Medical Biochemistry Lecture Notes: Enzymes PDF

Enzymes For 2nd year medicine Lecture 1 Introduction to Enzymes  Learning Objectives – Identify the importance and definition of enzymes – Recognize the nomenclature, classification and Specificity of enzymes – Define terms used in enzymology  Importance of enzymol...

Enzymes For 2nd year medicine Lecture 1 Introduction to Enzymes  Learning Objectives – Identify the importance and definition of enzymes – Recognize the nomenclature, classification and Specificity of enzymes – Define terms used in enzymology  Importance of enzymology Enzymes are important for: > - histology 1.Diagnosis: ↓ > - physical cause of disease can be due to Mord of an enzyme investigation assay of particular enzymes can provide useful diagnostic information, for example: cardiac and liver enzymes, genetic disorders caused by missing or deficient enzymes. 2.Monitoring prognosis: measuring the level of the enzyme causing disease Once treatment is started, measurement of enzyme levels can be used to follow up and aid in decision making.  Importance of enzymology(cont.,) Enzymes are important for: 3.Treatment: treatment of the disease contains specific enzymes For example: antibacterial drugs that attack bacterial cell wall, and streptokinase which is useful in dissolving blood clots. 4.Study of toxicology: How it works of affects the body Many chemicals have poisonous action due to interference with essential enzyme, for example: Sarin (nerve gas) is acetylcholinesterase inhibitor.  Definition of Enzymes in not decreases the body ① 2 Enzymes are Biological Catalysts that increase the rate of o chemical reactions without being consumed during the reactions they catalyze. 5 je " - 8) Enzymes Permit reactions to “go” at conditions that the body can tolerate Enzymes can process millions of molecules every second Enzymes are very specific (react with one or only a few types of molecules (substrates). SRNA not 100 % (eX : e Almost all enzymes are very large globular proteins. - Some enzymes require a non- protein component to function properly (cofactors)  Differences between enzymes & inorganic catalysts Enzymes Inorganic catalyst Nature Mostly Proteins Usually metals Effect of heat Heat labile Heat stable Molecular weight High low Most reactions Irreversible Reversibility are reversible reactions Specificity Specific Non-specific  Nomenclature of Enzymes Each enzyme is assigned 2 names ending in ase: a) Recommended or common name: ase is attached either to the end of: 1. Substrate: o E.g., Lactase is the enzyme acting on lactose 2. Enzyme action: not in the end of pyruvate * O is the enzyme that E.g., pyruvate decarboxylase removes carboxyl from pyruvate  Nomenclature of Enzymes(cont.,) Each enzyme is assigned 2 names ending in ase: b)Systematic name with an EC number: Official name that defines exactly reaction catalyzed by the enzyme EC number: 4 digits number that indicates the main & class, subclass, subsubclass & serial number of z enzyme in its subsubclass. Example: - Alcohol Dehydrogenase is EC 1.1.1.1 -- - Tripeptide aminopeptidase is EC 3.4.11.4  Alcohol Dehydrogenase is EC 1.1.1.1 – EC 1 - Oxidoreductases – EC 1.1 - Acting on the CH-OH group of donors (acts on primary or secondary alcohols or hemiacetals) – EC 1.1.1 - With NAD+ or NADP+ as acceptor – EC 1.1.1.1 - Alcohol dehydrogenase Subclass subla & [ Tripeptide aminopeptidase is EC 3.4.11.4 – EC 3 - Hydrolases – EC 3.4 - Acting on peptide bonds (peptidases) – EC 3.4.11 - Aminopeptidases (release of the N-terminal residue from a tripeptide) – EC 3.4.11.4 - Tripeptide aminopeptidase  Classification of enzymes 7 Enzymes are classified into =6 major classes based on the type of the reaction, with numerous subgroups: 1. Oxidoreductases (EC 1): – Catalyze oxidation-reduction reactions, – E.g., Oxidases, Oxygenases, Reductases, Peroxidases Dehydrogenases. 2. Transferases (EC 2): % - /s – Catalyze transfer of functional groups - – E.g., Aminotransferases, Kinases, 3. Hydrolases (EC 3): ① – Catalyze breaking of bonds by addition of water – E.g., Esterases, Peptidases, Phosphatases reversible - - reform - Breaks of  Classification of enzymes(cont.,) 4. Lyases (EC 4): reversible – Catalyze breaking of Guo C-O, C-C or C-N bonds. without water – E.g., Decarboxylases, deaminases. 5. Isomerases (EC 5): 55 jis reversible – Catalyze rearrangement of functional groups. - – E.g., Mutases, Epimerases, Racemases. one) I MER (only irrehonsable 6. Ligases (EC 6): b energy is weel – Catalyze formation of bonds to join 2 molecules. – E.g., Synthetases, Carboxylases. membranel Additional information can be obtained from: https://enzyme.expasy.org/enzyme-byclass.html ↳  adding reductt im reduced It H reduced Oxidized oxidized + I Zie Spink - C no ATP ⑭ Blue up Blue a [ ATP using  Enzyme Specificity Absolute specificity: sig – The enzyme will catalyze only one reaction i.e., reacts - only with a single substrate. – The enzyme will act on a particular - called isomer (only work with the D- or L- form) (Stereochemical specificity ) - - - - Relative specificity (low specificity): – The enzyme will act on a particular type of bond regardless of the rest of the molecular structure Group specificity (intermediate specificity) – The enzyme will act only on molecules that have specific functional groups, as amino, phosphate & methyl groups -- -  Substrate Terms used in enzymology Substrate: enzymes & 310 V , · The substance acted upon by the enzyme to form the product Product: The substance that is produced by the action of the enzyme Apoenzyme: The protein part of the enzyme which is - catalytically inactive confactor needs a to be active Holoenzyme: The apoenzyme + the cofactor Protein non-protein  bind to to activate it - apoenzyme (non-protein) metal ?? Vitamen derivatives Protein non non prote ex: NAD ex : FAD meakband Freely dissociates from enzyme covalently non-coverently ·s %0 ~. Cosubstrate C  Cofactors Cofactor is a non-protein compound needed to convert the inactive apoenzyme into the active holoenzymes Cofactor is either: A metal ion like Ca2+, Zn2+, Mg2+ or An organic molecule (often vitamin derivative) called coenzyme  Cofactors (cont.,): Metal ion: may be: Activator ions: loosely bound to the enzyme. Metal ions of metalloenzymes: tightly bound to enzyme. Coenzyme: may be: Co-substrates: Loosely bound to the enzyme, So, it freely dissociates from enzyme. E.g., NAD. Prosthetic group: Tightly bound, covalently or non-covalently, to the apoenzyme. E.g., FAD.  Vitamin Coenzyme Metabolic role Enzyme precursor Niacin NAD, NADP -... Phosphale Oxidation-reduction Cosubstrate for Dehydrogenases Nicotinamide Adenine dinucleotide (vit. B3) ~ flavin Adenine dinucleotide Riboflavin FAD, FMN Oxidation-reduction Prosthetic group for Flavoenzymes ↳ flavin mononucleotide (vit.B2) Thiamine Prosthetic group for some TPP > Thiamine pyrophosphate Acetyl group transfer (vit. B1) carboxylases & transketolase - Pantothenic Acyl group transfer CoA > Coenzyme A Cosubstrate for many enzymes acid (vit. B5) - Pyridoxine, Amino group transfer pyridoxal or Prosthetic group for Transaminases PLP > Pyridoxal phosphate & Decarboxylation of pyridoxamine & Decarboxylases - amino acids (vit. B6) > -Cosubstrate for Dihydrofolate Tetrahydrofolate Folic acid One-carbon transfer - - reductase and others -- Methyl group Prosthetic group for Methylcobalamin Cobalamin transfer Homocysteine methyltransferase Adenosylcobalamin (vit. B12) Intermolecular Methylmalonyl-CoA mutase rearrangements Prosthetic group for lipoamide Lipoic acid Acyl transfer Dihydrolipoamide acyltransferases Proenzyme (Zymogen): The inactive precursor&form of some enzymes > pepsin (e.g., many digestive enzymes) that will be activated by cleavage of a specific peptide in its - structure If adive all the time ex : the it will digest every - can receive coenzymes  Active site: A region of an enzyme consisting of a specific - - arrangement of the amino acids side chains (R groups) where a specific substrate binds and - catalysis occurs. - - - c - ioone + - O = - Allosteric site: a region of the enzyme, other than the active site, where small molecules bind and produce a change in the activity of the active site by changing the conformation of the X enzyme. inhibit bird Subtraces) is - %5 of substrate As a result, the active site becomes either more active or less active. This increases or decreases the affinity of the - - enzyme for the substrate > Key concepts Enzymes are proteins that act as catalysts - molecules that can accelerate the rate of a reaction. Enzymes are important for diagnosis, monitoring prognosis, treatment and toxicology. Enzymes have recommended names and official names with EC numbers & are classified into six major classes. Enzymes are specific for various substrates, due to the selective nature of the binding sites on the enzyme. Substrate, product, apoenzyme, holoenzyme, cofactor, coenzyme, active site and allosteric site, are terms used in the study of enzymes. There are many differences between enzymes and inorganic catalysts  Recommended Readings 1. Biochemistry ( Lippincott’s Illustrated Review) Editors: Pamela C. Champe Publisher: Lippinoctt- Raven 2. Textbook of Biochemistry with clinical correlation 4th ed. Editor: Thomas M. Devlin Publisher: Wiley-Liss 3. Marks’ Basic Medical Biochemistry ( A clinical Approach) 4th ed. Editor: Michael Liberman, Allan D. Marks Publisher: Lippincott Williams & Wilkins 4. http://web.indstate.edu/thcme/mwking/enzyme-kinetics.html 5. http://www.stolaf.edu/people/qiannini/fashanimat/enzymes 6. http://www.reachoutmichigan.org/funexperiments/quick/eric/enzymes 7. http://www.wiley.com/legacy/college/boyer/0470003790 8. http://www.lewport.wnyric.org/wanamaker/animations/Enzymes%20 activity