Protein-catalyzed reactions

Enzymes catalyze an enormous variety of biochemical reactions. They serve to regulate the rate of these specific reactions, for which they have been uniquely designed. Like any other catalyst, they alter only the rate of a reaction their chemical structure is not altered by the reaction. They do not alter the equilibrium between the reactants and products but merely increase the rate at which that equilibrium is attained. Enzymes may, however, participate in the reaction, transiently changing the chemical structure, but are quickly regenerated to their original form. In order to understand how an enzyme works, it is necessary to know its three-dimensional structure and, more importantly, the structure of the enzyme complex involving substrates, intermediates and products of the reaction. 

Enzymes bind their substrates with a high degree of specificity. The reactions that a particular enzyme catalyzes are also specific and take place at a particular location in the enzyme, its active site. This active site is made up of amino acid side chains arranged in such a way that 

The first crystal structure of an enzyme, that of lysozyme, was determined by David C. Phillips and coworkers in 1965. The most striking feature in the three-dimensional structure of lysozyme is a prominent cleft that traverses one face of the molecule. The X-ray structure of lysozyme complexed with a three-residue oligosaccharide showed that this cleft was, indeed, the substrate-binding site. The crystal structure of this complex provided the first three-dimensional model for how enyzmes work. 

A serine protease has four major requirements. The catalytic triad Asp, His, and Ser, are essential for the chemical mechanism. The oxyan-ion hole contains side chains that form hydrogen bonds to the oxygen atom that has developed a negative charge. The specificity pocket pro- 

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Both in linear and nonlinear methods, the minimum time delay accessible to the experimenter is the time resolution, and it is determined by either the duration of the pump or the probe pulse, whichever is longer. Two linear methods are discussed in section II, while a nonlinear method is presented in section IV. Typical timescales for protein catalyzed reactions range in the nanosecond (ns) to millisecond (ms) time range and the time resolution must be much better in order to sample the time range sufficiently. However, there are processes in proteins that are much faster, often occurring at femtosecond (fs) timescales (Franzen et al. 1995 Lim et al. 1993 Jackson et al. 1994 Armstrong et al. 2003 Nagy et al. 2005). To observe these processes. 

Table I also shows the great diversity of organisms in which iron—sulfur proteins have been detected. Thus far there is no organism which when appropriately examined has not contained an iron-sulfur protein, either in the soluble or membrane-bound form. Iron-sulfur proteins catalyze reactions of physiological importance in obligate anaerobic bacteria, such as hydrogen uptake and evolution, ATP formation, pyruvate metabolism, nitrogen fixation, and photosynthetic electron transport. These properties and reactions can be considered primitive and thus make iron-sulfur proteins a good place to start the study of evolution. These key reactions are also important in higher organisms. Other reactions catalyzed by iron-sulfur proteins can be added such as hydroxylation, nitrate and nitrite reduction, sulfite reduction, NADH oxidation, xanthine oxidation, and many other reactions (Table II).

The activities of proteins are also regulated by the concentrations of a variety of other molecules which they bind noncovalently. The velocity of processes catalyzed by enzymes increases with substrate concentration until concentrations at which binding sites are saturated are reached. Conversely, competitive inhibitors that bind at the active site and block substrate binding reduce rates of protein catalyzed reactions, with the magnitude of the inhibition increasing with the concentration of competitive inhibitor. The ability of the products of many enzyme catalyzed reactions to bind at the active site provides a simple means of feedback regulation. When substrate concentrations are low and product concentrations are high, enzymatic activity will be diminished. Conversely, when substrate concen-... 

As far as HDL levels and metabolism are concerned, one result of the LCAT- and transfer protein-catalyzed reactions is the production of a dynamic spectrum of particles with a wide range of sizes and lipid compositions (Chapter 19). Nascent HDL particles contain mostly apo A1 and phospholipids, and undergo modulation and maturation in the circulation. For instance, the unesterified cholesterol incorporated into plasma HDL is converted to cholesteryl esters by LCAT, creating a concentration gradient of cholesterol between HDL and cell membranes, which is required for efficient cholesterol efflux from cells to HDL. In addition, cholesteryl ester transfer protein transfers a significant amount of HDL cholesteryl ester to VLDL, IDL, and LDL for further transport, primarily to the liver. Thus, a substantial fraction of cell-derived cholesterol is delivered as part of HDL indirectly to the liver via hepatic endocytic receptors for IDL and LDL this process is termed reverse cholesterol transport . However, receptor-mediated delivery of HDL cholesterol to cells is fundamentally different from the classic LDL receptor-mediated endocytic pathway, as described in Section 7.3.2. 

Proteins are macromolecules present in all living cells. About 50% of your body s dry mass is protein. Some proteins are structural components in animal tissues they are a key part of skin, nails, cartilage, and muscles. Other proteins catalyze reactions, transport oxygen, serve as hormones to regulate specific body processes, and perform other tasks. Whatever their function, all proteins are chemically similar, being composed of smaller molecules called amino acids. 

Table 3. Multienzyme complexes and multifunctional proteins catalyzing reactions of secondary metabolism...

Additives (say less than 10 ) mole fraction, which have sensitive effects on anti-crystalline properties of pure water at ambient temperatures, might also show sensitive interference with protein catalyzed reactions. Obvious examples are H2O2, H2S, NH3, (NH2)2, HCN, CH3NO, CH3OH, (CH20H)2 or glycerol. Inorganic trace control additives to examine are Li OH, CO2, N2O. 

The oxidative hypothesis states that FALS mutant SODl proteins catalyze reactions with hytfrogen peroxide or peroxynitrite that damage cellular con5>onents that are critical for motor neuron viability (P). For these chemistries to occur, copper must be bound in the active site of SODl to promote the oxidative reactions. 

Enzymes are basically specialty proteins (qv) and consist of amino acids, the exact sequence of which determines the enzyme stmcture and function. Although enzyme molecules are typically very large, most of the chemistry involving the enzyme takes place in a relatively small region known as the active site. In an enzyme-catalyzed reaction, binding occurs at the active site to one of the molecules involved. This molecule is called the substrate. Enzymes are... 

Like most chemical reactions, the rates of enzyme-catalyzed reactions generally increase with increasing temperature. However, at temperatures above 50° to 60°C, enzymes typically show a decline in activity (Figure 14.12). Two effects are operating here (a) the characteristic increase in reaction rate with temperature, and (b) thermal denaturation of protein structure at higher tem-... 

Amide hydrolysis is common in biological chemistry. Just as the hydrolysis of esters is the initial step in the digestion of dietary fats, the hydrolysis of amides is the initial step in the digestion of dietary proteins. The reaction is catalyzed by protease enzymes and occurs by a mechanism almost identical to that we just saw for fat hydrolysis. That is, an initial nucleophilic acyl substitution of an alcohol group in the enzyme on an amide linkage in the protein gives an acyl enzyme intermediate that then undergoes hydrolysis. 

Steps 1-2 of Figure 29.5 Acyl Transfers The starting material for fatty-acid synthesis is the thioesteT acetyl CoA, the ultimate product of carbohydrate breakdown, as we ll see in Section 29.6. The synthetic pathway begins with several priming reactions, which transport acetyl CoA and convert it into more reactive species. The first priming reaction is a nucleophilic acyl substitution reaction that converts acetyl CoA into acetyl ACP (acyl carrier protein). The reaction is catalyzed by ACP transacyla.se. 

Many reactions that take place slowly under ordinary conditions occur readily in living organisms in the presence of catalysts called enzymes. Enzymes are protein molecules of high molar mass. An example of an enzyme-catalyzed reaction is the decomposition of hydrogen peroxide ... 

The natural polymers known as proteins make up about 15% by mass of our bodies. They serve many functions. Fibrous proteins are the main components of hair, muscle, and skin. Other proteins found in body fluids transport oxygen, fats, and other substances needed for metabolism. Still others, such as insulin and vasopressin, are hormones. Enzymes, which catalyze reactions in the body, are chiefly protein. 

Multifunctional Proteins Catalyze the Early Reactions of Pyrimidine Biosynthesis... 

Enzymes are proteins catalyzing all in vivo biological reactions. Enzymatic catalysis can also be utilized for in vitro reactions of not only natural substrates but some unnatural ones. Typical characteristics of enzyme catalysis are high catalytic activity, large rate acceleration of reactions under mild reaction conditions, high selectivities of substrates and reaction modes, and no formation of byproducts, in comparison with those of chemical catalysts. In the field of organic synthetic chemistry, enzymes have been powerful catalysts for stereo- and regioselective reactions to produce useful intermediates and end-products such as medicines and liquid crystals. ... 

Theoretical studies that has investigated the homolysis step in different enzymatic systems [68-70] reveal that small models comprising only the corrin ring and two ligands are insufficient and that inclusion of more amino acids are essential to stabilize the radical intermediates. Recently, a QM/MM study of the initial phase of the glutamate mutase-catalyzed reaction found a large electrostatic stabilization by the surrounding protein [70], In our study of MCM we employed the ONIOM QM MM approach to reveal the role of the protein in the rupture of the Co—C5 bond [29],... 

Although also iron-sulfur proteins, the rubredoxins do not generate H2S on acidification since in this case the thiol groups are contributed by cysteinyl residues in the polypeptide chain. The function of clostridial rubredoxin is as yet unknown in Pseudomonas sp. a similar protein catalyzes the co-hydroxylation of alkanes, a reaction requiring molecular O2. 

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