Enzymes in Metabolism

Organisms also require very low levels of a number of micronutrients, which are usually used by essential enzymes that enable metabolic reactions to occur. For plants, essential micronutrients include the elements boron, chlorine, copper, iron, manganese, sodium, vanadium, and zinc. The bacteria that fix atmospheric nitrogen required by plants use trace levels of molybdenum. Animals require in their diet elemental micronutrients including iron and selenium as well as miaonutrient vitamins consisting of small organic molecules. 

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Saier, M., Jr., 1987. Enzymes in Metabolic Pathways. New York Harper and Row. 

Allosteric enzymes show various activation and inhibition effects which are competitive in nature and related to conformational changes in the structure of the enzyme. Such allosteric enzymes are often crucial enzymes in metabolic pathways and exert control over the whole sequence of reactions. The name allostery refers to the fact that inhibition of the enzyme is by substances that are not similar in shape to the substrate. 

Buhler, D.R. and Williams, D.E. 1989, Enzymes involved in metabolism of PAHs by fishes and other aquatic animals Oxidative enzymes (or Phase I enzymes). In Metabolism of Polycyclic Aromatic Hydrocarbons in the Aquatic Environment. Varanasi, U., Ed. CRC Press Boca Raton, El pp. 151-184. 

Knowledge of the value also provides information abont the role of enzymes in metabolic pathways. Two examples are given. 

EQUILIBRIUM DIALYSIS EQUILIBRIUM ENZYMES IN METABOLIC PATHWAYS... 

M2. Mason, M., Effects of conjugated steroids on enzymes. In Metabolic Conjugation and Metabolic Hydrolysis (W. H. Fishman, ed.), Vol. 1, pp. 121-156. Academic Press, New York, 1970. 

Feedback can also be positive. Since AMP is a product of the hydrolysis of ATP, its accumulation is a signal to activate key enzymes in metabolic pathways that generate ATP. For example, AMP causes allosteric activation of glycogen phosphorylase, which catalyzes the first step in the catabolism of glycogen. As is shown in Fig. 11-5, the allosteric site for AMP or IMP binding is more than 3 nm away from the active site. Only a... 

It is obvious that the answer is the principle of spatial correlation, that is, the compartmentalization of a metabolism via the formation of oligomeric enzymes, enzyme clusters, and physical association of enzymes in metabolic sequences anchored on membranes. 

Benzoylformate decarboxylase (BFD), a TPP-dependent enzyme, features a high degree of sequence similarity with a whole family of other TPP-dependent decarboxylases, among them pyruvate decarboxylase (PDC), one of the most important enzymes in metabolism. 

At the present rate of experimental activity in this field, there is no doubt that the importance of these latter enzymes in metabolic processes will be established within the next few years. At present, though, these enzymes are of limited value to structure proof studies on phospholipids. If a more rigorous description of the characteristics of these enzymes is required, reference... 

To incorporate an even wider variety of biologic data for predicting missing enzymes in metabolic enzyme networks, kernel methods are used. A kernel is a mathematic function that can take as input a variety of data for a specific set of entities and transform it such that the input entities can be classified as distinctly as possible. This method consists of two steps a training phase and a test phase. The training phase consists of using data for which the properties are known in advance. Then, the test phase can be used to assess the applicability of the properties to new input data sets. 

TABLE 11.2 Participation of the CYP Enzymes in Metabolism of Some Clinically Important Drugs ... 

Allosteric enzymes in metabolic pathways change their activity in response to molecules that either stimulate or inhibit their catalytic activity. While the end product of an eri2yme cascade is used up, the cascade continues to synthesize that product. The result is a steady-state condition in which the product is used up as it is produced and there is no significant accumulation of product. However, when the product accumulates above the steady-state level for any reason, that is, in excess of the cell s needs, the end product acts as an inhibitor of the first enzyme of the sequence. This is called allosteric inhibition, and is a type of feedback inhibition. 

At the moment no decision can be made as to whether or not erythrocuprein is an essential enzyme in metabolism. In order to assign a specific role to it, two criteria must be fulfilled firstly appropriate ligands bound to the Cu2+ must be able to induce a superoxide dismutase ... 

Another important class of carbon compounds, the cyanides, contain the anion group C=N . Cyanide ions are extremely toxic because they bind almost irreversibly to the Fe(III) ion in cytochrome oxidase, a key enzyme in metabolic processes. Hydrogen cyanide, which has the aroma of bitter almonds, is even more dangerous because of its volatility (b.p. 26°C). A few tenths of 1 percent by volume of HCN in air can cause death within minutes. Hydrogen cyanide can be prepared by treating sodium cyanide or potassium cyanide with acid ... 

Pantothenate kinase phosphorylates Vitamin B6, the first and rate controlling step in Coenzyme A biosynthesis. Due to the lack of pantothenate kinase inhibitors and activators, the exact physiological role of this enzyme in metabolism and disease is not yet known. In a recent study aimed at the discovery of antimicrobial agents, a set of novel inhibitors of S. aureus pantothenate kinase were disclosed that also inhibited mammalian (murine) pantothenate kinase with high micromolar IC50 values.235 A team at St. Jude Children s Hospital studied a library of known bioactive compounds to find inhibitors of pantothenate kinase. Several inhibitors with IC50 values below 10 pM were identified.236... 

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