inactive forms of enzymes. Science 180,25 (1973). 

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The theoretical analysis of the metabolic fate of PAC or xenobiotics in general demands a systems approach since individual components of the metabolic networks are closely linked via common substrates or cofactors as well as allosteric enzyme regulation [40, 41]. As shown in a later section, drug catabolites especially affect cell physiology and thereby greatly impinge on cellular drug action. 

There is some confusion in the literature about the use of the term "allosteric" for an enzyme. Many authors restrict this term to multi-subunit enzymes that show substrate cooperativity and sigmoidal kinetics. Other authors, however, are less specific and their definitions include enzymes that follow Michaelis- Menten kinetics and have non- or uncompetitive inhibitors. Fortunately, in metabolism, regulated enzymes are generally multi-subunit, cooperative, enzymes and fall into the more specific use of the term. 

A second method of enzyme regulation involves the combination of the enzyme with some other compound such that the three-dimensional conformation of the enzyme is altered and its catalytic activity is changed. Compounds that alter enzymes this way are called modulators of the activity they may increase the activity (activators) or decrease the activity (inhibitors). The noncompetitive inhibitors we studied in Section 10.7 are examples of modulators. Enzymes that have a quaternary protein structure with distinctive binding sites for modulators are referred to as allosteric enzymes. These variable-rate enzymes are often located at key control points in cellular processes. In general, activators act as signals for increased production, whereas inhibitors are used to stop the formation of excess products. 

The statement that not the compound itself but its biosynthetic route has the taxonomical sig ni cance may be still valid. However, we know already that the biosynthetic route consists of complex metabolomic process including the genomic constitution, gene expression, transcriptional and translational regulation, enzyme activities at different biosynthetic levels, interactions with transporters, translocation, and spatial isolation (Dudareva et al., 2006 Dinesh and Nagegowda, 2010). The result of the enzymatic reaction is determined not only by the availability and constitution of the enzyme but also by the availability of precursors and different interactions therefore, the simple presence or absence of a certain enzyme in general cannot determine the nal product. 

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