Enzymes control

In a biocatalytic biosensor the molecular recognition component is an enzyme. Enzymes, macromolecular catalysts that are manufactured by plants and animals, affect the rates of biochemical reactions. Virtually all of the millions of chemical reactions involved in Hfe processes have associated enzymes controlling the rates. CoUectively, there are several thousand enzymes known and perhaps many thousand more yet to be discovered. 

PEP carboxylase occurs in yeast, bacteria, and higher plants, but not in animals. The enzyme is specifically inhibited by aspartate, which is produced by transamination of oxaloacetate. Thus, organisms utilizing this enzyme control aspartate production by regulation of PEP carboxylase. Malic enzyme is found in the cytosol or mitochondria of many animal and plant ceils and is an NADPIT-dependent enzyme. 

Enzyme-controlled transformations of fluorinated heterocycles 97MI32. 

The search for inhibitors of this pathway began with the first key regulatory enzyme, HMG CoA reductase. Several clinically useful inhibitors of HMG CoA reductase are now known. One of the most successful, Mevacor, produced by Merck, is one of the pharmaceutical industry s best selling products. However, the problem with inhibiting a branched biosynthetic pathway at an early point is that the biosynthesis of other crucial biomolecules may also be inhibited. Indeed, there is some evidence that levels of ubiquinone and the dolichols are affected by some HMG CoA reductase inhibitors. Consequently, efforts have recently been directed towards finding inhibitors of squalene synthase, the enzyme controlling the first step on the route to cholesterol after the FPP branch point. 

Topoisomerase enzymes control and modify the topologic states of DNA. The mechanisms of these enzymes involve DNA cleavage and strand passage through the break, followed by religation of the cleaved DNA. Two main forms of topoisomerase exist. The type... 

One form of biological poisoning mirrors the effect of lead on a catalytic converter. The activity of an enzyme is destroyed if an alien substrate attaches too strongly to the enzyme s active site, because then the site is blocked and made unavailable to the true substrate (Fig. 13.42). As a result, the chain of biochemical reactions in the cell stops, and the cell dies. The action of nerve gases is believed to stem from their ability to block the enzyme-controlled reactions that allow impulses to travel through nerves. Arsenic, that favorite of fictional poisoners, acts in a similar way. After ingestion as As(V) in the form of arsenate ions (As043 ), it is reduced to As(III), which binds to enzymes and inhibits their action. 

Figure 10.1. Schematic diagram showing inhibition of synthesis of amino acids a) single chain inhibition occurs when enzyme controlling committed step (S ) is inhibited by increasing concentrations of product AAj b) branched chain inhibition of by increased concentration of AA2 occurs at a post-branching step (sj), while permitting continued production of product of other branch (AAj). In general, each step is controlled by a single enzyme.

The principal enzymes controlling glycogen metabolism—glycogen phosphorylase and glycogen synthase— are regulated by allosteric mechanisms and covalent modifications due to reversible phosphorylation and... 

There are three distinct nuclear DNA-dependent RNA polymerases in mammals RNA polymerases I, II, and III. These enzymes control the transcriptional function—the transcription of rRNA, mRNA, and small RNA (tRNA/5S rRNA, snRNA) genes, respectively. 

A series of hypocholesteremic agents were isolated from Monascus and named monacolin J, K, and L. These polyketides were first isolated from cultures of Penicillium citrinum and they can inhibit specifically the enzyme controlling the rate of cholesterol biosynthesis. They are currently used in China in traditional and modem medicine. 

Mutch E, Blain PG, Williams FM. 1992. Interindividual variations in enzymes controlling organophosphate toxicity in man. Hum Exp Toxicol 11 109-116. 

After measuring the fluxes through the metabolic network, it is necessary to determine the extent to which each pathway or enzyme controls the net fluxes. Metabolic control analysis (MCA) is a technique used to elucidate how flux control is distributed in a metabolic network, thereby providing the information for identification of potential targets for metabolic engineering [8],... 

The problems in the nucleoside synthesis arise in the linkage of the 3-N atoms of the pyrimidines and the 9-N atoms of the purines with the l -C atom of ribose, not only without enzyme control, but also under conditions extant on the primordial Earth. How might such reactions occur There have naturally been many attempts... 

Bugg, T. D. H., and Lin, G., Solving the Riddle of the Intradiol and Extradiol Catechol Dioxygenases How Do Enzymes Control Hydroperoxide Rearrangements. J. Chem.Soc. Chem. Commun., 2001. pp. 941-952. 

Specific enzymes control histamine synthesis and breakdown 253 Several forms of histidine decarboxylase may derive from a single gene 254... 

Specific enzymes control histamine synthesis and breakdown. Figure 14-3 summarizes the major mechanisms for the synthesis and metabolism of histamine. 

Allosteric regulators bind to the target enzyme in a non-covalent manner. An entirely different enzyme control mechanism is covalent modification. Here, the conformation of the enzyme protein, and thereby its activity, is changed by the... 

Enzymes control the rate of nearly every reaction in your body. They are... 

Fat facets Deubiquitinating enzyme controlling synapse development in Drosophila... 

Similarly, specific catalysts called enzymes are important factors in determining what reactions occur at an appreciable rate in biological systems. For example, adenosine triphosphate is thermodynamically unstable in aqueous solution with respect to hydrolysis to adenosine diphosphate and inorganic phosphate. Yet this reaction proceeds very slowly in the absence of the specific enzyme adenosine triphosphatase. This combination of thermodynamic control of direction and enzyme control of rate makes possible the finely balanced system that is a hving cell. 

Hunter T, Cooper JA, In Enzyme Control by Protein Phosphorylation. (Eds Boyer PD, Krebs EG), p. 191. Academic Press, New York, 1986. 

Assay of Enzymatic Hydrolysis of Synthetic Solid Polymers. Hydrolysis of solid polymers was measured by the rate of their solubilization, and the measurement process does not necessarily involve complete hydrolysis into the constituent parts. The rate was determined by measuring the water-soluble total organic carbon (TOC) concentration at 30 °C in the reaction mixture using a Beckman TOC analyzer (Model 915-B). In the substrate and enzyme controls, enzyme or substrate was omitted from the reaction mixture. 

The particle size of each polyester powder was ranked A, B, C, D, or E, corresponding respectively to roughly less than 0.25 mm, less than 0.50 mm, less than 1.0 mm, 0.25-1.5 mm, 0.25-3 mm. Each reaction mixture contained ioo p mol of phosphate buffer (pH T.O), 1 mg of surfactant Plysurf A210G, 300 mg of the polyester powder and 60 y g of R. arrhizus lipase (or 300 pg of R. delemar lipase) in a total volume of 10.0 ml. In the case of R. delemar lipase, surfactant was omitted and pH of phosphate buffer was 6.0. In the substrate and enzyme controls, enzyme or substrate was omitted from the reaction mixture. 

Since a knowledge of the correct tautomeric form of the pyrimidines is a requisite for understanding the mode of binding to active sites, as well as nucleic acid structure and modification, the formulae of the conventionally-named 2- and 4-hydroxypyrimidines are presented in the correct lactam, or pyrimidone, form in this chapter. Other physical properties of the pyrimidines, such as dissociation constants, protonation sites, and distribution coefficients, are presented in cases where there is a known relation to drug activity. Biogenesis and enzyme control mechanisms are discussed where they relate to an understanding of inhibitor action. 

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