Enzyme regulation

Hundreds of metabohc reac tions take place simultaneously in cells. There are branched and parallel pathways, and a single biochemical may participate in sever distinct reactions. Through mass action, concentration changes caused by one reac tion may effect the kinetics and equilibrium concentrations of another. In order to prevent accumulation of too much of a biochemical, the product or an intermediate in the pathway may slow the production of an enzyme or may inhibit the ac tivation of enzymes regulating the pathway. This is termed feedback control and is shown in Fig. 24-1. More complicated examples are known where two biochemicals ac t in concert to inhibit an enzyme. As accumulation of excessive amounts of a certain biochemical may be the key to economic success, creating mutant cultures with defective metabolic controls has great value to the produc tion of a given produc t. 

Regulation of enzyme activity is achieved in a variety of ways, ranging from controls over the amount of enzyme protein produced by the cell to more rapid, reversible interactions of the enzyme with metabolic inhibitors and activators. Chapter 15 is devoted to discussions of enzyme regulation. Because most enzymes are proteins, we can anticipate that the functional attributes of enzymes are due to the remarkable versatility found in protein structures. 

FIGURE 15.2 Enzymes regulated by covalent modification are called interconvertible enzymes. The enzymes protein kinase and protein phosphatase, in the example shown here) catalyzing the conversion of the interconvertible enzyme between its two forms are called converter enzymes. In this example, the free enzyme form is catalytically active, whereas the phosphoryl-enzyme form represents an inactive state. The —OH on the interconvertible enzyme represents an —OH group on a specific amino acid side chain in the protein (for example, a particular Ser residue) capable of accepting the phosphoryl group. 

Specialized controls Enzyme regulation is an important matter to cells, and evolution has provided a variety of additional options, including zymogens, isozymes, and modulator proteins. 

Russell DW (2003) The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem 72 137-174... 

Ca2+-pumps. After entering the cell, Ca2+ is reversibly complexed to specific Ca2+-binding proteins that fiilfil multiple functions, including Ca2+-buffering and transport, activation of enzymes, regulation of contraction,... 

Weber G (editor) Advances in Enzyme Regulation. Pergamon Press, 1963 to the present. 

One main line of future research could be in the inhibitory/activating effect on key enzymes involved in the pathogenesis of arteriosclerosis. In particular, enzymes regulating signal transduction involved in phosphorylation of proteins, such as PKC and tyrosine protein kinase, seems to be somehow modulated by different polyphenols and may represent a possible target for polyphenol activity. 

In this section, the latest developments and recent publications on the biosynthesis of A9-THC and related cannabinoids as precursors are discussed. Special points of interests are the genetic aspects, enzyme regulation, and the environmental factors that have an influence on the cannabinoid content in the plant. Because of new and innovative developments in biotechnology we will give a short overview of new strategies for cannabinoid production in plant cell cultures and in heterologous organisms. 

Sartorelli AC, Agrawal KC, Tsiftsoglou AS, Moore EC (1977) Advances in Enzyme Regulation 15 117... 

Elledge SJ 1996 Cell cycle checkpoints preventing an identity crisis. Science 274 1664—1672 Evans EK, Kombluth S 1998 Regulation of apoptosis in Xenopus egg extracts. Adv Enzyme Regul 38 265-280... 

Talalay, P., A. T. Dinkova-Kostova, and W. D. Holtzclaw. 2003. Importance of phase 2 gene regulation in protection against electrophile and reactive oxygen toxicity and carcinogenesis. Adv Enzyme Regul 43 121-134. 

Thomas S, Fell DA. The role of multiple enzyme activation in metabolic flux control. Advan Enzyme Regul 1998 38 65-85. 

Maeda H (2001) The enhanced permeability and retention (EPR) effect in tumor vasculature the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul 41 189-207... 

Calder, P.C., N-3 polyunsaturated fatty acids and immune cell function,Adv Enzyme Regul, 37, 197, 1997. 

Localization, substrate specificity, and drug resistance conferred by conjugate export pumps of the MRP family. Advances in Enzyme Regulation, 40, 339-349. 

Phosphorylase was studied in depth. The enzyme from muscle was different from that catalyzing the same reaction in liver. Muscle phosphorylase but not that from liver, was activated by AMP, an early example of enzyme regulation by a ligand which was not a substrate. [Allosteric regulation was not postulated until the work of Jacob and... 

Such metal-nitrosyl complexes have great physiological significance and are involved for example in enzyme regulation and protection against oxidation [62],... 

The physiological roles of the yeast (and their human homologues) alkaline ceramidases are yet to be established. Since these enzymes regulate a series of bioactive lipids such as ceramide, sphingosine, and sphingosine-1-P, we predict that they have an important role in cell regulatory events. 

B. C. Goodwin, Oscillatory behavior in enzymatic control processes. Adv. Enzyme Regul. 3, 425-A38 (1965). 

Citrate synthase, isocitrate dehydrogenase and oxogluta-rate dehydrogenase are key enzymes regulating the flux through the cycle all three catalyse non-equilibrium reactions (Chapter 3). 

---