Biochemistry Sheet 29 PDF

29 Ruba Shkokani Celina alsalim Nafez Abutarboush NAMING OF ENZYMES - In general, enzymes end with the suffix (-ase). -Most enzymes are named for their substrates and for the type of reactions they catalyze, with the suffix “ase” added. - The most common way to name an enzyme: first part of the n...

29 Ruba Shkokani Celina alsalim Nafez Abutarboush NAMING OF ENZYMES - In general, enzymes end with the suffix (-ase). -Most enzymes are named for their substrates and for the type of reactions they catalyze, with the suffix “ase” added. - The most common way to name an enzyme: first part of the name is the substrate that binds to the enzyme, the second part is the enzyme’s function, then the suffix -ase-. - For example; ATPase is an enzyme that breaks down ATP, whereas ATP synthase is an enzyme that synthesizes ATP. - Some enzymes aren’t named by the substrate, instead it’s named by its product and therefore you can understand the function of it. - Some enzymes have common names that provide little information about the reactions that they catalyze. - Examples include the proteolytic enzyme trypsin. Historically there were some enzymes named other names where their name doesn’t have anything that indicates it’s an enzyme; however, these names didn’t change and are still there, examples: - Trypsin, found in the small intestine. - Pepsin, found in the stomach. ❖ EC NUMBERNIG (ENZYME COMMISSION NUMBER): - It’s a scientific way to name an enzyme. - A numerical classification scheme for enzymes, based on the chemical reactions they catalyze. - Strictly speaking, EC numbers do not specify enzymes, but enzyme-catalyzed reactions. - Numbering format: - EC followed by four numbers separated by periods. - Major class (1-7), Minor class, subclass, further sub-classification. - Therefore, every enzyme has 4 digits, and those digits specify the enzyme (we have to know only the 7 major classes, accordingly, know which major class any enzyme belongs to). - For example: tripeptide aminopeptidases "EC 3.4.11.4" - EC 3: hydrolases - EC 3.4: hydrolases that act on peptide bonds - EC 3.4.11: hydrolases that cleave off the amino-terminal of the amino acid polypeptide. - EC 3.4.11.4: cleave off the amino-terminal end from a tripeptide Enzymes are classified in two main ways: 1. STRUCTURE AND ARE CLASSIFIED INTO: - Simple enzymes: Which consist of only proteins. - Complex (conjugated) enzymes: Where a functional non-protein structure (ex. Lipids, carbs, phosphate group, etc...) bound to an enzyme. Also called holoenzyme. - Apoenzyme: An enzyme that is not bound to any functional group. - Holoenzyme: a conjugated enzyme (bound to a functional group). - Coenzyme: a non-protein functional group that binds to an enzyme to activate it. 2. FUNCTION are classified into the 7 major classes that we have to know. 1. oxido-reductases: removal of O, O2, H. Require coenzymes (ex. heme) - These enzymes catalyze oxidation & reduction reactions involving the transfer of hydrogen atoms, electrons or oxygen. - There cannot be oxidizing without reduction, by default there must be two reactants and two products, where one will be oxidized and the other will be reduced in the reactants and the same will happen in the products. - This group can be further divided into 4 main classes: A. DEHYDROGENASIS: It catalyzes the hydrogen transfer from the substrate to a molecule known as nicotinamide adenine dinucleotide (NAD+), so NAD+ is the most common recipient of hydrogen (will be reduced) unless otherwise specified. Examples: -Lactate dehydrogenase -Alcohol dehydrogenase B. OXIDASES: Catalyzes the hydrogen transfer from the substrate (therefore oxidizing it) to molecular oxygen O2 (reduced) producing hydrogen peroxide H2O2 as a byproduct. **keep in mind that the oxidized substance is the reducing agent, and the reduced substance is the oxidizing agent. -even though hydrogen peroxide is toxic, it is synthesized in our body, but peroxidases break it down. Examples: -Glucose oxidase C. PEROXIDASES: -Catalyzes the oxidation of a substrate by hydrogen peroxide (oxidizing agent, will be reduced) and the product is water. Example: -Oxidation of two molecules of glutathione (GSH) in the presence of hydrogen peroxide D. OXYGENASES - Oxygenases catalyze substrate oxidation by molecular oxygen (O2) (we are not dealing with oxygen here). - The reduced product of the reaction in this case is water and not hydrogen peroxide. - There are two types of oxygenases: • Monooxygenases: transfer one oxygen atom to the substrate and reduce the other oxygen atom to water. • Dioxygenases: incorporate both atoms of molecular oxygen (O2) into the product(s) of the reaction. Example: -Heme oxygenase 2.Transferases: Transfer of a group from one molecule to another - These enzymes transfer a functional group (C, N, P or S) from one substrate to an acceptor molecule. - The common minor classes of transferases are: A. Kinases These enzymes catalyze the transfer of phosphate group. - Most common doner for phosphate group is ATP, where it donates a phosphate group and gives energy, the high energy bonds that the phosphate group makes with other molecules releases energy when breaking it down, that’s why ATP is an excellent energy storage molecule. Example B. Aminotransferases (Transaminases) - As the name implies it catalyze the transfer of amine group (from amino acids) from one amino acid to a keto acid, converting the amino acid to a keto acid and the keto acid to an amino acid, which allows the interconversion of certain amino acids. - Considered as important enzymes because the only source of nitrogen in our body is the amine group. Look at the following reaction that shows how amine group transfer: - When removing an amine group from an amino acid, a carbonyl group will form, and that leads to the formation of keto acid. - We have to know 3 amino acids and their corresponding keto acid: • Aspartic acid (amino acid) Oxaloacetate (keto acid) • Glutamic acid (amino acid) α-ketoglutaric acid (keto acid) • Alanine (amino acid) Pyruvic acid (keto acid) - Pyruvic acid = pyruvate (remember: the suffix -ate- indicates an acid) which comes from the breaking down of glucose. 3. Hydrolases: addition of water (carbs. & proteins) Hydro= water lases=breakdown - As the name indicates these enzymes catalyze the breakdown of its substrate by adding water. - The substrates that these enzymes breakdown were formed by condensation reaction, which are all the macromolecules in our body (lipids, carbs, nucleic acids). - Peptidases, esterases, lipases, glycosidases, phosphatases, nucleasis are all examples of hydrolases named depending on the type of bond cleaved. Example: • Proteases - one type of hydrolysis. - These enzymes catalyze proteolysis, the hydrolysis of a peptide bond within proteins. - Proteolytic enzymes differ in their degree of substrate specificity. - Trypsin, is quite specific; catalyzes the splitting of peptide bonds only on the carboxyl side of lysine and arginine. - Thrombin catalyzes the hydrolysis of Arg-Gly bonds in particular peptide sequences only. 4. lyases: addition of a molecule (H2O, CO2 , NH3 ) to a double bond or reverse - Catalyze the addition or removal of a functional group from their substrate with the associated formation or removal of double bonds between C-C, C-O, and C-N - As you see in this reaction the addition of water didn’t result in breaking down of the substrate instead it removed the double bond Examples: - Aldolase; breaks down fructose-1,6-biphosphate into dihydroxyacetone phosphate and glyceraldehydes-3-phosphate, as you see in the reaction below - Enolase; interconverts phosphoenolpyruvate and 2-phosphoglycerate by formation and removal of double bonds 5. Isomerases: one substrate and one product - Catalyze intramolecular rearrangements therefore, the conversion of one isomer to another. Examples: - Glucose-6-phosphate isomerase; isomerizes glucose-6-phosphate to fructose-6- phosphate. - Phosphoglycerate mutase; transfers a phosphate group from carbon number 3 to carbon number 2 of phosphorylated glycerate (BPG intermediate). 6. Ligases: usually not favorable, so they require a simultaneous hydrolysis reaction - Catalyzes the building up of materials usually by increasing the number of carbons, this process needs energy so usually you’ll see ATP in these reactions. - Ligases join C-C, C-O, C-N, C-S and C-halogen bonds. - The reaction is usually accompanied by the consumption of a high energy compound such as ATP. Example: -Pyruvate carboxylase 7. Translocases: - Catalyzes the translocation of materials from one place to another. Example: - the translocation of ATP & ADP in the mitochondria ❖CATALYSIS (speeding of reactions) Not all enzymes rely on their active site for catalysis, some enzymes, for example: conjugated enzymes, need a substance other than amino acids to do their function. Conjugated enzymes, as we said before, need to bind to coenzyme that are usually organic in their nature or metallic or organometallic. A. Functional Groups on Amino Acid Side Chains:  Are almost all polar amino acids (nucleophilic catalysis).  Ser, Cys, Lys, & His can participate in covalent catalysis. Histidine: is the most important and common in the enzyme active site amino acid because the pKa of its side chain is very close to the physiological pH & its acid-base catalysis. B. Coenzymes in Catalysis  Usually (but not always) synthesized from vitamins. - Vitamins: are organic structures that cannot be synthesized in our body, and are needed in high amounts because they synthesize enzymes. - Vitamins are species specific, material specific, and condition specific. - 13 Vitamins is discovered till now: - 9 are water soluble (synthesizes coenzymes), which are: B1, B2, B3, B5, B6, B7, B9, B12, and C. - 4 are fat soluble (doesn’t synthesize coenzymes), which are: A, D, E, K. Each coenzyme is specific to a type of reaction. They are either: * Activation-transfer coenzymes: aid the catalysis of formation of covalent bond and breaking it down during a reaction. * Oxidation–reduction coenzymes: Help in the loss or gain of electrons in redox reactions. ❖ ENZYMES COFACTORS - Apoenzyme: An enzyme that is not bound to any functional group. - Holoenzyme: a conjugated enzyme (bound to a functional group). - Prosthetic groups: tightly bound. - Co-substrates: loosely bound. ENZYMES COFACTORS ORGANIC METAL ORGANOMETALLIC PROTEIN-DERIVED HEME STABLE CROSS-LINKED AMINO ACID QUINONE FREE RADICALS TPQ LTQ S TTQ CTQ ❖ACTIVATION-TRANSFER COENZYME - Usually participate directly in catalysis by forming a covalent bond. - Characteristics: Two groups in the coenzyme: ▪ Forms a covalent bond (functional group). ▪ Binds tightly to the enzyme (binding group). Dependence on the enzyme for additional specificity of substrate & additional catalytic power. THE END OF SHEET 29