Enzymes are biological catalysts that speed up chemical processes inside of live cells while undergoing no general change in their own structure. Enzymes also known as biocatalysts. The word 'enzyme' derived from the Greek terms, , which " " means within and " " means yeast. Enzymes can be found in all tissues and fluids of the body. There are 6 main classes of enzymes which are oxidoreductases, transferases, hydrolases, lyases, isomerases and ligases. enzumé en zumé INTRODUCTION characteristics Most of enzymes are proteins Highly specific and only bind to certain substrates for certain reactions 1. 2. Functions Aid in signal transduction E.g.: Protein kinase catalyzes the phosphorylation of proteins. Break down large molecules into smaller substances Body can more readily to absorb. Aid in the body's energy production E.g.: The uses of ATP synthase for synthesis of energy. Perform a variety of biochemical processes Such as hydrolysis, reduction, oxidation and many more to remove unwanted materials from the plasma membrane classification of enzymes Why need to classify? Lack of consistency in the nomenclature Who classifies enzymes? International Union of Biochemistry and Molecular Biology (IUBMB) How to classify? The Enzyme Commision Number is a code number made up of four parts separated by dots was given to each enzyme: Using classification system known as the Enzyme Commission Number Main enzyme classes First digit Second digit Subclass Third digit Sub-subclasses Fourth digit Enzyme serial number in its sub-subclass Figure 1. Adapted from What Is Feedback Inhibition?, by Ashish, 2018, Science ABC (https://www.scienceabc.com/humans/feedback-inhibitionof-enzymes-biology-definition-example.html).
A broad family of enzymes that participate in oxidation and reduction processes by transporting Hydrogen atoms, Oxygen atoms, or electrons from one molecule (donor) to another molecule (acceptor). Oxidoreductases classified as Enzyme Class 1 (EC 1) where the second digit determines Hydrogen and electron donor, and the third digit determines for the acceptor. There are 6 subclasses in this family. Oxidases Oxygen acts as an acceptor of hydrogen or electrons Lactate dehydrogenase catalyzes the oxidation of lactate to pyruvate Figure 2. Adapted from "Measurement of Apoptotic and Necrotic Cell Death in Primary Hepatocyte Cultures," by Maes, M., Vanhaecke, T., Cogliati, B., Yanguas, S. C., Willebrords, J., Rogiers, V., & Vinken, M., 2014, Methods in Molecular Biology, p. 349- 361 (https://doi.org/10.1007/978-1-4939-2074-7_2). Dehydogenases Oxidize a substrate by transferring hydrogen to an acceptor molecule Alcohol dehydrogenase catalyzes the reduction of NAD+ to NADH Figure 3. Adapted from "Alcohol Metabolizing Enzymes, Microsomal Ethanol Oxidizing System, Cytochrome P450 2E1, Catalase, and Aldehyde Dehydrogenase in Alcohol-Associated Liver Disease," by Jiang, Y., Zhang, T., Kusumanchi, P., Han, S., Yang, Z., & Liangpunsakul, S., 2020, Biomedicines, 8(3), p. 50 (https://doi.org/10.3390/biomedicines8030050). oxygenases Incorporate oxygen from O2 into organic substrates Cysteine dioxygenase (CDO) catalyzes the conversion of Lcysteine to cysteine sulfinic acid (cysteine sulfinate) peroxidases Catalyze the reduction of hydrogen peroxide and hydroperoxides Glutathione peroxidase catalyzes the conversion of hydrogen peroxide to water OXIDOREDUCTASES Reductases Catalyze reduction reactions Aldose reductase catalyzes the reduction of glucose to sorbitol This class of enzymes, which are found in the liver, effectively detoxify and eliminate substances from the body. Applications Drug metabolism This class of enzymes are needed during glycolysis, citric acid cycle, oxidative phosphorylation and electron transport chain. Aerobic and anaerobic metabolism hydroxylases Addition of hydroxyl groups to substrates Tryptophan hydroxylases catalyzes tryptophan to form 5-hydroxytryptophan in serotonin synthesis Figure 4. Adapted from The Health Implications of Depression, by Tram, M., 2019, HubPages (https://discover.hubpages.com/health/The-HealthImplications-of-Depression). Figure 5. Adapted from "Review: Taurine: A “very essential” amino acid," by Ripps, H., & Shen, W., 2012, Molecular Vision, 18, p. 2673- 2686 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501277/). Figure 6. Adapted from Cognitive Function In Depth, by Drake, V. J., 2011, Oregon State University (https://lpi.oregonstate.edu/mic/health- disease/cognitive-function). Figure 7. Adapted from "Aldose reductase inhibition improves altered glucose metabolism of isolated diabetic rat hearts," by Trueblood, N., & Ramasamy, R., 1998, American Journal of Physiology-Heart and Circulatory Physiology, 275(1), p. H75-H83 (https://doi.org/10.1152/ajpheart.1998.275.1.h75).
In biochemistry, transferases are enzymes that catalyze the transfer of a group of atoms from a donor substrate to an acceptor molecule, including amine, carboxyl, carbonyl, methyl, acyl, glycosyl, and phosphoryl. Transferases are used during translation as well as a variety of other cellular processes. The EC number categorization for transferases is EC2. Transferases are classified into ten groups based on the type of biochemical group transferred. EC2.1 methyltransferases (single-carbon groups) EC2.6 transaminase (nitrogenous groups) EC2.2 transketolase (aldehyde/ketone groups) EC2.7 polymerase (phosphorus groups) EC2.3 acyltransferase (acyl groups) EC2.8 sulfurtransferase (sulfur groups) EC2.4 glycosyltransferase (glycosyl groups) EC2.9 selenotransferase (selenium groups) EC2.5 riboflavin synthase (alkyl/aryl groups) EC2.10 tungstentransferase (tungsten groups) TRANSFERASES Classification of transferases into subclasses terminal transferases To produce plasmid vectors or DNA labeling by adding deoxynucleotides to the downstream end or 3' end of an existing DNA molecule. glutathione transferases A biosensor to toxins like insecticides and herbicides in plants. Anti-cancer drugs (drug resistance). Help transgenic plants survive biotic and abiotic stress. Rubber transferases Sunflower and tobacco create transgenic versions that can synthesize natural rubber by sequencing the rubber transferase enzyme complex's components. DEFICIENCIES SCOT (leads to a buildup of ketones), CPT-II (leads to an excess long chain of fatty acids), and Galactosemia (inability to process galactose).
A type of hydrolytic enzyme that is often utilized as a biochemical catalyst since it uses water as a hydroxyl group donor during the substrate breakdown reaction. In simple words, a hydrolase is an enzyme that catalyzes the hydrolysis of chemical bonds in biomolecules. Hydrolases are the most numerous and diverse class of enzymes, with over 200 enzymes that catalyze the hydrolysis of various substances. Esterases Esterases Split ester bonds Aspirin (acetylsalicylic acid), for example, is hydrolyzed to salicylate by carboxylesterases in the liver during the first pass classification Based on enzyme commission (EC) Hydrolases belong to enzyme class 3 (EC 3) and are further categorized based on the type of bond they cleave. The four-digit code includes the nature of the bond hydrolyzed, then the nature of the substrate, and lastly the enzyme Based on the active site The active site geometry of different hydrolases is different, in spite of the same catalytic method, i.e., hydrolysis. Thus, a Hierarchical classification of hydrolases Catalytic Sites (HCS) has been proposed which is based on the amino acids involved in catalysis. Split large molecules Hydrolases split large molecules into smaller fragments that can be employed for synthesis, waste excretion, or as carbon sources for energy production. Applications This class of enzymes performs essential degradative processes in the body. Degradative processes HYDROLASES Proteases Hydrolyze peptide bonds of proteins In the small intestine, proteases digest dietary proteins to allow absorption of amino acids glycosidases Degradative intracellular functions Required for the catabolism of polysaccharides, in response to physiological requirements (e.g., glycogen degradation as a source of energy) lipases Hydrolysis of triglycerides Triglycerides are hydrolyzed to diglycerides, monoglycerides, fatty acids and glycerol. Figure 9. Adapted from How enzymes boost cleaning performance.(n.d.).Novozymes. (https://biosolutions.novozymes.com/en/dish/insights/articl e/how-enzymes-boost-cleaning-performance) Figure 10. Adapted from Glycosidase - an overview | ScienceDirect Topics. (n.d.). Www.sciencedirect.com. Retrieved February 10, 2023, from https://www.sciencedirect.com/topics/nursing-andhealth-professions/glycosidase Figure 11. Adapted from Mendes, A. A., Oliveira, P. C., & de Castro, H. F. (2012). Properties and biotechnological applications of porcine pancreatic lipase. Journal of Molecular Catalysis B: Enzymatic, 78, 119–134. https://doi.org/10.1016/j.molcatb.2012.03.004 Figure 8. Adapted from Ester Linkage - an overview | ScienceDirect Topics. (n.d.). Www.sciencedirect.com. https://www.sciencedirect.com/topics/engineering/ester-linkage
An enzymes that removes groups such as ammonia (N-H), carbon dioxide (C-O) and water (O-H) from a substrate to produce double bonds. Lyases classified as Enzyme Class 4 (EC 4) where the second digit indicates the bond broken and the third digit indicates the types of groups removed. Lyases usually have a narrow substrate specificity and do need cofactors to do its function. There are 7 subclasses in this family. LYASES Medical Application When alginate lyase is used in the antibiotic for the treatment of respiratory tract infection, the killing efficiency of the antibiotic is increased. Applications -Alginate lyase Bio-functional Alginate Oligosaccharide The enzyme alginate lyase is used to make alginate oligosaccharide from alginate. Alginate oligosaccharide can be applied in many biological activities such as biotechnology Classification of LYASES into subclasses AND SUB-SUBCLASSES CARBON-CARBON LYASE (4.1) Carboxy-lyase: Decarboxylation of amino acids, beta-keto acids, and alpha-keto acids is catalyzed by this enzyme. Aldehyde-lyase: Catalyze the breakage of carboncarbon bonds in alcohols to form carbanions and aldehydes. Oxo-acid-lyase: Catalyze the cleaves of 3-hydroxy acids. CARBON-OXYGEN LYASE (4.2) Hydro-lyases: Catalyze the C-O bond by elimination of water. Polysaccharide-lyase: Cleave bond in acidic polysaccharide through elimination mechanism and produce unsaturated oligosaccharide molecules as the end product. CARBON-NITROGEN LYASE (4.3) Function: Catalyze the elimination of ammonia and its derivative from substrate. 3 types of lyase: Ammonia-lyase Amidine-lyase Amine-lyase CARBON-SULPHUR LYASE (4.4) Function: Catalyze the release of hydrogen sulfide from the cleavage of the carbon-sulfur bond. CARBON-HALIDE LYASE (4.5) Function: Catalyze the cleavage of a carbonhalogen bond with the elimination of chloride. PHOSPHORUS-OXYGEN LYASE (4.6) Function: Catalyze the cleavage of a phosphorus-oxygen bond. CARBON-PHOSPHORUS LYASE (4.7) Function: cleaving the carbon-phosphorus bond of an alkylphosphonic acid to produce inorganic phosphate (Pi) and a hydrocarbon EXAMPLE: Catalyzes the desulfonation and deamination of L-cysteate, yielding pyruvate, sulfite and ammonium L-cysteate sulfo-lyase Figure 12. Adapted from Sulfonates and Organotrophic Sulfite Metabolism by Cook, A. M., Smits, T. H. M. & Denger, K. , 2008, ResearchGate (https://www.researchgate.net/figure/Some-desulfonationreactions-Methanesulfonate-monooxygenase-is-amulticomponent-system_fig4_30019492). Figure 13. Adapted from Overview on Microbial Enzymatic Production of Algal Oligosaccharides for Nutraceutical Applications by Jagtap, A. & Manohar, C.-S., 2021, ResearchGate (https://www.researchgate.net/figure/Structure-of-alginateand-its-enzymatic-hydrolysis-to-produce-alginateoligosaccharide_fig4_350368246). Alginate Lyase Catalyzes the formation of alginate oligosaccharides from alginate Figure 14. Adapted from Regulation of Nitric Oxide-Sensitive Guanylyl Cyclase by Friebe, A. & Koesling, D., 2003, AHA Journals (https://www.ahajournals.org/doi/10.1161/01.res.0000082524. 34487.31). Guanylate Cyclase Catalyzes the formation of cGMP from GTP. cGMP is second messenger of signaling pathway C-S LYASE (4.4) C-O LYASE (4.2) P-O LYASE (4.6) EXAMPLE: EXAMPLE:
Classification of LYASES into subclasses AND SUB-SUBCLASSES INTRAMOLECULAR LYASE (5.5) ISOMERASE ALTERING MACROMOLECULE CONFORMATION (5.6) INTRAMOLECULAR OXIDOREDUCTASE (5.3) EXAMPLE: Alanine racemase in E. coli catalyzes the conversion of Lalanine to D-alanine. Alanine Racemase ( Act on amino acids) EXAMPLE: Cis-trans Isomerase (5.2) Catalyze maleate to fumarate at 25° and pH 8.4. EXAMPLE: Intramolecular Oxidoreductase (5.3) Catalyze the conversion of dihydroxyacetone phosphate (DHAP) to glyceraldehyde-3- phosphate. An enzymes that catalyze the geometric and structural changes between isomers. Isomerase is classified as Enzyme Class 5 (EC 5) and prevalent in carbohydrate metabolism. There are four mechanisms of isomerase which are ring expansion and contraction via tautomer, epimerization, intramolecular transfer and intramolecular oxidoreduction. The usual form of reaction for isomerase is A-B→ B-A. ISOMERASES RACEMASE & EPIMERASE (5.1) Racemase: Stereochemistry inversion at the target chiral carbon; react on molecule with one chiral carbon. Epimerase: Stereochemistry inversion at the target chiral carbon; react on molecule with multiple chiral carbon but only react with one of them. Further classified into 4 sub-subclasses:- Act on amino acids Act on hydroxy acids Act on carbohydrates Act on other compounds CIS-TRANS ISOMERASE (5.2) Cis-isomers: The geometry rearrangement at the double bonds is catalyzed; Substituents group on the same side. Trans-isomers: The geometry rearrangement at the double bonds is catalyzed: Substituents group on the opposite side. Function: Catalyze the oxidation and reduction reaction that occur between the isomers Further classified into 5 sub-subclasses (depending on their processes):- Interconvert aldoses and ketoses Interconvert keto- and enol-groups Transpose C=C double bonds Transpose S-S bonds Other intramolecular oxidoreductases INTRAMOLECULAR TRANSFERASE (5.4) Function: Facilitate the transfer of functional groups from one region of the molecule to another. Further classified into 5 sub-subclasses (depending on the functional group the enzyme moves):- Transfer acyl groups Phosphotransferases Transfer amino groups Transfer hydroxy groups Transfer other groups Function: Catalyze intramolecular eliminations between isomers. Function: Catalyze changes to the conformation of macromolecules. Racemase & Epimerase (5.1) Figure 15. Adapted from Alanine racemase from ''E. coli'' by Bleckwehl, T., 2013, Registry Of Standard Biological Parts (http://parts.igem.org/Part:BBa_K1172901). Maleate isomerase Figure 16. Adapted from Computational investigations on the catalytic mechanism of maleate isomerase: the role of the active site cysteine residues by Dokainish, H. M., Ion B. F. & Gauld J. W., 2014, Royal Society of Chemistry (https://pubs.rsc.org/en/content/articlelanding/2014/cp/c4cp01 342e/unauth). Triose-phosphate isomerase in glycolysis Figure 17. Adapted from Triosephosphate isomerase by Sharma, R., 2022, Alchetron (https://alchetron.com/Triosephosphate-isomerase). Applications High-Fructose Corn Syrup Enzyme: Xylose Isomerase Function: Catalyze the conversion of glucose to fructose. Fructose is used widely in the food and pharmaceutical industries. Biofuels Enzyme: Xylose Isomerase Function: Catalyze the conversion of xylose to xylulose which then can undergo fermentation to produce ethanol.
LIGASES EC 6.1 - Form carbon-oxygen bonds EC 6.6 - Form nitrogen-metal bonds EC 6.5 - Form phosphoric ester bonds EC 6.3 - Form carbon-nitrogen bonds EC 6.2 - Form carbon-sulfur bonds EC 6.4 - Form carbon-carbon bonds Classification of LIGASES into subclasses Acylating (adding an acyl group) a transfer RNA with the corresponding amino acid Synthesizes acyl-CoA by using energy from the hydrolysis of nucleoside triphosphate (NTP) Contains a single subclass that produces coordination complexes Enzymes that repair broken phosphodiester bonds in nucleic acids Only one subclass that consists of carboxylating enzymes Contains 5 subclasses in which the enzymes form carbon-nitrogen bonds. E.g acid-ammonia ligases DNA LIGASE T4 RNA LIGASE UBIQUITIN LIGASE Capable of catalyzing the joining of a single-strand 5’ phosphoryl end of an RNA to another single-strand 3’ hydroxyl end of RNA Enhances the joining of DNA strands together by forming phosphodiester bond between phosphate and deoxyribose. Plays a role in the ubiquitination of various protein substrates. Ubiquitination is a process where the ubiquitin-protein is attached onto a substrate protein. Succinate-coa LIGASE DEFICIENCY An inherited disease that manifests as weak muscle tone of children in the first few months of life. The disease causes the delay of motor skills development. Toxic buildup of lactic acid in the body (fatal infantile lactic acidosis) may occur in some individuals. The word ligase stems from a the Latin word ‘ligare’, which translates to “to bind”. Hence, in biology, ligase is an enzyme that facilitates the joining or binding of two molecules through the formation of a new chemical bonds between the molecules. Usually accompanied by the hydrolysis of an energy-rich phosphate bond that is the breakdown of adenosine triphosphate (ATP). Another common name would be synthetases: not to be confused with synthases as this belongs to lyase group.
CONCLUSION To summarize, enzymes play a crucial role in the metabolic process in the body. They are catalytic proteins, meaning that they can speed up the rate of reactions without being destroyed in the process. This characteristic allows them to be reused in another process. Enzymes work by lowering the activation energy which is the energy needed to break the chemical bonds between the molecules, hence allowing them to combine with other molecules and form products. Another characteristic of enzymes is that they are incredibly specific. They can only bind to one specific substrate that is required for the reaction. Enzymes are classified into 6 major classes. First is the oxidoreductase, classified as EC 1 which aids in the oxidation and reduction processes in aerobic and anaerobic metabolism and also glycolysis. Next, EC 2 is transferase, which are used in translation by catalysing the transfer of a group of atoms from donors to acceptors. Third is hydrolases classified as EC 3. Hydrolases aids in the reaction between biomolecules by utilizing water to be hydroxyl donors during hydolysis. Classified as EC 4, lyase is an enzyme in which they remove groups from a substrate to give way to produce double bonds. Isomerase, classified as EC 5, aids in the changing of the structural and geometrical aspects of isomers. Last but not least, classified as EC 6, ligases catalyzes the joining of molecules through the formation of new chemical bonds. In short, the 6 classes of enzymes each play a different role in the body. It is our responsibility to maintain the enzymes in our body as they help us in accelerating the reactions in our cells. By practising a balanced diet, and keeping ourselves hydrated could help in maintaining our enzymes.