6 Key excerpts on "Enzyme Catalyzed Reaction"

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  eBook - ePub

  Medical Biochemistry

  • Antonio Blanco, Gustavo Blanco(Authors)
  • 2017(Publication Date)
  • Academic Press

    (Publisher)

  Countless chemical reactions take place at a given time in every living being. Many of them transform exogenous substances, which come with the diet, to obtain energy and the basic materials that will be used for the synthesis of endogenous molecules.

  Biochemical transformations are performed at a remarkable fast rate and with great efficiency. To reproduce them in the laboratory, these reactions would need extreme changes in temperature, pH, or pressure to take place; these changes are not compatible with cell survival. Under normal physiological conditions (37°C for warm-blooded organisms, pH near neutrality, and constant pressure), most of the reactions would proceed very slowly or may not occur at all. It is the presence of catalysts that allow chemical reactions in living beings to occur with great speed and under the mild conditions that are compatible with life.

  Enzymes are biological catalysts

  A catalyst is an agent capable of accelerating a chemical reaction without being part of the final products or being consumed in the process. In biological media, macromolecules called enzymes act as catalysts.

  As any catalyst, enzymes work by lowering the reaction activation energy (A e ) (see p. 152). Enzymes are more effective than most inorganic catalysts; moreover, enzymes show a greater specificity of effect. Usually inorganic catalysts function by accelerating a variety of chemical reactions, whereas enzymes catalyze only a specific chemical reaction. Some enzymes act on different substances, but generally, these are compounds with similar structural characteristics and the catalyzed reaction is always of the same type.

  The substances that are modified by enzymes are called substrates .

  The specificity of enzymes allows them to have high selectivity to distinguish among different substances and even between optical isomers of a compound. For example, glucokinase, an enzyme that catalyzes d -glucose phosphorylation, does not act on l

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  Essentials of Chemical Biology

  Structure and Dynamics of Biological Macromolecules

  • Andrew D. Miller, Julian A. Tanner(Authors)
  • 2013(Publication Date)
  • Wiley

    (Publisher)

  8

  Kinetics and catalysis

  8.1 Catalysis in chemical biology

  According to some theories about the origins of life, the key to the creation of organisms is molecular complexity that is sufficient to give self-organisation (see Chapter 10). However, self-organisation alone is insufficient to give life. Instead, self-organisation needs to be partnered with the capacity to accelerate or catalyse chemical inter-conversions as well. This capacity to catalyse chemical inter-conversions is known as catalysis. Catalysis is frequently performed by a catalyst, which is usually defined as an entity that enhances the rate of a given chemical reaction in both forward and reverse directions without being itself permanently changed in the process. Therefore, a biocatalyst is a biologically relevant catalyst. Typically, biocatalysts accelerate biological chemical reactions with relative rate enhancements of between 105 and 1010 relative to the non-catalysed reactions. Catalysis is universal to all cells of all organisms and the range and diversity of known biocatalysts is simply staggering! Biocatalysts are clearly an absolute fundamental for both the origin of life and the promulgation of life.

  Biocatalysts are overwhelmingly proteins (enzymes) and sometimes RNA nucleic acids (ribozymes). They catalyse an amazing diversity of reactions for myriads of different important reasons. Enzymes take centre stage in metabolism, which is the process by which chemical potential is generated and stored by coupling the synthesis of adenosine 5′-triphosphate (ATP) (the preferred ‘form’ of stored chemical energy in all cells) with the stepwise degradation and/or reorganisation of covalent bonds of primary metabolites such as glucose (Chapter 1). For instance, triose phosphate isomerase (TIM) (see Chapter 1) catalyses the seemingly innocuous interconversion between dihydroxyacetone phosphate and glyceraldehyde-3-phosphate in the catabolic pathway known as glycolysis (Figure 8.1 ). Yet surprisingly, TIM is now considered to be a ‘perfect enzyme’ (see Section 8.4.8), which makes the interconversion possible at a rate that is literally as fast as substrate reaches the enzyme active site. Indeed, without TIM the glycolysis pathway would be unable to deliver on a net gain of two ATP molecules for each glucose molecule consumed (see Figure 8.1 ). In a similar vein, the dimeric enzyme malate dehydrogenase (MDH) catalyses the mere reduction of a carbonyl functional group in oxalic acid to give malic acid, making use of the cofactor nicotinamide adenine dinucleotide hydride, reduced form (NADH) (Figure 8.2 ), yet this interconversion establishes closure of the tricarboxylic acid (TCA) cycle, which takes metabolites from glycolysis and delivers on a net gain of reducing cofactor molecules for each complete rotation through the TCA cycle. There are other types of catabolic enzyme, such as chymotrypsin, which within the gut digests polypeptides into oligopeptides (Figure 8.3 ), for absorption across the gut wall into the blood stream. Alternatively, ribonuclease A (RNAse A) does for RNA polynucleotide what chymotrypsin does for polypeptides, albeit by a very different mechanism (Figure 8.4 ). Enzymes are not only involved in catabolism (i.e. breaking down), but also play a role in anabolism (i.e. building up) of monomeric building blocks required for biological macromolecular assembly. In this respect, examples include alanine α-racemase (AlaR), glutamate α-decarboxylase and aspartate transaminase (aspAT) enzymes, which all make use of the cofactor pyridoxal phosphate (PLP) (Figure 8.5

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  eBook - ePub

  Biotechnology for Beginners

  • Reinhard Renneberg, Vanya Loroch(Authors)
  • 2016(Publication Date)
  • Academic Press

    (Publisher)

  biological catalysts —turning substances into other products without undergoing any change themselves.

  Due to enzymes, chemical reactions reach their equilibrium much faster and may be speeded up by a factor of up to 10 12 . It is the activity of enzymes that makes life possible at all. Turning sugar into alcohol and carbon dioxide is a matter of seconds for the enzymes in yeast cells, but without them it would take hundreds of years and be virtually impossible. Enzymes are highly effective, high-performing biocatalysts .

  In cells ranging in size between a tenth and a thousandth of a millimeter, thousands of coordinated enzymatic reactions take place every second (See Figs. 4.5 and 4.6 in Chapter 4 ).

  This can only work because each of the molecular catalysts involved recognizes its specific substrate among thousands of other compounds within a cell and turns it to a specific product. This process, called biocatalysis, takes place in the active site of the enzyme.

  Nearly all biological catalysts are proteins. However, RNA (ribonucleic acid) can also act as a biocatalyst (see Chapter: The Wonders of Gene Technology ). These ribozymes often break down other RNA molecules. RNA can also be used to build artificial aptamers that bind to designated compounds (see Chapter: Analytical Biotechnology and the Human Genome ).

  As early as 1894, the German chemist Emil Fischer (1852–1919), who was later awarded the Nobel Prize (Fig. 2.4 ), postulated that enzymes recognize their substrates on a lock-and-key principle . If the active site of an enzyme lies in a dimple (cavity, crevice) on the molecule’s surface, the substrate molecule must fit accurately, just like a key into its lock. Even slightly modified molecules will no longer interact with the enzyme. Lock-and-key is a viable preliminary explanation for the high substrate specificity of enzymes. It also explains why the shape of competing enzyme inhibitors (e.g., penicillin) strongly resembles that of the original substrate. Like a skeleton key, they block the active site of an enzyme (competitive inhibition

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  Environmental Microbiology for Engineers

  • Volodymyr Ivanov(Author)
  • 2020(Publication Date)
  • CRC Press

    (Publisher)

  The enzyme is regenerated in this reaction and starts up a new reaction cycle. The coenzyme, C, is an active catalytic center of the enzyme molecule, but it is often weakly bound with the enzyme.

  Major Features of Enzymes

  The major features of all enzymes are as follows:

  1. 1. Enzymes are protein catalysts.
  2. 2. An enzyme possesses high specificity, i.e. it increases the rate of one biochemical reaction.

  So, if cell metabolism is performed by the network of 10,000 biochemical reactions, the cell produces 10,000 different enzymes.

  Mechanism of Enzymatic Catalysis

  The constant k of the chemical reaction rate depends on the energy of activation, which is defined by the Arrhenius equation:

  ln k = ( − E a / R ) × ( 1 / T ) + ln A ,

  where

  Ea is the activation energy of chemical reaction,

  R is the gas constant (8,31 J/K mol), T is the absolute temperature (K), and A is the frequency factor for reaction.

  The activation energy is the minimum amount of energy required to initiate a chemical reaction. An enzyme significantly decreases the energy of activation of a reaction due by stereochemical arrangement of a substrate inside the 3D structure of a protein, which is favorable for the initiation of the reaction. A decrease in activation energy increases the rate of the reaction (Figure 2.9 ). Typically, enzyme-catalyzed biochemical reactions are a thousand or even a million times faster than the same chemical reaction without an enzyme.

  Specificity of Enzymes

  One biochemical reaction requires one specific enzyme. The specificity of an enzyme is created by the stereochemical specificity of the binding between the active center of enzyme and substrate. Bacterial cells require several thousand biochemical reactions to reproduce. Respectively, several thousand specific enzymes must be synthesized in the cell to catalyze these biochemical reactions.

  Active Center and Coenzyme

  The active center or site of an enzyme is a small part of the enzyme molecule where the substrate is bound by temporal chemical bonds and then transformed to product. Very often, catalysis is performed not by sequence of amino acids in an enzyme molecule but by the small molecule that is attached, sometimes reversibly, to the enzyme molecule. This catalytic unit is called a coenzyme or cofactor. It could be an inorganic or organic non-protein compound.

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  Biochemistry

  • Raymond S. Ochs(Author)
  • 2021(Publication Date)
  • CRC Press

    (Publisher)

  S enforces specificity for the catalyzed reaction.

  FIGURE 6.2 Energy of activation in uncatalyzed and catalyzed reactions. On the left is the high energy intermediate of an uncatalyzed reaction between substrate and product. On the right, an enzyme-catalyzed reaction shows an additional high-energy but stable region, the intermediate enzyme–substrate complex (ES). The enzymatic reaction course has higher reaction barriers on either side; the highest barrier that defines the Eact is lower than that of the uncatalyzed reaction.

  The chemical transformations of the substrate on the enzyme surface proceed as they would in nonenzymatic processes (e.g., oxidation, proton transfer, or electron rearrangement). Enzymatic reactions are orchestrated with precision. The orientation of the substrate with ancillary groups – or even other substrates – benefits from selective binding to a specific region of the enzyme called the active site. The intermediates symbolized here (i.e., ES) will later be fleshed out in chemical terms. For now, our focus is on how the reaction rate changes as the concentration of the substrate is varied.

  Box 6.1 Activation Energy and Murphy’s Law

  The concept of activation energy can be made intuitive by dispelling a common myth known as “Murphy’s Law” which states that “if anything can go wrong, it will”. While declaring this law generates a cynical acquiescence in listeners, it is in fact wrong – one of the philosophical insights of chemistry. A more accurate law is: “most things can go wrong, but don’t”.

  The more stable state of a building is a pile of bricks rather than the very orderly arrangement of the structure, yet we hardly fear an imminent collapse while we are inside. This is because it would take a wrecking ball – a large investment of extra energy – to reduce the building to a more stable arrangement. Similarly, virtually all reactions that can proceed to a more stable form nonetheless require an input of great energy to get them going. In the molecular world, we need to think of this as providing increased movement of molecules (rotations, vibrations, translations) before the reaction can occur. Thus, even though the final state may be more stable than the initial state, activation energy is always required. Murphy was apparently an incautious investigator who rushed to publication.

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  Biotransformations and Bioprocesses

  • Mukesh Doble, Anil Kumar Kruthiventi, Vilas Ganjanan Gaikar, Mukesh Doble, Anil Kumar Kruthiventi, Vilas Ganjanan Gaikar(Authors)
  • 2004(Publication Date)
  • CRC Press

    (Publisher)

  B independently, by keeping the initial concentration of the other substrate constant.

  FIGURE 7.1 Effect of initial concentration on initial rate as a function of reaction order.

  A reaction of the form A¨P¨Q is called a series reaction, where P is the intermediate, whereas a reaction of the form A¨P and A¨Q is known as a parallel reaction.

  Cell growth process is an autocatalytic reaction, where the reaction exhibits an induction period with very low rate at initial time, followed by a sudden increase in rate

  until all the substrate is consumed. The rate curve exhibits a sigmoidal-shaped curve with an induction period. Autocatalytic behavior is exhibited during the exponential growth phase of the biocell, and it is described in more detail later.

  7.2 ENZYME-CATALYZED REACTION

  Enzyme behaves like any other catalyst, by forming enzyme-substrate complex, but this is not similar to the transition state, which organic molecules pass through. The formation of enzyme-substrate complex is based on two mechanisms, lock and key and hand and glove. In the lock-and-key mechanism it is assumed that the fit happens because the size and shape of the active site in the enzyme matches exactly with that of the substrate, analogous to a lock and key. In the hand-and-glove mechanism the enzyme active site adjusts itself both in size and/or shape to suit that of the substrate. Factors like pH, temperature, chemical agents (such as alcohol and urea), irradiation, mechanical shear stress, and hydrostatic pressure alter the active site and affect the performance of enzymes.

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