Coenzyme

6 Key excerpts on "Coenzyme"

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  eBook - ePub

  Chemistry of Biomolecules, Second Edition

  • S. P. Bhutani(Author)
  • 2019(Publication Date)
  • CRC Press

    (Publisher)

  A Coenzyme cannot function alone but can be reused several times when paired with an enzyme. Coenzymes are heat stable, low molecular weight organic compounds required for the activity of enzymes. Coenzymes act as group transfer reagents. These are reusable non-protein molecules that contain carbon. They bind loosely to an enzyme at the active site to help catalyse reactions. They are linked to enzymes by non-covalent forces. Most Coenzymes are vitamins, vitamins derivatives or derived from nucleotides.

  C.  Cofactors

  Unlike Coenzymes true cofactors are reusable non-protein molecules that do not contain carbon i.e., they are inorganic cofactors. Usually they are metal ions such as iron, zinc, cobalt, copper, magnesium etc. that loosely bind to an enzyme’s active site to carry out the enzymatic reactions.

  Metal ions are Lewis acids i.e., electron pair acceptors. Therefore, they can act as Lewis acid base cataysts. We know that they can form coordination compounds by behaving as Lewis acids. These coordination compounds are an important part of metal ions in biological systems. These coordination compounds formed by metal ions tend to have specific geometries, which help in positioning the group involved in a reaction for optiomum catalysis.

  Without Coenzymes or cofactors enzymes cannot catalyse reactions effectively. In fact, the enzyme may not function at all. If reactions cannot occur at the normal catalysed rate, then an organism will have difficulty in sustaining life.

  D.  Functions of Coenzymes

  We have seen that when an enzyme gains a Coenzyme it becomes a holoenzyme or active enzyme. Active enzymes convert substrates into products an organism requires to carry out the essential functions whether chemical or physiological. Coenzymes like enzymes can be reused and recycled without changing reaction rate. When an enzyme is denatured by extreme temperature or pH, the Coenzyme can no longer attach to the active site.

  The Coenzymes perform two functions. One is to bind to the enzyme creating an active site so that the substrate can bind and the other is to provide some functional groups in order to help in the catalytic activity of the enzyme.

  For enzymatic reactions a Coenzyme binds to an apoenzyme to give holoenzyme or active enzyme. It is the holoenzyme that binds to the substrate to perform the reaction. That means the role of the Coenzyme is in the formation of a stable complex between the substrate and enzyme as shown in Fig. 3.6

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  eBook - ePub

  Principles of Enzymology for the Food Sciences

  • John R. Whitaker(Author)
  • 2018(Publication Date)
  • Routledge

    (Publisher)

  12Enzyme Cofactors

  I. General Nature of Cofactors

  Many enzymes, on hydrolysis, give only amino acids; therefore, their catalytic properties must reside in a unique arrangement of amino acid residues. Other enzymes contain, in addition to the polypeptide chain(s), small molecules that are essential for activity of the enzyme. These small molecules, referred to as cofactors, vary from the complexity of the B12 Coenzymes to the simplicity of inorganic ions. We shall discuss these cofactors under the general groupings of (a) Coenzymes, (b) prosthetic groups, and (c) inorganic ions.

  A. Distinguishing Features of Coenzymes and Prosthetic Groups

  In general, Coenzymes are attached less firmly to the protein portion of the enzyme than are prosthetic groups. However, there is considerable overlap between the two types of cofactors in the degree of binding to protein, so that classification based on this distinction alone frequently is equivocal. The best method of assigning the organic cofactors to one of the two groups is on the basis of the mechanism involved in their repetitive turnover in the functioning system.

  For repetitive turnover of Coenzymes, two substrates (in addition to Coenzyme) and two enzymes are needed. If only one enzyme or substrate is present, the Coenzyme will be used up in one passage through the system. Consider as an example the enzyme alcohol dehydrogenase (ADH) involved in the oxidation of ethanol to acetaldehyde.

  CH 3

  CH 2

  OH + NAD +

  ⇌ ADH

  CH 3

  CHO + NADH +

  H +

  (1)

  NAD+ (nicotinamide adenine dinucleotide) is an essential Coenzyme for the oxidation of ethanol to acetaldehyde. In the process, NAD+ is reduced to NADH, serving as the second substrate. NADH cannot function to convert more ethanol to acetaldehyde and thus is used up. For NAD+ to function in a repetitive fashion in vivo it must dissociate from alcohol dehydrogenase and reassociate with a second enzyme, which then uses the reduced Coenzyme to reduce a second substrate molecule. Equations (2) and (3)

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  eBook - PDF

  Color Atlas of Biochemistry

  • Jan Koolman, Klaus-Heinrich Röhm(Authors)
  • 2012(Publication Date)
  • Thieme

    (Publisher)

  At a certain temperature, the enzyme then becomes un-stable, and its activity is lost within a narrow temperature range as a result of denaturation (p. 60). The optimal temperatures of the en-zymes in higher organisms rarely exceed 50°C, while enzymes from thermophilic bacteria may still be active at 100°C. B. Coenzymes Enzymes that catalyze reactions in which groups are transferred usually require helper molecules called Coenzymes (p. 86ff.). Their function is to provide the group to be trans-ferred or accept it temporarily in the course of the reaction. As Coenzymes are not catalyti-cally active themselves, the less frequently used term “cosubstrate” would be more appro-priate. In contrast to substrates for which a given enzyme is specific (p. 72), Coenzymes cooperate with many enzymes of varying sub-strate specificity. Depending on the type of in -teraction with the enzyme, a distinction is made between soluble Coenzymes and pros-thetic groups. Soluble Coenzymes ( 1 ) are bound like substrates during a reaction, undergo a chemical change, and are then released again . The original form of the Coenzyme is regener-ated by a second, independent reaction. Pros-thetic groups ( 2 ), on the other hand, are coen-zymes that are tightly bound to the enzyme (sometimes covalently) and remain associated with it during the reaction. The part of the sub-strate bound by the Coenzyme after release of the first product is then transferred in a second reaction to another substrate or Coenzyme of the same enzyme. Many Coenzymes are aromatic compounds that cannot be synthesized from scratch by animal cells. Their precursors must therefore be provided in the diet as vitamins (p. 392f.). C. Metals as cofactors Metal ions can also serve as enzyme cofactors. Their functions are very varied; some stabilize the native conformation of the active center, while others are involved in redox reactions (p. 12) or facilitate catalysis by polarizing chemical bonds in the substrate.

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  eBook - ePub

  Biocatalysis

  Biochemical Fundamentals and Applications

  • Peter Grunwald(Author)
  • 2017(Publication Date)
  • WSPC (EUROPE)

    (Publisher)

  Chapter 4

  Non-protein Groups in Biocatalysis

  Frequently, enzymes develop their catalytic activity solely on the basis of a specific arrangement of some few amino acid residues. However, there are many others — about half of all known enzymes or even more — that need the assistance of cofactors of organic or inorganic origin which are metal ions in the latter case or small organic molecules, constituting a group of metabolites that after use in a biotransformation are regenerated. An impressive example is the ‘universal energy carrier’ adenosine triphosphate (ATP + H2 O → ADP + Pi + H+ ; ΔG pH=7 : ˗30.5 kJ/mol) present, e.g., in the human body in some few grams; however the amount of ATP regenerated per day from ADP and inorganic phosphate (Pi ) in the mitochondria approximately equals the body weight (Törnroth-Horsefield and Neutze, 2008). Orth et al. (2011) updated the genome-scale metabolic network reconstruction of E. coli and found ATP to be the most commonly used cofactor participating in 359 reactions, followed by ADP, NAD, NADH, NADP, NADPH and others (see also Meyer et al., 2014).

  A metal ion or another non-protein group that is bound covalently to an enzyme’s active site is termed prostetic group. These are usually distinguished from so-called Coenzymes that are organic molecules of low molecular weight — a differentiation not always kept consequently in the relevant literature. Many Coenzymes are in dissociation/association equilibrium with the catalysts and are modified during the reaction so that they rather have the function of a co-substrate; examples are NAD+ and NADH (the oxidized and the reduced form of nicotinamide adenine dinucleotide) that transfer hydride (H− ) ions. However, other Coenzymes as the electron transferring cofactors FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide) are bound to the respective enzyme rather tightly — sometimes even covalently as in case of the flavoprotein succinate dehydrogenase (EC 1.3.99.1), an enzyme complex that in a first step oxidizes succinate to fumarate with FAD as oxidant. Coenzymes in addition may contain a metal ion (Czerniecki and Czygier, 2001) that is coordinated by electron pair donating atoms; in some rare cases real metalorganic Mz+ –carbon bonds are formed. An active enzyme together with its essential metal ion and/or Coenzyme is named holoenzyme, and the protein portion apoenzyme. The following table provides an overview of the distribution of metal ions among the different enzyme classes (Andreini et al., 2008; more information about mechanisms of metalloenzymes are available from the Metal-MACiE database: http://www.ebi.ac.uk/thornton-srv/databases/Metal_MACiE/home.html

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  eBook - PDF

  Biochemical Engineering

  • Douglas S. Clark, Harvey W. Blanch(Authors)
  • 1997(Publication Date)
  • CRC Press

    (Publisher)

  Chapter 1. Enzyme Catalysis Enzymes are one of the essential components of all living systems. These macromo- lecules have a key role in catalyzing the chemical transformations that occur in all cell metabolism. The nature and specificity of their catalytic activity is primarily due to the three-dimensional structure of the folded protein, which is determined by the sequence of the amino acids that make up the enzyme. The activity of globular proteins may be regulated by one or more small molecules, which cause small conformational changes in the protein structure. Catalytic activity may depend on the action of these non-protein components (known as cofactors) associated with the protein. If the cofactor is an organic molecule, it is referred to as a Coenzyme. The catalytically inactive enzyme (without cofactor) is termed an apoenzyme; when Coenzyme or metal ion is added, the active enzyme is then termed a holoenzyme. Many cofactors are tightly bound to the enzyme and cannot be easily removed; they are then referred to as prosthetic groups. In this chapter we shall examine the nature of enzyme catalysis, first by examining the types of reactions catalyzed and the mechanisms employed by enzymes to effect this catalysis, and then by reviewing the common constitutive rate expressions which describe the kinetics of enzyme action. As we shall see, these can range from simple rate expressions to complex expressions that involve several reactants and account for modification of the enzyme structure. 1.1 Specificity of Enzyme Catalysis Enzymes have been classified into six main types, depending on the nature of the reaction catalyzed. A numbering scheme for enzymes has been developed, in which the main classes are distinguished by the first of four digits. The second and third digits describe the type of reaction catalyzed, and the fourth digit is employed to distinguish between enzymes of the same function on the basis of the actual substrate in the reaction catalyzed.

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  eBook - ePub

  Introduction to Nutrition and Metabolism

  • David A Bender, Shauna M C Cunningham(Authors)
  • 2021(Publication Date)
  • CRC Press

    (Publisher)

  in vitro without added Coenzyme permits measurement of what was initially present as holoenzyme, while incubation with substrate after the addition of Coenzyme permits activation (and hence measurement) of the apoenzyme. The increase in catalytic activity after addition of Coenzyme is the activation coefficient; for someone whose vitamin status is good, the activation coefficient will be only slightly greater than 1.0; the higher the activation coefficient (meaning that there is more apoenzyme without its Coenzyme), the poorer the subject’s vitamin status.

  Key Points

  • Breaking of covalent bonds requires an input of energy (the activation energy) to excite electrons to an unstable configuration.

  • Exothermic reactions proceed with output of heat, and endothermic reactions require an input of energy.

  • Enzymes catalyze reactions by lowering the activation energy; they increase the rate at which equilibrium is reached but do not affect the position of equilibrium. In vivo reactions are not normally at equilibrium because there is constant flux through the pathway.

  • The active site of an enzyme comprises a substrate-binding site and a catalytic site; both are formed by reactive groups in the side chains of amino acids that may be some distance apart in the primary sequence of the protein.

  • Enzymes show considerable specificity for the substrates bound and the reaction catalyzed.

  • Enzymes may have nonprotein components, Coenzymes or prosthetic groups that may be covalently or noncovalently bound to the protein and are essential for activity.

  • Most enzymes show a hyperbolic relationship between the concentration of substrate and the rate of reaction; V max is the maximum rate of reaction when the enzyme is saturated with substrate.

  • K m is an inverse measure of the affinity of an enzyme for its substrate; it is the concentration of substrate at which the enzyme achieves half V max .

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