Chemistry
Inorganic Cofactors
Inorganic cofactors are non-protein chemical compounds that assist enzymes in catalyzing biochemical reactions. They often function as electron carriers or participate in redox reactions. Inorganic cofactors can be metal ions or small inorganic molecules, and they play crucial roles in various biological processes.
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8 Key excerpts on "Inorganic Cofactors"
eBook - ePub- 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.Organic cofactors are known as coenzymes. A coenzyme is an organic non-protein compound that binds with an enzyme to catalyse a reaction.B. Coenzymes
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
eBook - ePub- Stefan Lutz, Uwe Theo Bornscheuer(Authors)
- 2012(Publication Date)
- Wiley-VCH(Publisher)
In general, metal ions are most active in the area of electrostatic stabilization and are more potent than amino acids – but not than organic cofactors – in pair and single-electron shuttling. Organic cofactors are able to support a wide range of reaction types, with many organic cofactors being involved in electron-transfer processes. This is in agreement with the fact that 80% of all oxidoreductases employ an organic cofactor.A given cofactor can perform a mechanistically identical reaction in various enzyme scaffolds (e.g., NAD for hydride transfer), or its mechanism of action can depend on the protein (e.g., S -adenosylmethionine as a methyl donor or radical generator) [27]. It is also possible that some cofactors occur only in one enzyme, such as dipyromethane in hydroxymethylbilane synthase (see Table 8.1 ), while some enzymes or enzyme complexes employ several cofactors. For example, formylmethanofuran dehydrogenase is composed of three subunits containing, respectively, a flavin, an iron-sulfur cluster, and two molybdopterin guanine dinucleotide cofactors coordinated to a tungstate [32].Table 8.1 Overview of known organic enzyme cofactors.Based on the CoFactor database [31]), October 2011.8.3 Inorganic Cofactors
Information concerning the properties and roles of metal ions involved in catalysis of metal-dependent enzymes is available in the Metal-MACiE database [29]. An analysis of specific chemical functions of metal cofactors, based on the database and structural information, has been summarized by Andreini et al . [28], according to whom oxidoreductases (EC 1) mostly use metals, especially iron, as their redox centers. When a metal is used as a redox catalyst, it is usually bound to an organic cofactor (e.g., iron in heme), but this is not the case in non-redox catalysis. Metal ions in transferases (EC 2) are mostly electrostatic stabilizers and/or activators, and increase the electrophilicity of the substrate so that nucleophilic substitution/addition becomes possible. Transferases most often utilize magnesium as their cofactors.In the case of hydrolases (EC 3) and lyases (EC 4), no redox-active metals are employed. Rather, metals in hydrolases either activate the substrate or stabilize the electrostatic charge, with zinc appearing to be the most suitable metal for both functions. The role of metals in lyases is to induce proton transfer from the substrate; magnesium and zinc are each used for this purpose, based on their ability to enhance the acidity of the substrate.
eBook - ePub- John R. Whitaker(Author)
- 2018(Publication Date)
- Routledge(Publisher)
12Enzyme CofactorsI. 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.(1)CH 3CH 2OH + NAD +⇌ ADHCH 3CHO + NADH +H +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)
eBook - ePubBiocatalysis
Biochemical Fundamentals and Applications
- Peter Grunwald(Author)
- 2017(Publication Date)
- WSPC (EUROPE)(Publisher)
Chapter 4Non-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
eBook - ePubHow Enzymes Work
From Structure to Function
- Haruo Suzuki(Author)
- 2019(Publication Date)
- Jenny Stanford Publishing(Publisher)
Chapter 7Cofactors
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
eBook - ePubBiomass, Biofuels, Biochemicals
Advances in Enzyme Catalysis and Technologies
- Sudhir P. Singh, Ashok Pandey, Reeta Rani Singhania, Christian Larroche, Zhi Li(Authors)
- 2020(Publication Date)
- Elsevier(Publisher)
[10] . The charged and/or polar residues participate in charge stabilization and exchange of electrons and protons. The catalytic residues are conserved and have structural rigidity over other residues in the enzyme. Such features make an enzyme, specific toward the substrate.1.2.2 Cofactor, a necessity of enzyme
Another vital aspect of the enzyme, which distinguishes it from protein, is the requirement of a non-protein substance called as cofactors, the essential component for execution of catalytic reaction. Cofactors can further be categorized into prosthetic groups and coenzymes, depending on their type of association with the enzymes [5] . Prosthetic groups are a small molecule, which remains bound to the enzyme; for example, heme is bound to myoglobin and hemoglobin protein as an essential component for oxygen binding. In some cases, metal ions (such as zinc or iron) remain bound to the enzymes, playing a critical role in the catalysis. Coenzymes carry chemical groups; for example, nicotinamide adenine dinucleotide (NAD+ ) functions as an electron carrier in oxidation–reduction reactions [9] . Interestingly, the presence of cofactor can induce conformational changes in the enzyme that may increase the fitting and interaction of the substrate with the active site [11] .1.3 What is enzyme catalysis?
1.3.1 Basics of enzyme catalysis
Enzyme catalysis plays a vital role in the metabolism of all the living organisms. Enzymatic reactions are like chemical reactions, which result in the product, and the free energy change (ΔG ) during this process is negative. However, the rate of reaction depends on another factor, known as activation energy (EA). If the ΔG is favorable, but still the need of high EA leads to slower progression of the reaction. The biological reaction is required to be catalyzed in the fractions of a second [12] . The slower biochemical changes are made faster (1010 –1020 ) by using the enzymatic actions, without which a reaction may take millions of years to complete [13]
eBook - PDFInorganic Biochemistry
Volume 1
- H A O Hill(Author)
- 2007(Publication Date)
- Royal Society of Chemistry(Publisher)
the activation of amino-acid residues in proteins, the co-ordination and polarization of substrates, coenzymes, solvent, etc., or any combination of these. Most metal ions can function in this manner, albeit less effectively, in simple co-ordination compounds. However, in biology, though all may be called, few are chosen. For example, the Lewis acidity (assuming this is relevant) of copper(@ ion is at least the equal of any other bivalent cation of the fist tran- sition series. Though copper plays a major role in many electron-transfer pro- cesses, it does not appear to function in any non-redox metalloprotein. The simplest rationale of the selection of metal ions for metalloenzymeswould be that those metal ions which can readily take part in redox reactions under normal biological conditions are excluded from those proteins in which they would be required to have a role related to their Lewis acidity. Obviously there are excep- tions to this generalization, such as cobalt(@ in oxaloacetate transcarboxylases from P. shermanii.l Nevertheless it appears that biology has chosen to use magnesium(II), calcium(n), manganese@), nickel(@, and first and foremost zinc(@ to fulfill the role of Lewis acids in metalloenzymes. [The redox chemistry of manganese(@ and nickel(@ is not readily expressed under ‘normal’ biological conditions, though it is possible to alter the redox chemistry by co-ordination. Thus the role of manganese in superoxide dismutase or in the chloroplast is presumably related to its redox chemistry.] Of these ions, zinc@) plays the most important role in metalloenzymes, as opposed2to metaZ-activated enzymes.
eBook - ePubThe Chemistry of Evolution
The Development of our Ecosystem
- R.J.P Williams, J.J.R Fraústo da Silva(Authors)
- 2005(Publication Date)
- Elsevier Science(Publisher)
The organic chemicals of organisms are a special set of such small molecules and polymers of various kinds soluble in water. In essence they are formed by the action of light. (9) The inorganic elements in aqueous solution reactions, both acid–base complex formation, precipitation and oxidation/reduction, frequently come rapidly to equilibrium when no more reactions are possible. The implication is that in the environment and in organisms many of their properties cannot change unless circumstances change, for example the introduction of new components. (10) The reactions of the organic chemicals (see (7)) in chemical laboratories and organisms are generally controlled by bound inorganic metal elements, catalysts. Heavy non-metals such as sulfur and phosphorus are also advantageous as carriers and catalyst centres of small organic groups for synthetic purposes due to their intermediate reactivity between light non-metals and metal ions. Catalysis is at the heart of biological activity. (11) Overall these conclusions concerning chemistry mean that an ecological system of the following restricted kind can be generated and can evolve. In the fully cyclic condition the system is element neutral The next chapter will discuss the nature of energy and the ways in which it can be incorporated into chemicals using the basic principles of chemistry and geochemistry set out in Chapters 1 and 2 so as to create what we know as a system called life locked into the environment, the total ecosystem. (Note : Heat is given out in small amounts even in the forward step but we shall ignore it here and elsewhere.) Importantly notice that equilibria limit the diversity of particularly inorganic compounds and complexes but are not usually relevant to the discussion of the properties of organic compounds although they are relevant to certain organic chemical complexes
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