Information

Do non-enzyme catalysed reaction pathways exist?


Can their be a kind of chemical reaction pathway in a cell, that is catalyzed or regulated but NOT necessarily by enzymes? I could not find anything on Google.

I have almost no background in biology, and am only studying certain topics from a mathematical perspective.


If by enzyme you mean "protein" aka polypeptide, than there are such things as catalitic RNAs. Those are molecules of RNA that facilitate chemical reactions but don't change themselves (definition of catalyst). I think that, based on the discovery of such RNAs, it is now believed that life might have started from or with the help of catalytic RNAs (please forgive the speculative tone, see self-replicating RNAs).

You might find this article interesting: The Road to Non-Enzymatic Molecular Networks, which describes non-enzymatic networks. The problem with searching this topic is that most current publications, seem to me, to concentrate on way to transfer enzymatic reactions into inorganic catalysis systems--because those systems can be more clean and easy to expand--than purifying enzymes for biotech.


Cellulase

Cellulase is any of several enzymes produced chiefly by fungi, bacteria, and protozoans that catalyze cellulolysis, the decomposition of cellulose and of some related polysaccharides. The name is also used for any naturally occurring mixture or complex of various such enzymes, that act serially or synergistically to decompose cellulosic material.

Cellulases break down the cellulose molecule into monosaccharides ("simple sugars") such as beta-glucose, or shorter polysaccharides and oligosaccharides. Cellulose breakdown is of considerable economic importance, because it makes a major constituent of plants available for consumption and use in chemical reactions. The specific reaction involved is the hydrolysis of the 1,4-beta-D-glycosidic linkages in cellulose, hemicellulose, lichenin, and cereal beta-D-glucans. Because cellulose molecules bind strongly to each other, cellulolysis is relatively difficult compared to the breakdown of other polysaccharides such as starch. [2]

Most mammals have only very limited ability to digest dietary fibres like cellulose by themselves. In many herbivorous animals such as ruminants like cattle and sheep and hindgut fermenters like horses, cellulases are produced by symbiotic bacteria. Endogenous cellulases are produced by a few types of metazoan animals, such as some termites, snails, [3] [4] [5] and earthworms.

Recently, cellulases have also been found in green microalgae (Chlamydomonas reinhardtii, Gonium pectorale and Volvox carteri) and their catalytic domains (CD) belonging to GH9 Family show highest sequence homology to metazoan endogenous cellulases. Algal cellulases are modular, consisting of putative novel cysteine-rich carbohydrate-binding modules (CBMs), proline/serine-(PS) rich linkers in addition to putative Ig-like and unknown domains in some members. Cellulase from Gonium pectorale consisted of two CDs separated by linkers and with a C-terminal CBM. [6]

Several different kinds of cellulases are known, which differ structurally and mechanistically. Synonyms, derivatives, and specific enzymes associated with the name "cellulase" include endo-1,4-beta-D-glucanase (beta-1,4-glucanase, beta-1,4-endoglucan hydrolase, endoglucanase D, 1,4-(1,3,1,4)-beta-D-glucan 4-glucanohydrolase), carboxymethyl cellulase (CMCase), avicelase, celludextrinase, cellulase A, cellulosin AP, alkali cellulase, cellulase A 3, 9.5 cellulase, and pancellase SS. Enzymes that cleave lignin have occasionally been called cellulases, but this old usage is deprecated they are lignin-modifying enzymes.


Do non-enzyme catalysed reaction pathways exist? - Biology

Figure 1. Enzymes lower the activation energy of the reaction but do not change the free energy of the reaction.

A substance that helps a chemical reaction to occur is called a catalyst, and the molecules that catalyze biochemical reactions are called enzymes. Most enzymes are proteins and perform the critical task of lowering the activation energies of chemical reactions inside the cell. Most of the reactions critical to a living cell happen too slowly at normal temperatures to be of any use to the cell. Without enzymes to speed up these reactions, life could not persist. Enzymes do this by binding to the reactant molecules and holding them in such a way as to make the chemical bond-breaking and -forming processes take place more easily. It is important to remember that enzymes do not change whether a reaction is exergonic (spontaneous) or endergonic. This is because they do not change the free energy of the reactants or products. They only reduce the activation energy required for the reaction to go forward (Figure 1). In addition, an enzyme itself is unchanged by the reaction it catalyzes. Once one reaction has been catalyzed, the enzyme is able to participate in other reactions.

The chemical reactants to which an enzyme binds are called the enzyme’s substrates. There may be one or more substrates, depending on the particular chemical reaction. In some reactions, a single reactant substrate is broken down into multiple products. In others, two substrates may come together to create one larger molecule. Two reactants might also enter a reaction and both become modified, but they leave the reaction as two products. The location within the enzyme where the substrate binds is called the enzyme’s active site. The active site is where the “action” happens. Since enzymes are proteins, there is a unique combination of amino acid side chains within the active site. Each side chain is characterized by different properties. They can be large or small, weakly acidic or basic, hydrophilic or hydrophobic, positively or negatively charged, or neutral. The unique combination of side chains creates a very specific chemical environment within the active site. This specific environment is suited to bind to one specific chemical substrate (or substrates).

Active sites are subject to influences of the local environment. Increasing the environmental temperature generally increases reaction rates, enzyme-catalyzed or otherwise. However, temperatures outside of an optimal range reduce the rate at which an enzyme catalyzes a reaction. Hot temperatures will eventually cause enzymes to denature, an irreversible change in the three-dimensional shape and therefore the function of the enzyme. Enzymes are also suited to function best within a certain pH and salt concentration range, and, as with temperature, extreme pH, and salt concentrations can cause enzymes to denature.

For many years, scientists thought that enzyme-substrate binding took place in a simple “lock and key” fashion. This model asserted that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a model called induced fit (Figure 2). The induced-fit model expands on the lock-and-key model by describing a more dynamic binding between enzyme and substrate. As the enzyme and substrate come together, their interaction causes a mild shift in the enzyme’s structure that forms an ideal binding arrangement between enzyme and substrate.

When an enzyme binds its substrate, an enzyme-substrate complex is formed. This complex lowers the activation energy of the reaction and promotes its rapid progression in one of multiple possible ways. On a basic level, enzymes promote chemical reactions that involve more than one substrate by bringing the substrates together in an optimal orientation for reaction. Another way in which enzymes promote the reaction of their substrates is by creating an optimal environment within the active site for the reaction to occur.

Figure 2. The induced-fit model is an adjustment to the lock-and-key model and explains how enzymes and substrates undergo dynamic modifications during the transition state to increase the affinity of the substrate for the active site.

Careers in Action: Pharmaceutical Drug Developer

Figure 3. Have you ever wondered how pharmaceutical drugs are developed? (credit: Deborah Austin)

Enzymes are key components of metabolic pathways. Understanding how enzymes work and how they can be regulated are key principles behind the development of many of the pharmaceutical drugs on the market today. Biologists working in this field collaborate with other scientists to design drugs.

Consider statins for example—statins is the name given to one class of drugs that can reduce cholesterol levels. These compounds are inhibitors of the enzyme HMG-CoA reductase, which is the enzyme that synthesizes cholesterol from lipids in the body. By inhibiting this enzyme, the level of cholesterol synthesized in the body can be reduced. Similarly, acetaminophen, popularly marketed under the brand name Tylenol, is an inhibitor of the enzyme cyclooxygenase. While it is used to provide relief from fever and inflammation (pain), its mechanism of action is still not completely understood.

How are drugs discovered? One of the biggest challenges in drug discovery is identifying a drug target. A drug target is a molecule that is literally the target of the drug. In the case of statins, HMG-CoA reductase is the drug target. Drug targets are identified through painstaking research in the laboratory. Identifying the target alone is not enough scientists also need to know how the target acts inside the cell and which reactions go awry in the case of disease. Once the target and the pathway are identified, then the actual process of drug design begins. In this stage, chemists and biologists work together to design and synthesize molecules that can block or activate a particular reaction. However, this is only the beginning: If and when a drug prototype is successful in performing its function, then it is subjected to many tests from in vitro experiments to clinical trials before it can get approval from the U.S. Food and Drug Administration to be on the market.

Many enzymes do not work optimally, or even at all, unless bound to other specific non-protein helper molecules. They may bond either temporarily through ionic or hydrogen bonds, or permanently through stronger covalent bonds. Binding to these molecules promotes optimal shape and function of their respective enzymes. Two examples of these types of helper molecules are cofactors and coenzymes. Cofactors are inorganic ions such as ions of iron and magnesium. Coenzymes are organic helper molecules, those with a basic atomic structure made up of carbon and hydrogen. Like enzymes, these molecules participate in reactions without being changed themselves and are ultimately recycled and reused. Vitamins are the source of coenzymes. Some vitamins are the precursors of coenzymes and others act directly as coenzymes. Vitamin C is a direct coenzyme for multiple enzymes that take part in building the important connective tissue, collagen. Therefore, enzyme function is, in part, regulated by the abundance of various cofactors and coenzymes, which may be supplied by an organism’s diet or, in some cases, produced by the organism.


6.5 Enzymes

A substance that helps a chemical reaction to occur is a catalyst, and the special molecules that catalyze biochemical reactions are called enzymes. Almost all enzymes are proteins, made up of chains of amino acids, and they perform the critical task of lowering the activation energies of chemical reactions inside the cell. Enzymes do this by binding to the reactant molecules, and holding them in such a way as to make the chemical bond-breaking and bond-forming processes take place more readily. It is important to remember that enzymes don’t change the ∆G of a reaction. In other words, they don’t change whether a reaction is exergonic (spontaneous) or endergonic. This is because they don’t change the free energy of the reactants or products. They only reduce the activation energy required to reach the transition state (Figure 6.15).

Enzyme Active Site and Substrate Specificity

The chemical reactants to which an enzyme binds are the enzyme’s substrates . There may be one or more substrates, depending on the particular chemical reaction. In some reactions, a single-reactant substrate is broken down into multiple products. In others, two substrates may come together to create one larger molecule. Two reactants might also enter a reaction, both become modified, and leave the reaction as two products. The location within the enzyme where the substrate binds is called the enzyme’s active site . The active site is where the “action” happens, so to speak. Since enzymes are proteins, there is a unique combination of amino acid residues (also called side chains, or R groups) within the active site. Each residue is characterized by different properties. Residues can be large or small, weakly acidic or basic, hydrophilic or hydrophobic, positively or negatively charged, or neutral. The unique combination of amino acid residues, their positions, sequences, structures, and properties, creates a very specific chemical environment within the active site. This specific environment is suited to bind, albeit briefly, to a specific chemical substrate (or substrates). Due to this jigsaw puzzle-like match between an enzyme and its substrates (which adapts to find the best fit between the transition state and the active site), enzymes are known for their specificity. The “best fit” results from the shape and the amino acid functional group’s attraction to the substrate. There is a specifically matched enzyme for each substrate and, thus, for each chemical reaction however, there is flexibility as well.

The fact that active sites are so perfectly suited to provide specific environmental conditions also means that they are subject to influences by the local environment. It is true that increasing the environmental temperature generally increases reaction rates, enzyme-catalyzed or otherwise. However, increasing or decreasing the temperature outside of an optimal range can affect chemical bonds within the active site in such a way that they are less well suited to bind substrates. High temperatures will eventually cause enzymes, like other biological molecules, to denature , a process that changes the natural properties of a substance. Likewise, the pH of the local environment can also affect enzyme function. Active site amino acid residues have their own acidic or basic properties that are optimal for catalysis. These residues are sensitive to changes in pH that can impair the way substrate molecules bind. Enzymes are suited to function best within a certain pH range, and, as with temperature, extreme pH values (acidic or basic) of the environment can cause enzymes to denature.

Induced Fit and Enzyme Function

For many years, scientists thought that enzyme-substrate binding took place in a simple “lock-and-key” fashion. This model asserted that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view called induced fit (Figure 6.16). The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes a mild shift in the enzyme’s structure that confirms an ideal binding arrangement between the enzyme and the transition state of the substrate. This ideal binding maximizes the enzyme’s ability to catalyze its reaction.

Link to Learning

View an animation of induced fit at this website.

When an enzyme binds its substrate, an enzyme-substrate complex is formed. This complex lowers the activation energy of the reaction and promotes its rapid progression in one of many ways. On a basic level, enzymes promote chemical reactions that involve more than one substrate by bringing the substrates together in an optimal orientation. The appropriate region (atoms and bonds) of one molecule is juxtaposed to the appropriate region of the other molecule with which it must react. Another way in which enzymes promote the reaction of their substrates is by creating an optimal environment within the active site for the reaction to occur. Certain chemical reactions might proceed best in a slightly acidic or non-polar environment. The chemical properties that emerge from the particular arrangement of amino acid residues within an active site create the perfect environment for an enzyme’s specific substrates to react.

You’ve learned that the activation energy required for many reactions includes the energy involved in manipulating or slightly contorting chemical bonds so that they can easily break and allow others to reform. Enzymatic action can aid this process. The enzyme-substrate complex can lower the activation energy by contorting substrate molecules in such a way as to facilitate bond-breaking, helping to reach the transition state. Finally, enzymes can also lower activation energies by taking part in the chemical reaction itself. The amino acid residues can provide certain ions or chemical groups that actually form covalent bonds with substrate molecules as a necessary step of the reaction process. In these cases, it is important to remember that the enzyme will always return to its original state at the completion of the reaction. One of the hallmark properties of enzymes is that they remain ultimately unchanged by the reactions they catalyze. After an enzyme is done catalyzing a reaction, it releases its product(s).

Control of Metabolism Through Enzyme Regulation

It would seem ideal to have a scenario in which all of the enzymes encoded in an organism’s genome existed in abundant supply and functioned optimally under all cellular conditions, in all cells, at all times. In reality, this is far from the case. A variety of mechanisms ensure that this does not happen. Cellular needs and conditions vary from cell to cell, and change within individual cells over time. The required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and functionality of different enzymes.

Since the rates of biochemical reactions are controlled by activation energy, and enzymes lower and determine activation energies for chemical reactions, the relative amounts and functioning of the variety of enzymes within a cell ultimately determine which reactions will proceed and at which rates. This determination is tightly controlled. In certain cellular environments, enzyme activity is partly controlled by environmental factors, like pH and temperature. There are other mechanisms through which cells control the activity of enzymes and determine the rates at which various biochemical reactions will occur.

Regulation of Enzymes by Molecules

Enzymes can be regulated in ways that either promote or reduce their activity. There are many different kinds of molecules that inhibit or promote enzyme function, and various mechanisms exist for doing so. In some cases of enzyme inhibition, for example, an inhibitor molecule is similar enough to a substrate that it can bind to the active site and simply block the substrate from binding. When this happens, the enzyme is inhibited through competitive inhibition , because an inhibitor molecule competes with the substrate for active site binding (Figure 6.17). On the other hand, in noncompetitive inhibition, an inhibitor molecule binds to the enzyme in a location other than an allosteric site and still manages to block substrate binding to the active site.

Some inhibitor molecules bind to enzymes in a location where their binding induces a conformational change that reduces the affinity of the enzyme for its substrate. This type of inhibition is called allosteric inhibition (Figure 6.18). Most allosterically regulated enzymes are made up of more than one polypeptide, meaning that they have more than one protein subunit. When an allosteric inhibitor binds to an enzyme, all active sites on the protein subunits are changed slightly such that they bind their substrates with less efficiency. There are allosteric activators as well as inhibitors. Allosteric activators bind to locations on an enzyme away from the active site, inducing a conformational change that increases the affinity of the enzyme’s active site(s) for its substrate(s).

Everyday Connection

Drug Discovery by Looking for Inhibitors of Key Enzymes in Specific Pathways

Enzymes are key components of metabolic pathways. Understanding how enzymes work and how they can be regulated is a key principle behind the development of many of the pharmaceutical drugs (Figure 6.19) on the market today. Biologists working in this field collaborate with other scientists, usually chemists, to design drugs.

Consider statins for example—which is the name given to the class of drugs that reduces cholesterol levels. These compounds are essentially inhibitors of the enzyme HMG-CoA reductase. HMG-CoA reductase is the enzyme that synthesizes cholesterol from lipids in the body. By inhibiting this enzyme, the levels of cholesterol synthesized in the body can be reduced. Similarly, acetaminophen, popularly marketed under the brand name Tylenol, is an inhibitor of the enzyme cyclooxygenase. While it is effective in providing relief from fever and inflammation (pain), its mechanism of action is still not completely understood.

How are drugs developed? One of the first challenges in drug development is identifying the specific molecule that the drug is intended to target. In the case of statins, HMG-CoA reductase is the drug target. Drug targets are identified through painstaking research in the laboratory. Identifying the target alone is not sufficient scientists also need to know how the target acts inside the cell and which reactions go awry in the case of disease. Once the target and the pathway are identified, then the actual process of drug design begins. During this stage, chemists and biologists work together to design and synthesize molecules that can either block or activate a particular reaction. However, this is only the beginning: both if and when a drug prototype is successful in performing its function, then it must undergo many tests from in vitro experiments to clinical trials before it can get FDA approval to be on the market.

Many enzymes don’t work optimally, or even at all, unless bound to other specific non-protein helper molecules, either temporarily through ionic or hydrogen bonds or permanently through stronger covalent bonds. Two types of helper molecules are cofactors and coenzymes . Binding to these molecules promotes optimal conformation and function for their respective enzymes. Cofactors are inorganic ions such as iron (Fe++) and magnesium (Mg++). One example of an enzyme that requires a metal ion as a cofactor is the enzyme that builds DNA molecules, DNA polymerase, which requires bound zinc ion (Zn++) to function. Coenzymes are organic helper molecules, with a basic atomic structure made up of carbon and hydrogen, which are required for enzyme action. The most common sources of coenzymes are dietary vitamins (Figure 6.20). Some vitamins are precursors to coenzymes and others act directly as coenzymes. Vitamin C is a coenzyme for multiple enzymes that take part in building the important connective tissue component, collagen. An important step in the breakdown of glucose to yield energy is catalysis by a multi-enzyme complex called pyruvate dehydrogenase. Pyruvate dehydrogenase is a complex of several enzymes that actually requires one cofactor (a magnesium ion) and five different organic coenzymes to catalyze its specific chemical reaction. Therefore, enzyme function is, in part, regulated by an abundance of various cofactors and coenzymes, which are supplied primarily by the diets of most organisms.

Enzyme Compartmentalization

In eukaryotic cells, molecules such as enzymes are usually compartmentalized into different organelles. This allows for yet another level of regulation of enzyme activity. Enzymes required only for certain cellular processes can be housed separately along with their substrates, allowing for more efficient chemical reactions. Examples of this sort of enzyme regulation based on location and proximity include the enzymes involved in the latter stages of cellular respiration, which take place exclusively in the mitochondria, and the enzymes involved in the digestion of cellular debris and foreign materials, located within lysosomes.

Feedback Inhibition in Metabolic Pathways

Molecules can regulate enzyme function in many ways. A major question remains, however: What are these molecules and where do they come from? Some are cofactors and coenzymes, ions, and organic molecules, as you’ve learned. What other molecules in the cell provide enzymatic regulation, such as allosteric modulation, and competitive and noncompetitive inhibition? The answer is that a wide variety of molecules can perform these roles. Some of these molecules include pharmaceutical and non-pharmaceutical drugs, toxins, and poisons from the environment. Perhaps the most relevant sources of enzyme regulatory molecules, with respect to cellular metabolism, are the products of the cellular metabolic reactions themselves. In a most efficient and elegant way, cells have evolved to use the products of their own reactions for feedback inhibition of enzyme activity. Feedback inhibition involves the use of a reaction product to regulate its own further production (Figure 6.21). The cell responds to the abundance of specific products by slowing down production during anabolic or catabolic reactions. Such reaction products may inhibit the enzymes that catalyzed their production through the mechanisms described above.

The production of both amino acids and nucleotides is controlled through feedback inhibition. Additionally, ATP is an allosteric regulator of some of the enzymes involved in the catabolic breakdown of sugar, the process that produces ATP. In this way, when ATP is abundant, the cell can prevent its further production. Remember that ATP is an unstable molecule that can spontaneously dissociate into ADP. If too much ATP were present in a cell, much of it would go to waste. On the other hand, ADP serves as a positive allosteric regulator (an allosteric activator) for some of the same enzymes that are inhibited by ATP. Thus, when relative levels of ADP are high compared to ATP, the cell is triggered to produce more ATP through the catabolism of sugar.


1 Introduction

In recent years, powerful bioinformatics tools are being increasingly integrated into systems and synthetic biology pipelines ( Carbonell et al., 2016). Synthetic biology employs the engineering principle of an iterative Design–Build–Test–Learn cycle. In the case of developing engineered organisms for the production of high-value compounds, the Design stage involves the identification of the most suitable combinations of starting substrates, enzymes, regulatory components and chassis organism for the desired biosynthetic pathway. Hence, bioinformatics tools used at this stage usually carry out database mining in order to search for the best candidate parts and devices. Some of these tools are capable of establishing possible pathways leading to a target compound by using sets of encoded reaction rules, like RDM patterns in PathPred ( Moriya et al., 2010) Bond-Electron matrices in BNICE ( Hadadi et al., 2016) or reaction SMARTS in RetroPath 2.0 ( Delépine et al., 2018). In order to select candidate sequences for enzymes at each step of the identified pathways, several tools provide different solutions, including antiSMASH for biosynthetic gene clusters ( Weber et al., 2015), as well as tools based on reaction homologies like EC-Blast ( Rahman et al., 2014) or machine learning ( Mellor et al., 2016). Here, we extend such capabilities through Selenzyme, sequence selection with the ability to mine SMARTS reaction rules. The tool is part of the SYNBIOCHEM automated Design/Build/Test/Learn pipeline for microbial fine chemical production, which integrates computational, robotics, assembly, analytics and machine learning platforms. Selenzyme is fed from the output of the pathway discovery workflow RetroPath 2.0 ( Delépine et al., 2018) and will be integrated with the downstream tool for part optimization PartsGenie ( Swainston et al., 2017b).


The Chemistry of Protein Catalysis

We report, for the first time, on the statistics of chemical mechanisms and amino acid residue functions that occur in enzyme reaction sequences using the MACiE database of 202 distinct enzyme reaction mechanisms as a knowledge base. MACiE currently holds representatives from each Enzyme Commission sub-subclass where there is an available crystal structure and sufficient evidence in the primary literature for a mechanism. Each catalytic step of every reaction sequence in MACiE is fully annotated, so that it includes the function of the catalytic residues involved in the reaction and the chemical mechanisms by which substrates are transformed into products. We show that the most catalytic amino acid residues are histidine, cysteine and aspartate, which are also the residues whose side-chains are more likely to serve as reactants, and that have the greatest versatility of function. We show that electrophilic reactions in enzymes are very rare, and the majority of enzyme reactions rely upon nucleophilic and general acid/base chemistry. However, although rare, radical (homolytic) reactions are much more common than electrophilic reactions. Thus, the majority of amino acid residues perform stabilisation roles (as spectators) or proton shuttling roles (as reactants). The analysis presented provides a better understanding of the mechanisms of enzyme catalysis and may act as an initial step in the validation and prediction of mechanism in an enzyme active site.


6.6: Glyoxylate Pathway

  • Contributed by Kevin Ahern & Indira Rajagopal
  • Professor (Biochemistry and Biophysics) at Oregon State University

Succinate continues through the remaining reactions of the CAC to produce oxaloacetate. Glyoxylate combines with another acetyl-CoA (one acetyl-CoA was used to start the cycle) to create malate (catalyzed by malate synthase). Malate can, in turn, be oxidized to oxaloacetate.

It is at this point that the pathway&rsquos contrast with the CAC is apparent. After one turn of the CAC, a single oxaloacetate is produced and it balances the single one used in the first reaction of the cycle. Thus, in the CAC, no net production of oxaloacetate is realized. By contrast, at the end of a turn of the glyoxylate cycle, two oxaloacetates are produced, starting with one. The extra oxaloacetate can then be used to make other molecules, including glucose in gluconeogenesis.

Because animals do not run the glyoxylate cycle, they cannot produce glucose from acetyl-CoA in net amounts, but plants and bacteria can. As a result, these organisms can turn acetyl-CoA from fat into glucose, while animals can&rsquot. Bypassing the decarboxylations (and substrate level phosphorylation) has its costs, however. Each turn of the glyoxylate cycle produces one FADH and one NADH instead of the three NADHs, one ( ext_2), and one GTP made in each turn of the CAC.


Catalysts for a green industry

The chemical industry has always exploited catalysts to do reactions as near to ambient temperature as is practical, thus keeping energy usage and costs down. Today industry faces additional pressure to be cleaner and greener, which will require the development of new catalysts.

The focus of catalyst research is now on finding catalysts that will enable industrial processes to be less polluting, operate with better atom economy, produce purer products and last longer. Although we may think of the catalyst as lasting for ever, this is never the case - all industrial catalysts have a finite lifetime, which makes the search for longer lasting catalysts high on industry's list of priorities.

How catalysts work

In general catalysts are described as substances capable of speeding up a chemical reaction, but there are some reactions that do not proceed at all unless a catalyst is present. These reactions may be thermodynamically feasible but their kinetics are so unfavourable that no reaction occurs.

For chemical reactions to take place the reactant molecules must collide with sufficient energy, the activation energy, to form the activated or transition state complex. Once formed, this transition state will either break down into reactants or into products. A catalyst provides an alternative reaction pathway with a lower activation energy than the uncatalysed reaction. The catalysed reaction can involve several intermediates and transition state complexes, quite different from the one-step mechanism for the reaction in the absence of a catalyst (see Fig 1).

Fig 1 Energy profiles of catalysed and non-catalysed reactions

It is important to note that while the catalyst provides an easier path for reactant molecules to form a transition state, the catalyst also provides an easier path for the reverse reaction in which product molecules return via the transition state to reactant molecules. In this way the catalyst speeds up both forward and reverse reactions to the same extent and so the equilibrium constant remains the same as dictated by the thermodynamics.

Many reactions are multi-step processes of which one will be the slow rate-controlling step, and it is this reaction that the catalyst must be active for, ie provide the alternative pathway. Additionally, many reactions are accompanied by the formation of side products, which may be useful but nevertheless need to be separated and therefore add to the costs of the process. Thus industrial chemists are always looking for catalysts that will provide maximum selectivity to ensure the highest purity of product. Two types of catalyst dominate in the chemical industry: heterogeneous and homogeneous catalysts.

Heterogeneous and homogeneous catalysts

Heterogeneous catalysts are solids that catalyse the reactions between liquid or gaseous reactants. (Note that the reaction itself usually occurs at the surface of the catalyst.) The catalytically active solid is typically coated onto a high surface area support to ensure the maximum exposure to the gas or liquid reaction mixture. These catalysts, usually transition metals and their compounds, are used in ca 85 per cent of industrial processes because they are easy to separate from the products at the end of the reaction. Examples include the Haber-Bosch process for the production of NH3, catalytic cracking, and the hydrogenation of vegetable oils.

A heterogeneous catalyst provides a lower energy path via a sequence that involves adsorption of reactant molecules upon an active site in the surface. The molecules become chemisorbed on the active site, their bonds are disrupted and rearrangements take place to form the activated complex desorption then follows to release the product molecule(s) into the gas, or liquid, phase. The active site is once again vacant to repeat the process. Figure 2 shows adsorbed ethene and adsorbed hydrogen upon the active sites of a nickel catalyst. Following adsorption and reaction, the product ethane desorbs back into the gas phase, leaving the active site vacant for the next reactant molecules. This reaction is the basis of the hydrogenation of unsaturated vegetable oils in the manufacture of margarine.

Fig 2 Adsorption and reaction in heterogenous catalysis

Clearly the adsorption is an important step and the precise structure of the surface is vital in providing the active site. Defects in the solid surface will create different types of site, which may have different or no catalytic properties. The active sites are characterised by having a critical geometry associated with the compounds that adsorb onto the catalyst surface. The geometry of an active site may also be determined by the structure of the underlying support. Thus changing the support can have a profound affect upon activity and may even redirect the course of a reaction.

An active site may be made more active by introducing other atoms or compounds. These are known as promoters, which alone are relatively inactive. For example, if a small amount of cobalt is added to the desulfurisation catalyst molybdenum disulfide there is a marked increase in activity. Poisons have the counter effect and build up on the catalyst surface during its life and often mark the end of the catalyst's life. A platinum hydrogenation catalyst, for example, is poisoned by sulfur-containing compounds.

The understanding of surface structure therefore plays a big role in the development of new catalysts and so it is here that much of the research effort is directed. Where only a small amount of a catalyst surface is productive there is clearly scope for improvement.

Several industrial processes use homogeneous catalysts, which are in the same phase (liquid or gas) as the reactants and products. Although more difficult to separate at the end of a reaction, homogeneous catalysts are often more active and selective than heterogeneous catalysts and tend to work at lower temperatures. This is because all the metal ions of a dissolved catalyst are potentially active sites for the reaction, whereas in a solid only those atoms at the surface are accessible to the reactant molecules. Examples include the acid catalysed esterification of carboxylic acids and alcohols and the gas-phase catalysed reaction of ozone destruction in the stratosphere in which chlorine free radicals, from CFCs, act as catalysts for the reaction.

Important catalytic reactions

Today, the industrial world relies upon an enormous number of chemical reactions and an even greater number of catalysts. A selection of important reactions reveals the scope of modern catalysis and demonstrates how crucial it will be for chemists to achieve their environmental objectives.

A sacrifice: worst case catalyst

A sacrificial, or stoichiometric, catalyst is used once and discarded. The amount of waste produced is not insignificant since these catalysts are used in stoichiometric amounts. For example, the catalyst may typically be in a 1:1 mole ratio with the main reactant.

In the manufacture of anthraquinone for the dyestuffs industry, for example, aluminium chloride is the sacrificial catalyst in the initial step, the acylation of benzene, see equation (i). This is a type of Friedel-Crafts reaction 1 in which the spent catalyst is discarded along with waste from the process. Fresh catalyst is required for the next batch of reactants. The problem is that the aluminium chloride complexes strongly with the products, ie Cl - , forming [AlCl4] - and cannot be economically recycled, resulting in large quantities of corrosive waste.

New catalysts, with better environmental credentials, are now being tried out. Compounds, such as the highly acidic dysprosium(III) triflate (trifluoromethane sulfonate, 1) offer the possibility of breaking away from the sacrificial catalyst by enabling the catalyst to be recycled.

Low sulfur fuels: desulfurisation catalysis

Petroleum-derived fuels contain a small amount of sulfur. Unless removed this sulfur persists throughout the refining processes and ends up in the petrol or diesel. Pressure to reduce atmospheric sulfur has driven the development of catalytic desulfurisation. One of the problems was that much of the sulfur present was in compounds such as the thiophenes, which are stable and resistant to breakdown.

Scheme 1 Desulfurisation of thiophenic compounds from petroleum

The catalyst molybdenum disulfide coated on an alumina support provided one solution. Cobalt is added as a promoter, suggesting that the active site is a molybdenum-cobalt sulfide arrangement. In the catalytic reaction (see Scheme 1), which is essentially a hydrogenation sequence, the adsorbed thiophene molecule is hydrogenated and its aromatic stability destroyed. This enables the C-S bond to break and release the sulfur as hydrogen sulfide. This is an interesting example of a catalyst performing different types of reactions: hydrogenation, elimination and isomerisation.

Current research in this area is directed at increasing catalyst life and improving activity.

Fuel cells: electrocatalysis

In theory, the fuel cell is promising in terms of efficient electricity generation - chemical energy in the fuel is converted directly into electrical energy. Unlike other methods of generating electricity from fuels there is no intermediate thermal stage with attendant energy losses. In practice, however, there is a significant amount of energy consumed in the ancillary equipment, limiting its efficiency.

Like other electrochemical cells, 2 the fuel cell is a redox system. The hydrogen fuel cell, for example, comprises an anode catalyst and cathode catalyst separated by a proton exchange membrane. The latter is a polymer that behaves as an electrolyte and allows protons to pass through. Overall the reaction is the oxidation of hydrogen to form water, which takes place in stages: at the anode, hydrogen is oxidised to give electrons and protons. The electrons pass to the external circuit and the protons pass through the proton exchange membrane to the cathode. At the cathode oxygen from the air reacts with the protons emerging from the membrane and simultaneously takes electrons arriving from the external circuit.

The electrode catalysts are platinum, which is expensive and so research is aimed at finding alternatives. Of the metals being tested an alloy of copper and platinum is showing promise. 3 The platinum is alloyed with copper followed by de-alloying of the surface, leaving a modified platinum surface with improved activity.

Left-handed catalysts: pharmaceuticals

In many therapeutic drugs the active component is a single enantiomer. Generally, chemical reactions give enantiomeric mixtures as the product. Subsequent purification, for example, by fractional crystallisation, to isolate the active enantiomer is an extra process that adds to production costs.

By using chiral catalysts - or asymmetric catalysts - the single active enantiomer can be produced. William Knowles in the 1970s found that rhodium bonded to chiral phosphine ligands (2) could perform asymmetric catalytic hydrogenation. The method was soon developed for the commercial production of the anti-Parkinson drug, l-dopa (Scheme 2). In 2001 Knowles shared the Noble Prize in chemistry with Ryoji Noyori and K. Barry Sharpless for their research on asymmetric catalysis. Today, with the huge expansion of the pharmaceutical industry, there is demand for chiral compounds and other chiral catalysts are now being developed. 4

Scheme 2 Asymmetric hydrogenation of carbon-carbon double bond

Costs less, wastes less: ethanoic acid catalyst

Ethanoic acid is an important industrial chemical with an annual world demand of about six million tonnes. It is used in the synthesis of polyethylene terephthalate (PET), which is used for soft drinks bottles, in the production of photographic film and in the synthesis of synthetic fibres and fabrics, for example. There have been several methods used in its production, including the distillation of soured wine in which the ethanol was oxidised by bacteria to form ethanoic acid. This method, however, could not supply the needs of industry and so synthetic methods were developed. Today, the carbonylation of methanol, which uses a rhodium compound as a homogeneous catalyst, is the major production method. One of the problems with this reaction is that the selectivity is compromised by a side reaction in which propanoic acid is formed. In 1996 BP Chemicals introduced a catalyst - the Cativa catalyst (3) - based upon iridium in place of rhodium. 5

Scheme 3 Carbonylation of methanol using Cativa catalyst

Scheme 3 shows the reaction sequence. This homogeneous catalyst, when combined with a small amount of ruthenium as a promoter, shows higher activity and suffers less from the propanoic acid side reaction, leading to lower costs and less waste. Furthermore, the iridium catalyst is cheaper than the rhodium catalyst.

Conclusion

Catalysis has come a long way and has served industry well in enabling many reactions to be done which, otherwise, would have been uneconomic or even impossible. Today chemists are faced with new challenges as concerns for the environment and scarcity of resources motivates them to look for greener processes.

Tony Hargreaves is a science writer and part-time lecturer in applied chemistry at Calderdale College of Further Education, Halifax.


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Without enzyme catalyst, slowest known biological reaction takes 1 trillion years

One scientist who studies these issues is Dr. Richard Wolfenden, Alumni distinguished professor of biochemistry and biophysics and chemistry at the University of North Carolina at Chapel Hill and a member of the National Academy of Sciences. In 1998, he reported a biological transformation deemed "absolutely essential" in creating the building blocks of DNA and RNA would take 78 million years in water.

"Now we've found one that's 10,000 times slower than that," Wolfenden said. "Its half-time - the time it takes for half the substance to be consumed - is 1 trillion years, 100 times longer than the lifetime of the universe. Enzymes can make this reaction happen in 10 milliseconds."

Wolfenden, along with co-authors Chetan Lad and Nicholas H. Williams of Sheffield University in England, published a report of their new findings April 29 in the online "early edition" of the Proceedings of the National Academy of Sciences. Print publication is slated for May 13.

The report highlights the catalytic power of phosphatase enzymes to tremendously enhance the transformation rate in water of a specific group of biochemicals: phosphate monoesters. Protein phosphatase enzymes acting on these monoesters help regulate the molecular cross-talk within human cells, the cell signaling pathways and biochemical switches involved in health and disease.

"We have esters floating around in our cells with all kinds of functions," Wolfenden said. "Every aspect of cell signaling follows the action of the type of phosphatase enzyme that breaks down phosphate monoesters. Other phosphatases highlighted in the study for their catalytic power help mobilize carbohydrates from animal starch and play a role in transmission of hormonal signals."

As to the uncatalyzed phosphate monoester reaction of 1 trillion years, "This number puts us way beyond the known universe in terms of slowness," he said. "(The enzyme reaction) is 21 orders of magnitude faster than the uncatalyzed case. And the largest we knew about previously was 18. We've approached scales than nobody can grasp."

Why would we want to know the rate of a biological reaction in the absence of an enzyme?

That information would allow biologists to appreciate what natural selection has accomplished over the millennia in the evolution of enzymes as prolific catalysts, Wolfenden said. It also would enable scientists to compare enzymes with artificial catalysts produced in the laboratory.

"Without catalysts, there would be no life at all, from microbes to humans," he said. "It makes you wonder how natural selection operated in such a way as to produce a protein that got off the ground as a primitive catalyst for such an extraordinarily slow reaction." Experimental methods used to observe very slow reactions can generate important information for drug design.

"Enzymes that do a prodigious job of catalysis are, hands-down, the most sensitive targets for drug development," Wolfenden said.

"The enzymes we studied in this report are fascinating because they exceed all other known enzymes in their power as catalysts. We've only begun to understand how to speed up reactions with chemical catalysts, and no one has even come within shouting distance of producing their catalytic power."

Wolfenden's research on enzyme mechanisms and water affinities of biological compounds has exerted major influences in these areas. His research also has influenced rational drug design findings from his laboratory helped spur development of ACE inhibitor drugs, now widely used to treat hypertension and stroke.

Support for this research came from the National Institute of General Medicine, a component of the National Institutes of Health.

Note: Contact Wolfenden at 919-966-1203 or [email protected]
School of Medicine contact: Les Lang, 919-843-9687 or [email protected]

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Watch the video: A-Level Biology - Investigate the progress of enzyme-catalysed reactions (January 2022).