Regulating biochemical reactions

The role of enzymes in regulating biochemical reactions makes them an important target in medicinal chemistry and drug research. If a biochemical pathway runs out of control, it may sometimes be regulated by changing the turnover rate of an enzyme-catalyzed step in the pathway through (partial) inhibition of the enzyme. Once the kinetical, chemical, and structural details of an enzyme mechanism are understood, efficient inhibitors can be designed. However, quite different mechanisms of inhibition are possible. 

An intricate system of interrelated control mechanisms regulate biochemical reaction sequences. Metabolic pathways are controlled not only by specific activity and inherent kinetic properties of enzymes in the pathway but also by the intracellular concentration of certain essential substrates, activators or inhibitors. PP-ri-bose-P is an essential substrate of purine, pyrimidine and pyridine biosynthesis. The intracellular concentration of PP-ribose-P represents a balance between its synthesis by PP-ribose-P synthetase and its utilization which is catalyzed by several different phosphori-bosyltransferase (PRT) enzymes as well as non-specific phosphatases. Alterations in the rate of synthesis or degradation of PP-ribose-P, whether drug induced or secondary to an inborn error, could potentially change the intracellular concentration of this compound. 

One of the most important goals of research in medicinal chemistry is to discover new small molecules that bind to a protein or to other biopolymeric structures of pharmacological interest. In particular, enzymes that regulate biochemical reactions are important targets in contemporary medicinal chemistry. Compounds binding specifically to one of these targets can be useful in the treatment of various diseases. 

Control of relative humidity is needed to maintain the strength, pHabiUty, and moisture regain of hygroscopic materials such as textiles and paper. Humidity control may also be required in some appHcations to reduce the effect of static electricity. Temperature and/or relative humidity may also have to be controlled in order to regulate the rate of chemical or biochemical reactions, such as the drying of varnishes, the appHcation of sugar coatings, the preparation of synthetic fibers and other chemical compounds, or the fermentation of yeast. 

Copper is an essential micronutrient required in the growth of both plants and animals. In humans, it helps in the production of blood haemoglobin. In plants, copper is an important component of proteins found in the enzymes that regulate the rate of many biochemical reactions in plants. Plants would not grow without the presence of these specific enzymes. Research projects show that copper promotes seed production and formation, plays an essential role in chlorophyll formation and is essential for proper enzyme activity, disease resistance and regulation of water in plants (Rehm and Schmitt, 2002). 

The subject of biochemical reactions is very broad, covering both cellular and enzymatic processes. While there are some similarities between enzyme kinetics and the kinetics of cell growth, cell-growth kinetics tend to be much more complex, and are subject to regulation by a wide variety of external agents. The enzymatic production of a species via enzymes in cells is inherently a complex, coupled process, affected by the activity of the enzyme, the quantity of the enzyme, and the quantity and viability of the available cells. In this chapter, we focus solely on the kinetics of enzyme reactions, without considering the source of the enzyme or other cellular processes. For our purpose, we consider the enzyme to be readily available in a relatively pure form, off the shelf, as many enzymes are. 

One of the most distinguishing features of metabolic networks is that the flux through a biochemical reaction is controlled and regulated by a number of effectors other than its substrates and products. For example, as already discovered in the mid-1950s, the first enzyme in the pathway of isoleucine biosynthesis (threonine dehydratase) in E. coli is strongly inhibited by its end product, despite isoleucine having little structural resemblance to the substrate or product of the reaction [140,166,167]. Since then, a vast number of related... 

Fig. 3.2. The individual steps of intercellular communication. Upon reception of a triggering stimulus, the signal is transformed into a chemical messenger within the signaling cell. The messenger is secreted and transported to the target cell, where the signal is registered, transmitted further, and finally converted into a biochemical reaction. Not shown are processes of termination or regulation of communication which can act at any of the above steps.

The highly variable nature of signaling pathways is also expressed by the fact that different receptors and signaling pathways can induce the same biochemical reaction in a cell. This is exemplified by the release of Ca, which can be regulated via different signaling pathways (see chapters 5-7). 

A biochemical system is at the center of the cell cycle, of which the most important players are Ser/Thr-specific protein kinases and regulatory proteins associated with these. The activity of this central cell cycle apparatus regulates processes downstream that help to carry out the many phase-specific biochemical reactions of the cell cycle in a defined order. 

It is highly unlikely that xenon participates in biochemical reactions although it has been shown to have an inhibitory action at NMDA receptors. It has also been reported by Petzelt in 1999 to inhibit Ca2+ regulated transitions in the cell cycle of human endothelial cells. Elimination of xenon is almost entirely through the lungs. Unlike nitrous oxide, xenon does not appear to have any adverse effects on the bone marrow, and there is no evidence of teratogenicity or fetotoxicity. 

Many Biochemical Reactions Require Energy Biochemical Reactions Are Localized in the Cell Biochemical Reactions Are Organized into Pathways Biochemical Reactions Are Regulated Organisms Are Biochemically Dependent on One Another... 

Biochemical reactions are regulated according to need by controlling the amount and activity of enzymes in the system. 

Enzymes are globular proteins whose sole function is to catalyze biochemical reactions. The most important properties of all enzymes are their catalytic power, specificity, and capacity to regulation. The characteristics of enzymes (Copeland, 2000 Fersht, 1985 Kuby, 1991 Price and Stevens, 2000) can be summarized as follows ... 

The individual reactions affected by iron stress can be considered as regulated biochemical pathways, although regulation by iron is not understood. The mechanism of iron absorption and transport involves the release of hydrogen ions by the root, which lowers the pH of the root zone. This favors Fe3+ solubility and reduction of Fe3 to Fe2+. Reductants are released by roots or accumulate in roots of plants that are under iron stress. These "reductants, along with Fe3+ reduction by the root, reduce Fe3+ to Fe2+, and Fe2+ can enter the root. Ferrous iron has been detected throughout the protoxylem of the young lateral roots. The Fe2+ is probably kept reduced by the reductant in the root, and it may or may not have entered the root by a carrier mechanism. The root-absorbed Fe2+ is believed to be oxidized to Fe3, chelated by citrate, and transported in the metaxylem to the tops of the plant for use. We assume Fe2+ is oxidized as it enters the metaxylem because there is no measureable Fe2+ there (13), and Fe3+ citrate is transported in the xylem exudate (30, 31,32). 

As mentioned earlier, understanding the pH equation and the regulation and control of pH is fundamentally important when considering very many life and health processes. A simple indication of the importance of environmental pH is for growth of crops (soil pH) and acid rain (water pH), which can affect the ecosystem. Indeed, optimum conditions for purification of water and sewage treatment also are pH dependent. Physiologically, pH is critical to maintain normal body functions and key to biochemical reactions in the blood and other body fluids. Buffers and buffer systems are the primary means to regulate and maintain pH, and are discussed in more detail below (with examples in Appendix 3). 

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