ENZYME PART 3 FLIP BOOK final

ENZYMES PART 3

ENZYMES

OUTLINE 1 Classification of Enzymes 2 Enzymes and Cofactors 3 Enzyme Inhibitors 4 Allosteric Enzymes 5 Isoenzymes and Multienzymes

CLASSIFICATION OF ENZYMES

CLASSIFICATION OF ENZYMES Have 6 categories Each enzyme has an official Number consists in 4 international name ending with – digits (referred to a class ase and a classification number and subclass of reaction Table 5.1, pg. 136 Boyer, R., Concepts in Biochemistry, 3rd Ed., 2006, John Wiley &Sons

CLASSIFICATION OF ENZYMES - EXAMPLE Class Example Reaction 1 Alcohol dehydrogenase O (oxidoreductase) CH3CH2OH + NAD+ CH3CH + NADH + H+ Hexokinase 2 Glucose + ATP  GLUCOSE-6- (transferase) Chymotrypsin PHOSPHATE + ATP 3 Polypeptide + H2O  peptides (hydrolase) More examples: Refer Table 5.2, pg 136 , Boyer, R., Concepts in Biochemistry, 3rd Ed., 2006, John Wiley & Sons

CLASSIFICATION OF ENZYMES – EXAMPLE (CONT.) Class Example Reaction 4 Pyruvate (lyase) decarboxylase 5 Alanine D-alanine L-alanine (isomerases) racemase 6 Pyruvate (ligases) carboxylase More examples: Refer Table 5.2, pg 136 , Boyer, R., Concepts in Biochemistry, 3rd Ed., 2006, John Wiley & Sons

ENZYMES AND COFACTORS

Cofactor ENZYMES AND COFACTORS Active site Holoenzyme Coenzyme 0 1 an enzyme in its complete form Holoenzyme including polypeptide(s) and cofactor Apoenzyme (inactive) + cofactor Apoenzyme 0 2 enzyme in its polypeptide form without any necessary prosthetic groups or cofactors holoenzyme (active)

ENZYMES AND COFACTORS Enzymes require chemical entity in order to function properly (assists an enzyme in catalytic action) Cofactor – nonprotein molecule that assist in an enzyme catalytic reaction

ENZYME AND COFACTOR Cofactors are divided into 2 categories: metal ions and coenzymes ENZYME INHIBITORS Coenzyme Cosubstrates Prosthetic group Smaller organic or Weakly bound to enzyme, Coenzymes that are covalently temporarily associated with bound, tightly bound to enzyme organometallic molecule derived enzymes and always present from vitamin Eg. NAD+ , FAD+ Eg. heme in catalase

ENZYME INHIBITORS http://www.wiley.com/college/pratt/0471393878/student/animations/enzyme_inhibition/index.html

ENZYME INHIBITORS 2 types of inhibitors 1 Competitive Inhibitors • Compete with substrates for active site • Occupy the active site so that substrate couldn’t bind there • Inhibition can be overcome by adding substrate molecules to the environment 2 Non-Competitive Inhibitors • Attach to the enzyme in some other places (allosteric site) than the active site • Causes the enzymes active site to change its shape (no longer complementary to substrate) • Enzyme can no longer catalyze the reaction • Inhibition CANNOT be overcome

ALLOSTERIC ENZYMES

ALLOSTERIC ENZYMES Allosteric enzyme: an oligomer whose biological activity is affected by other substances binding to it • these substances change the enzyme’s activity by altering the conformation(s) of its 4°structure Allosteric effector: a substance that modifies the behavior of an allosteric enzyme; may be an: • allosteric inhibitor = negative effectors • allosteric activator = positive effectors

ALLOSTERIC ENZYMES The key to allosteric behavior is the existence of multiple forms for the 4°structure of the enzyme • allosteric effector: a substance that modifies the 4° structure of an allosteric enzyme • homotropic effects: allosteric interactions that occur when several identical molecules are bound to the protein; e.g., the binding of aspartate to ATCase • heterotropic effects: allosteric interactions that occur when different substances are bound to the protein; e.g., inhibition of ATCase by CTP and activation by ATP * ATCase = aspartate transcarbomylase CTP = cytidine triphosphate

ALLOSTERIC ENZYMES • A change in conformational structure at one location of a multisubunit protein that causes a conformational change at another location on the protein • Effectors i. +ve effectors - serves as stimulants to enzyme = increase catalytic activity ii. -ve effectors ( inhibitors) to enzyme = reduce/inhibit catalytic activity • Act by reversible, noncovalent binding to a site on the enzyme • Larger and more complex than non-allosteric enzyme • Have 2 or more subunits (oligomeric) • Allosteric enzymes have regulatory sites for binding of substrates and reaction (catalytic sites)

Figure 6.3a Concepts in Biochemistry, 3/e HOMOTROPHIC ©2006 John Wiley & Sons ALLOSTERIC EXAMPLE • A Tetrameric allosteric enzyme composed of 4 identical subunits • Each subunit has a catalytic site where substrate/effector will bind and transformed to product • Once bound to an active site, a message will be transmitted via conformational changes to an active site on another subunit which makes it easier for a substrate molecule to bind and react at that site • This type (substrate and effector) is the same is called cooperative or homotropic

HETEROTROPHIC ALLOSTERISM EXAMPLE • A dimer with nonidentical subunits • Subunit α contain the active site – catalytic subunit • Subunit β contains the site for effector binding – regulatory subunit • Binding of a specific effector molecule to the regulatory site on the β subunit sends a signal via conformational changes to the catalytic site on subunit α • Substrate and effector different kinds of molecules - heterotropic

ALLOSTERIC ENZYME IN FEEDBACK INHIBITION Formation of product inhibits its continued production – feedback inhibition

ENZYME AND COFACTOR Cofactors are divided into 2 categories: metal ions and coenzymes ISOENZYMES AND MULTIENZYMES Coenzyme Cosubstrates Prosthetic group Smaller organic or Weakly bound to enzyme, Coenzymes that are covalently temporarily associated with bound, tightly bound to enzyme organometallic molecule derived enzymes and always present from vitamin Eg. NAD+ , FAD+ Eg. heme in catalase

ISOENZYMES • Enzymes that catalyze the same reaction (catalytically and structurally similar) but are encoded by different genes • Example: Glycogen phosphorylase - synthesize in liver, brain and muscle - involves in degradation of glycogen • Isoenzymes = isoforms

Substrate MULTIENZYMES Enzyme 1 • A group of noncovalently associated 1 enzymes that catalyze 2 or more sequential steps in metabolic/biochemical pathway Enzyme 2 2 • Example: Glycolysis involve multienzymes Enzyme 3 3 Enzyme 4 4 Enzyme 5 5 Enzyme 6 6 Enzyme 7 7 Final product © Brooks/Cole, Cengage Learning