BMS100_2_Reaction types_v1.pptx

What are enzymes, and why do we need them? Enzyme Classifications       EC 1) Oxidoreductases EC 2) Transferases EC 3) Hydrolases EC 4) Lyases EC 5) Isomerases Oxidoreductases  Oxidoreductases catalyze redox reactions  Redox = reduction/oxidation  Why do we care about redox reaction...

What are enzymes, and why do we need them? Enzyme Classifications       EC 1) Oxidoreductases EC 2) Transferases EC 3) Hydrolases EC 4) Lyases EC 5) Isomerases Oxidoreductases  Oxidoreductases catalyze redox reactions  Redox = reduction/oxidation  Why do we care about redox reactions?  Occur in a lot of anabolic (?) and catabolic (?) processes What defines a redox reaction?  How can you tell if a redox reaction has happened?  LEO the lion says GER Loss of Electrons = Oxidation, Gain of E lectrons = Reduction Oxidoreductases  Redox Example: CAC (citric acid cycle) (?)  Diagram Questions: succinate is oxidized to make fumerate  FAD is reduced to make FADH2  What are FAD/FADH ? 2  H H H H FAD binds to enzyme active site Succinate dehydrogenase H H FAD is reduced; gained H Based on: https://commons.wikimedia.org/wiki/File:Cycle_de_Krebs_08.png Oxidoreductases  Redox Example: CAC  Diagram Questions: malate is oxidized to make oxaloacetate  NAD+ is reduced to make NADH  What are NAD+/NADH?  Malate Malate dehydrogenase Oxaloacetate Present in TCA Based on: https://commons.wikimedia.org/wiki/File:Krebs_cycle_8_ l-malate_to_oxaloacetate.svg Oxidoreductases  Specific examples of oxidoreductases include: Dehydrogenases – remove H’s and donate them to a molecule other than oxygen  Oxidases – remove H’s and donate them to oxygen  Oxidoreductases  What type of oxidoreductase is used in these rxns? H H H H H H Transferases  Next enzyme class = Transferases  Transferases synthesize molecules by catalyzing the transfer of a group from one molecule to another - Often use a mechanism called What is a nucleophilic “nucleophilic substitution” substitution?  Nucleophile has extra electrons  Electrophile is electron deficient Nucleophilic Substitution Nucleophile: Atom with lone electron pair Leaving Group: Group that will be substituted for by “A” A: + B-X A-B + X: Electrophile: Electron deficient atom Does this look familiar? See reactions from last day… Practice Electronegative oxygen attracted to slightly positive carbon https://commons.wikimedia.org/wiki/File:Figure_03_01_01.jpg Glycosidic (covalent/strong) linkage What is the nucleophile, electrophile and leaving group in disaccharide formation?  Review: What makes the electrophile “electron deficient”?  Base Base Base Base Phosphodiester linkage Base Base Based on: https://upload.wikimedia.org/wikipedia/commons/9/95/DNA_synthesis_PL.png What is the nucleophile, electrophile and leaving group in DNA formation?  Review: What makes the electrophile “electron deficient”?  Storage form of FAs Most positive More favoured direction 3x Glycosidic (covalent/strong) linkage Based on: https://commons.wikimedia.org/wiki/File:220_Triglycerides-01.jpg  Which arrow correctly identifies the nucleophile and electrophile in the formation of triglycerides?  The nucleophile in peptide bond formation is different than in the previous examples – which atom is the nucleophile? Carbon is slightly positive; Based on: https://freesvg.org/peptidformationball nucleophile  What is the leaving group in  Nitrogen this is slightly reaction? What name could you give to this reaction based on this? negative; electrophile  At home review: Are any of the previous  Transferases  Specific transferases include:  Kinases   Transfer a phosphate group from ATP to another (non-water) molecule Polymerases  Transfers a monomer to a polymer, especially wrt DNA and RNA ATP ADP Glucose  Glucose-6-phosphate Glucose-6-kinase Unidirectional reaction w kinase enzyme Transferases  Specific transferases continued:  “X” transferases  Transfer “X” from one molecule to another  “X” = name of group being transferred, with the ending changed to “yl”  Example: if “X”= a peptide, then the enzyme is a peptidyl transferase  xample: if “X”= a fatty acid, then the enzyme is an acyl transferase Transferases  Determine the type of transferase + ATP Do you know which important metabolic pathway this reaction belongs to? + ADP https://commons.wikimedia.org/wiki/File:Gl%C3%BCk%C3%B3z-6-foszfat%C3%A1z.png https://commons.wikimedia.org/wiki/File:ATP_chemical_structure.png  Sometimes, enzymes names are not what you would expect  Could be named for the reverse reaction FAIRLY HIGH ENERGY, NEEDS TO BE RELEASED http://www.natuurlijkerwijs.com/english/citroenzuurcyclus.htm UNIDIRECTIONAL FYI: This a reaction in the breakdown of glucose for energy (glycolysis) Based on: Transferases  Note that many transfer reactions require the use of a “carrier”  Added to the transfer molecule in place of a functional group  Better leaving group than the functional group it replaces Transferases  CoASH (?) is the “carrier” that replaces the OH on fatty acids during TG formation CoAS CoAS CoAS - A fatty acid attached to CoASH is called a “fatty acyl” - What type of 3 CoASH Transferases  The transfer of monosaccharides also uses carriers 3 1 UDP 2 - + UDP Based on: https://commons.wikimedia.org/wiki/File:Figure_03_01_01.jp https://commons.wikimedia.org/wiki/File:SPS_Mechanism.png - What type of biomolecule is UDP? Nucleotide Why is UDP a better leaving group than OH? (due to phosphates that are present) What type of transferase enzyme is being used? (transferring glucose; Hydrolases  Next enzyme class = hydrolases  Hydrolases catalyze hydrolysis reactions  Specific hydrolyases include:  Phosphatases  Hydrolyse monophosphate esters (ex AMP, but not ATP) to release a phosphate group AMP: adenosine monophosphate ATP: adenosine triphosphate https://commons.wikimedia.org/ wiki/ File:DAMP_chemical_structure.svg https://commons.wikimedia.org/wiki/ File:ATP_chemical_structure.png Hydrolases  Specific hydrolases continued:  ATPases   Hydrolyse ATP to release a phosphate group “X”-ases, where “X” refers to the molecule being broken apart  Ex Peptidases hydrolyse peptides to release smaller fragments In each case, water is acting as a nucleophile to break apart a molecule, so the mechanism is Hydrolases   What molecule is acting as a nucleophile in each reaction? Relate this to the reaction name. What type of hydrolase enzyme is being used by each reaction? + + + ATP https://commons.wikimedia.org/wiki/File:Glycolysis_pathway_2.png https://commons.wikimedia.org/wiki/File:H2O_Lewis_Structure_PNG.png + ADP https://en.wikipedia.org/wiki/Adenosine_diphosphate Hydrolases What are the molecules involved?  What type of reaction is depicted?  What is the enzyme class?  What is the specific  Di-acyl-glycerol OH https://commons.wikimedia.org/wiki/File:Lipid_hydrolys Hydrolases What are the molecules involved?  What type of reaction is depicted?  What is the enzyme class?  What is the specific enzyme?  Glycosidic linkage https://commons.wikimedia.org/wiki/File:Amylase_hydrolysisl_1-4 Hydrolases What are the molecules involved?  What type of reaction is depicted?  What is the enzyme class?  What is the Can you figure out what specific same physiological enzyme? process uses these last 3  https://commons.wikimedia.org/wiki/File:Peptide_bond_cleavage.s Lyases  Next enzyme class = lyases  Three types of reactions catalyzed by lyases include:  1) Addition   Adds one molecule to another, commonly across a 2X (or 3X) carbon bond Type of lysase = hydratase  What molecule is added?  Water is added to the molecule (NOT breaking a bond with other enzymes) FYI: This a reaction in the breakdown of fatty acids for energy (beta oxidati https://commons.wikimedia.org/wiki/File:Enoyl-CoA_hydratase_reaction_cis.svg Lyases  2) Elimination   Removes atoms in a molecule to create a double bond Types of lyases:  Dehydratases: What is removed?  Water  Decarboxylases: What is removed?  Carboxyl FYI: This a reaction in the synthesis of fatty acids http://www.lookfordiagnosis.com/images.php?term=https:// commons.wikimedia.org/wiki/File:3-hydroxyacylACP_dehydrase_reaction.svgEnoylCoa+Hydratase&lang=1&from=8 https://commons.wikimedia.org/wiki/File:L-DOPA-to-dopamine.svg FYI: Synthesis of dopamine Lyases  3) Condensation   Joins two molecules, creating a new C-C bond Type of lyase = synthase Porphobilinogen Synthase 2 New C-C bond FYI: This a reaction in the synthesis of heme https://commons.wikimedia.org/wiki/File:Heme-Synthesis-Chemical-Details-Mirror.svg  Sometimes, enzymes names are not what you would expect  Could be that a common name is more widely used than the EC name fumerase http://www.natuurlijkerwijs.com/english/citroenzuurcyclus.htm This reaction is part of the CAC +H2O Fumarate  Malate What type of lyase enzyme do you think is being used? Dohttps://commons.wikimedia.org/wiki/ you know this enzyme File:Malate_Dehydrogenase_Catalyzed_Reaction_of_L- https://commons.wikimedia.org/wiki/ File:Tenofovir_disoproxil_fumarate.svg Post learning  At home terminology review differentiate the following terms: Hydration, hydrolysis, hydratase, hydrolase  Dehydration, dehydratase, dehydrogenase  Isomerases  Next enzyme class = isomerases Isomerization = rearrangement of group(s) within a molecule: No net addition or elimination of atoms  Specific isomerases include:   Mutases:   Epimerases:   Transfer functional groups intramolecularly Interconvert the groups around an asymmetric carbon (?) in a molecule that has more than one asymmetric carbon Racemases:  Interconvert the groups around an asymmetric carbon in a molecule that only has one asymmetric Isomerases  Name the type of isomerase for each reaction http://www.sparknotes.com/biology/cellrespiration/glycolysis/section2.rhtml https://commons.wikimedia.org/wiki/File:3PG-2PG.PNG Phosphate moved from 3 position to 2 position https://commons.wikimedia.org/wiki/File:Aspartate_racemase_gene ral_reaction.png http://www.fasebj.org/content/25/2/497/F1.expansion.html https://en.wikipedia.org/wiki/File:Ribulose-phosphate_3-epimerase_ reaction.jpg  Note: a reaction can be an isomerization but not use an enzyme from the isomerase class Example: aconitate hydratase for isomerization of citrate to isocitrate in isomers the CAC  Citrate  Isocitrate The name is based on the last part of the mechanism Citrate Aconitate Isocitrate http://www.humboldt.edu/~rap1/C431.F01/C431Notes/C431n12nov.htm https://commons.wikimedia.org/wiki/File:Citrate-isocitrate_ Ligases  Next enzyme class = ligases Ligases catalyze various reactions that join 2 molecules with the use of ATP for energy  Specific ligases include:   “X”-ligases and “X”-synthetases (sometimes both!)   “X” refers to the name of the molecules being joined, or to the molecule being created FYI: Although “synthases” used to only be considered types of enzymes that joined molecules without the use of ATP, the term “synthase” can now also be synonymously with Ligases  Example: glutamate-cysteine ligase, aka γ-glutamylcysteine synthetase FYI: This is the first step in making glutathione, an important antioxidant in our bodies https://commons.wikimedia.org/wiki/File:Gsh_mitochondria.jpg Overview Enzyme Class Reaction Example Oxidoreduct Redox ase Hydrolase Hydrolysis (nucleophilic sub.) Transferase Group transfer (nucleophilic sub.) Enzyme Name Example(s) Dehydrogenase, Oxidase Phosphatase, ATPase, Peptidase, Lipase, etc Kinase, Polymerase, “X”transferase Lyase Condensation Synthase Lyase Decarboxylation/ elimination Decarboxylase Lyase Dehydration/ elimination Dehydratase Lyase Hydration/addition Hydratase Isomerase Isomerization Mutase, epimerase,