Enzyme Cofactor

8 Key excerpts on "Enzyme Cofactor"

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  eBook - ePub

  Chemistry of Biomolecules, Second Edition

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

    (Publisher)

  Some enzymes in order to exhibit catalytic reactivity require additional chemical compounds called cofactors. Cofactors are molecules that attach to an enzyme during chemical reactions. In general, all compounds that help enzymes in their catalytic reactivity are called cofactors. A cofactor is any non-protein component in an enzyme. It is an organic molecule or metal ion which the enzyme requires in order to catalyse a reaction.

  We have seen that most enzymes are simple globular proteins. Some others are conjugated proteins which have a non-protein fraction called the prosthetic group. A prosthetic group is an essential cofactor attached to the protein part of a conjugated enzyme. That means cofactors which are bound tightly to an enzyme are termed as prosthetic groups. These can be organic vitamins, sugars, lipids etc.

  An enzyme without a cofactor is called an apoenzyme and the enzyme-cofactor complex is called a holoenzyme. Apoenzyme is enzymatically an inactive protein. Cofactors can be divided into two groups.

  •  Organic cofactors, which are called coenzymes. •  Inorganic cofactors – essential metal ions.

  B.  Coenzymes

  Organic cofactors are known as coenzymes. A coenzyme is an organic non-protein compound that binds with an enzyme to catalyse a reaction.

  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

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  eBook - ePub

  Protein Engineering Handbook, Volume 3

  Volume 3

  • Stefan Lutz, Uwe Theo Bornscheuer(Authors)
  • 2012(Publication Date)
  • Wiley-VCH

    (Publisher)

  8 Enzyme Engineering by Cofactor Redesign Malgorzata M. Kopacz, Frank. Hollmann, and Marco W. Fraaije

  8.1 Introduction

  Enzymes catalyze a wide range of chemical reactions in nature, for which helper molecules – cofactors – are often employed. Cofactors are non-protein small molecules or atoms that are required in the active site of enzymes and are directly involved in catalysis. Cofactors thus extend the scope of chemistry in nature beyond what is feasible when using only amino acids. Although more than half of all known enzymes use such “helper molecules” [1], the actual number of natural cofactors is, nevertheless, limited. In order to broaden the catalytic potential of enzymes, recent protein engineering approaches have been expanded to develop, and subsequently employ, enzymes containing redesigned cofactors.

  It is assumed that many natural organic cofactors have evolved from ribozymes, which are catalytic RNA molecules. The discovery of RNA-based catalysis brought an end to the idea that enzymes are the only natural catalytic machineries, and placed RNA before DNA and proteins in the evolution of life [2, 3]. It is hypothesized that around four billion years ago, in the so-called “RNA world,” a collection of RNAs or RNA-like molecules could function as a carrier of genetic information and as a catalyst of essential chemical reactions [4–6]. It is interesting to note that some of the most common contemporary Enzyme Cofactors, such as nicotinamide adenine dinucleotide (NAD) and flavin adenine dinucleotide (FAD), are derivatives of ribonucleotides. Furthermore, it has been found that several of the most ubiquitous cofactors can be targets for riboswitches [7–17], which are functional RNA molecules able to directly sense and regulate levels of cellular metabolites [18]. Therefore, it is speculated that cofactors were actually first utilized by ribozymes. For example, it has been proposed that NAD+ and NADP+

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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

  How Enzymes Work

  From Structure to Function

  • Haruo Suzuki(Author)
  • 2019(Publication Date)
  • Jenny Stanford Publishing

    (Publisher)

  Chapter 7

  Cofactors

  Chapter 6 described the structure of protein. This chapter describes the regions related to the protein function. The first half of the chapter deals with familiar cofactors in the biochemistry textbook. The rest deals with cofactors formed via post-translational modification of enzyme active site. These cofactors may be unfamiliar to the reader, but widen the enzyme function. There are many cofactors, but I could not cover the whole here, since to include all the cofactors is beyond the scope of this book. Let’s start with some definition.

  7.1    Active Site and Active Center

  In the previous chapters, the term active site was used without definition. The active site means the region (area or place) of enzyme protein where substrate binds and is transformed to product. For the same meaning, the active center has been used. The “center” means “point.” However, accumulation of 3D structures of enzyme has shown that the region of enzyme related to the function is broad in space. Therefore, it seems better to use the term “active site.”

  7.2    Cofactor, Coenzyme, Prosthetic Group

  The active site of enzyme is usually composed of several amino acid residues. However, various enzymes also require metal ions, and/or organic groups for the activities. The terms used to denote these groups seem to be slightly different from one book to another. Here, the following usage is applied in this book. A cofactor means substances required for the activity of enzyme. The cofactor includes metal ions, coenzyme, and prosthetic groups [1 ].

  Coenzyme binds with the enzyme protein reversibly, and acts like substrate. Prosthetic group is an organic compound, binds strongly with enzyme, and is usually present as a protein-bound form. The cofactor-bound enzyme (protein) is called holoenzyme (holoprotein), and the cofactor-unbound enzyme (protein) is apoenzyme (apoprotein). Table 7.1

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  eBook - PDF

  Introduction to Peptides and Proteins

  • Ulo Langel, Benjamin F. Cravatt, Astrid Graslund, N.G.H. von Heijne, Matjaz Zorko, Tiit Land, Sherry Niessen(Authors)
  • 2009(Publication Date)
  • CRC Press

    (Publisher)

  Examples of metal ion cofactor and some enzymes for which they are required are listed in Table 21.2. Metal ions shown in this table appear to be needed by all organisms, including human, but some organisms, par-ticularly microorganisms, also require other ions, including ions of Cd, V, and W. Coenzymes and prosthetic groups are organic molecules that can temporarily bind specific functional group or electron(s) during the catalytic process in which this group is transferred between substrates. Prosthetic groups are tightly and perma-nently bound to the protein, and are an integral part of the enzyme where they accept a functional group or electron(s) in one catalytic process and release it in another. In contrast to this, coenzymes are promiscuous. They bind transiently and rather weakly to the enzyme, where they accept a functional group from the substrate. Then they are released and subsequently bound to another enzyme where they pass the functional group to another substrate and are recovered. In this, coenzymes resemble substrates and are sometimes treated as such. Indeed, in the two- and three-substrate enzyme reactions discussed above (see Section 21.4.2), one or sometimes even two substrates are actually coenzymes. An example is shown in Equations 21.18–21.20 TABLE 21.2 Some Examples of Metal Ions as Enzyme Cofactors Metal Ion Enzymes Fe 2 + /Fe 3 + Cytochrome oxidase, catalase, nitrogenase, hydrogenase Zn 2 + Carboxypeptidases, alcohol dehydrogenase, carbonic anhydrase Cu 2 + Cytochrome oxidase, hexose oxidase, nitrite reductase Mg 2 + Hexokinase, pyruvate kinase, glucose-6-phosphatase Mn 2 + Ribonucleotide reductase, arginase, water-splitting enzyme (photosynthesis) Ni 2 + Urease, carbon monoxide dehydrogenase Se Glutathione peroxidase, formate dehydrogenase Mo Dinitrogenase, sulfite oxidase, nitrate reductase Note: Hundreds of enzymes need metal ions as cofactors.

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  Medical Biochemistry

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

    (Publisher)

  ribozymes (p. 501).

  Current techniques have allowed us to understand the exact structure and build accurate models of many enzymes. This has shed light on the mechanism of enzyme action. Some enzymes are composed by only amino acids. Hydrolases, in general, are simple proteins. Other enzymes are formed by the association of various subunits or polypeptide chains, constituting oligomers. Often, the association between the subunits that form an enzyme is of functional significance.

  Coenzyme . Many enzymes only perform their catalytic role when associated with another nonprotein molecule, of relatively small size, called a coenzyme . Coenzymes can be firmly attached to the enzyme by covalent or other strong bonds, forming complexes that are difficult to separate. Some authors prefer to call them prosthetic groups and reserve the name coenzyme for those chemical groups that are more loosely associated to the protein. In this textbook, the name coenzyme will be used indistinctly. Both the protein and nonprotein portions are essential for enzyme activity. The entire system is called holoenzyme and consists of the protein or apoenzyme (a macromolecule, thermolabile and nondialyzable) and the coenzyme (nonprotein molecule, thermostable and of relatively small size).

  Oxidoreductases, transferases, isomerases, and ligases require coenzymes. These are actively involved in the reaction, undergoing changes that compensate for the transformation undergone by the substrate. For example, the coenzymes in oxidoreductases accept or transfer the hydrogens or electrons subtracted from or donated to the substrate. Transferases have coenzymes, which accept or donate the group transferred in the reaction.

  Many coenzymes present structures that resemble nucleotides. Moreover, coenzymes are related to vitamins , compounds that the body cannot synthesize and must be supplied with the diet. B complex vitamins function as coenzymes themselves or form part of the structure of coenzymes. This participation in enzymatic processes gives many vitamins their physiological importance. Table 8.1 lists different coenzymes and the vitamin they are related to. The functional role of vitamins will be described in Chapter 27

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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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  Bioinorganic Catalysis

  • Jan Reedijk, Elisabeth Bouwman, Jan Reedijk, Elisabeth Bouwman(Authors)
  • 1999(Publication Date)
  • CRC Press

    (Publisher)

  16 Metalloenzymes with a Quinone Cofactor Johannis A. Duine Delft University of Technology, Delft, The Netherlands I. INTRODUCTION About half of the enzymes known today require the presence of a cofactor, coen-zyme, or prosthetic group, such a compound plays a direct role in catalysis by the enzyme in which it occurs (in the following, the term cofactor also comprises the connotation of a prosthetic group but not that of a coenzyme, as the latter is considered here to be a helper or cosubstrate in the reaction). In the past, identifi-cation of these compounds has been a matter of combined action of nutritional and biochemical research, this approach ended about 30 years ago as it was thought that all existing coenzymes, cofactors, and vitamins had been discovered. It was, therefore, a surprise when it subsequently appeared that the list should be extended because of results provided by research on the enzymology of methane dissimilation by methanotrophic bacteria and that on methane formation by meth-anogenic bacteria, generating several new cofactors [1]. However, most of them seemed to have a specialized role in Archaea, although it appears now that this view should not be taken too strictly (e.g., factor 420 , a deazaflavin with very low redox potential that on its discovery was considered ideally suited to have a role only in the pathway of methanogenesis, has now been found to function as a cofactor in several enzymes occurring in aerobic Eubacteria [2]). Soon after its discovery in methanol dehydrogenase, pyrroloquinoline quinone, 2,7,9-tricar-boxy-1H-pyrrolo[2,3-f]quinoline-4,5-dione (PQQ) (Figure 1), appeared to be ex-ceptional in that sense that it was found in several different bacterial dehydrog-enases (Table 1). Subsequently, many other enzymes were detected and were at 563 564 Duine 0 (1) (2) (3) (4) Figure 1 Structures of PQQ (1), TTQ (2), TPQ (3), and LTQ (4).

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