Enzymes Lecture 6 PDF

Enzymes LECTURE 6 Enzymes Proteins that __________ the biochemical reactions Large molecules that __________ of chemical reactions without themselves undergoing any change Mostly occur as globular proteins or ribozymes Characteristics: They are extremely __________, increasing re...

Enzymes LECTURE 6 Enzymes Proteins that __________ the biochemical reactions Large molecules that __________ of chemical reactions without themselves undergoing any change Mostly occur as globular proteins or ribozymes Characteristics: They are extremely __________, increasing reaction rates by anywhere from 109 to 1020 times. Most of them are extremely __________.  Classifications of Enzymes Oxidoreductases Transferases Isomerases Hydrolases Lyases Ligases  Classifications of Enzymes __________ Catalyze oxidation and reduction Classifications of Enzymes __________ Catalyze the transfer of a group of atoms, such as from one molecule to another Phosphoryl group  Classifications of Enzymes __________ Catalyze hydrolysis Classifications of Enzymes __________ Catalyze the addition of a group to a double bond or the removal of a group from adjacent atoms to create a double bond Classifications of Enzymes __________ Catalyze the addition of a group to a double bond or the removal of a group from adjacent atoms to create a double bond Classifications of Enzymes __________ Catalyze the conversion of one isomer into another Classifications of Enzymes __________ Catalyze the joining of two molecules accompanied by ATP-ADP interconversion  Nomenclature of Enzymes Derived from the reaction that they catalyze and/or the compound or type of compound on which they act Lactate dehydrogenase → the removal of hydrogen from lactate Acid phosphatase → the hydrolysis of phosphate ester bonds under acidic conditions Based on old names Pepsin, trypsin, and chymotrypsin: Enzymes of the digestive tract  Nomenclature of Enzymes Exercise: Identify the classification of the enzyme used in each reaction.  Nomenclature of Enzymes Exercise: Identify the classification of the enzyme used in each reaction.  Nomenclature of Enzymes Exercise: Identify the classification of the enzyme used in each reaction.  Nomenclature of Enzymes Exercise: Identify the classification of the enzyme used in each reaction. Effect of Enzymes on Activation Energy of Reaction Enzymes provide a __________ for the conversion of the substrate into the product  Effect of Substrate Concentration on Enzyme- Catalyzed Reaction The formation of an __________ Conversion of substrate into product and release of the product and enzyme Enzyme-Substrate Complex  Mechanisms of Enzyme Action ____________ (Fischer, 1894): The enzyme is a rigid, 3D body. The surface that contains the active site has a restricted and very specific opening into which only one kind of substrate can fit.  Mechanisms of Enzyme Action ____________ (Koshland, 1958): The enzyme is flexible and approximates the shape of the substrate. The active site “molds” itself to accommodate the substrate for it to fit the enzyme and create the E-S complex. Enzyme Specificity Absolute Group Linkage Stereochemical  Enzyme Specificity __________ Examples: Urease Aminoacyl tRNA Catalyze the reaction of only one substrate synthetase Enzyme Specificity __________ Catalyze reactions involving similar molecules hexokinase having the same functional group Examples: Hexokinase Lipase  Enzyme Specificity trypsin trypsin __________ Examples: Proteases (chymotrypsin, Catalyze the formation or breakage of only trypsin, elastase) certain bonds in a molecule Enzyme Specificity Example: Arginase __________ Can distinguish one enantiomer from another Transition State Product Formation  Cofactor __________ : The nonprotein part of an enzyme necessary for its catalytic function __________ : The protein (polypeptide) portion of the enzyme __________ : The compound on which the enzyme works, and whose reaction it speeds up  Coenzyme __________ : Organic molecules that serve as carriers of electrons or chemical groups  Coenzyme ______ : an organic substance that is required in the diet in only small amounts Environmental Effects Temperature __________ : temperature at which the enzyme is functioning optimally and the rate of the reaction is maximal Environmental Effects pH __________ : pH at which the enzyme is functioning optimally Environmental Effects pH Lysosomes Specialized vesicles in the cells that contain ~50 different types of hydrolases to digest large molecules Lysosomal enzymes have pH optimum of 4.8  Enzyme Activity Regulation Allosteric Enzymes Enzymes that have more than a single binding site Regulation takes place by means of an event that occurs at a site other than the active site but eventually affects the active site __________ : alter the shape of the active site of the enzyme  Enzyme Activity Regulation Allosteric Enzymes __________ allosterism: effector binding converts the active site to an inactive configuration. __________ allosterism: effector binding converts the active site to an active configuration  Enzyme Activity Regulation Allosteric Enzymes Negative allosterism: ATP as negative High amount of ATP ATP binds to an effector binding site of allosteric effector molecule phosphofructokinase ↓ enzyme activity Glycolysis slows down  Enzyme Activity Regulation Allosteric Enzymes Positive allosterism: AMP as positive High amount of AMP AMP binds to an effector binding site of allosteric effector molecule (precursor of ATP) phosphofructokinase ↑ enzyme activity Glycolysis speeds up  Enzyme Activity Regulation Binds to an effector Feedback Inhibition ↑ F (product) binding site of E1 as a negative An enzyme regulation process in which effector molecule formation of a product inhibits an earlier reaction in the sequence Active site closes E1 will not bind to substrate A  Enzyme Activity Regulation Feedback Inhibition  Enzyme Activity Regulation Feedback Inhibition ↓ F (product) Dissociates from the effector binding Metabolic on-off switch site of E1 Active site becomes E1 becomes active available and can bind to substrate A  Enzyme Activity Regulation Proenzymes A protein that becomes an active enzyme after undergoing a chemical change  Enzyme Activity Regulation Protein modification Adenosine Adenosine triphosphate diphosphate A change in the primary structure usually by an addition of a functional group Pyruvate kinase covalently bonded to the apoenzyme Pyruvate kinase phosphate Phosphate group  Enzyme Activity Inhibition __________ Inhibitors Bind very tightly to one of the R groups of an amino acid in the active site Effectively eliminates catalysis Examples: Arsenic, snake venom, nerve gases  Enzyme Activity Inhibition __________ Inhibitors __________ inhibitors Temporarily slows down enzyme activity bind to the E-S complex Can be competitive, noncompetitive, or uncompetitive  __________ __________ inhibitors bind to the inhibitors bind to some active site of the other portion of the enzyme surface enzyme surface Enzymes in Medicine Enzyme assays When enzyme activity is higher or lower than normal, there might be an onset or progression of a certain disease in a patient or client Enzymes in Medicine Disease diagnosed Biomarker with increased activity Enzyme assays When enzyme activity is higher or __________ Myoglobin, creatine kinase MB (CKMB), cardiac troponin I lower than normal, there might be an onset or progression of a __________ Amylase, lipase certain disease in a patient or __________ Alanine aminotransferase/serum client glutamate-pyruvate transaminase (ALT/SGPT), aspartate aminotransferase/serum glutamate- oxaloacetate transaminase (AST/SGOT) Enzymes in Medicine Enzymes as analytical reagents In clinical laboratories, __________ is used to analyze urea levels in blood and to diagnose kidney malfunction Enzymes in Medicine Enzyme replacement therapy __________ enzymes are given to patients who underwent __________ operation Cerezyme, a synthetic enzyme made from __________ through recombinant DNA technology, are given to patients with __________