Chapter 21 Enzymes and Vitamins Chapter 21 Table of Contents 21.1 21.2 21.3 21.4 21.5 21.6 21.7. 21.8 21.9 21.10 21.11 21.12 21.13 21.14 21.15 General Characteristics of Enzymes Enzyme Structure Nomenclature and Classification of Enzymes Models of Enzyme Action Enzyme Specificity Factors That Affect Enzyme Activity Extremozymes Enzyme Inhibition Regulation of Enzyme Activity Prescription Drugs That Inhibit Enzyme Activity Medical Uses of Enzymes General Characteristics of Vitamins Water-Soluble Vitamins: Vitamin C Water-Soluble Vitamins: The B Vitamins Fat-Soluble Vitamins Copyright © Cengage Learning. All rights reserved 2 Section 21.1 General Characteristics of Enzymes • Enzymes are usually proteins that act as biological catalysts. • Each cell in the human body contains thousands of different enzymes. • Enzymes cause cellular reactions to occur millions of times faster than corresponding uncatalyzed reactions • An enzyme speeds a reaction by lowering the activation energy, changing the reaction pathway that provides a lower energy route for conversion of substrate to product. • As catalysts enzymes are not consumed in the reactions • A few enzymes are now known to be ribonucleic acids (RNA) Copyright © Cengage Learning. All rights reserved 3 Section 21.2 Enzyme Structure Simple and Conjugated Enzymes • • • Most enzymes are globular proteins; some are simple proteins, others are conjugated proteins Simple enzyme: composed only of protein (amino acid chains) It is the 3o structure of the simple enzymes that makes it biologically active Conjugated enzyme: has a non-protein part in addition to a protein part. 1. apoenzyme protein part; inactive in itself 2. cofactor /coenzyme nonprotein organic (coenzyme /co-substrate) or inorganic (cofactor) moiety; the activator; loosely bound to protein • apoenzyme + cofactor = holoenzyme (biologically active conjugated enzyme) Copyright © Cengage Learning. All rights reserved 4 Section 21.3 Nomenclature and Classification of Enzymes • Most commonly named with reference to their function – type of reaction catalyzed – identity of the substrate • A substrate is the reactant in an enzyme-catalyzed reaction: – the substrate is the substance upon which the enzyme “acts.” – e. g., In the fermentation process, sugar is converted to alcohol, therefore in this reaction sugar is the substrate Copyright © Cengage Learning. All rights reserved 5 Section 21.3 Nomenclature and Classification of Enzymes Three Important Aspects of the Naming Process 1. Suffix -ase identifies it as an enzyme – e.g., urease, sucrase, and lipase are all enzyme designations – exception: the suffix -in is still found in the names of some digestive enzymes, e.g., trypsin, chymotrypsin, and pepsin 2. Type of reaction catalyzed by an enzyme is often used as a prefix – e.g., oxidase - catalyzes an oxidation reaction, – e.g., hydrolase - catalyzes a hydrolysis reaction 3. Identity of substrate is often used in addition to the type of reaction – e.g. glucose oxidase, pyruvate carboxylase, and succinate dehydrogenase Copyright © Cengage Learning. All rights reserved 6 Section 21.3 Nomenclature and Classification of Enzymes Practice Exercise • Predict the function of the following enzymes. a. Maltase b. Lactate dehydrogenase c. Fructose oxidase d. Maleate isomerase Copyright © Cengage Learning. All rights reserved 7 Section 21.3 Nomenclature and Classification of Enzymes Practice Exercise • Predict the function of the following enzymes. a. Maltase b. Lactate dehydrogenase c. Fructose oxidase d. Maleate isomerase Answers: a. Hydrolysis of maltose; b. Removal of hydrogen from lactate ion; c. Oxidation of fructose; d. Rearrangement (isomerization) of maleate ion Copyright © Cengage Learning. All rights reserved 8 Section 21.3 Nomenclature and Classification of Enzymes Six Major Classes • Enzymes are grouped into six major classes based on the types of reactions they catalyze Class Reaction Catalyzed 1. Oxidoreductases Oxidation-reductions 2. Transferases Functional group transfer reactions 3. Hydrolases Hydrolysis reactions 4. Lyases Reactions involving addition of a group to a double bond or removal of groups to form double bonds 5. Isomerase Isomerization reactions 6. Ligases Reactions involving bond formation coupled with ATP hydrolysis Copyright © Cengage Learning. All rights reserved 9 Section 21.3 Nomenclature and Classification of Enzymes Copyright © Cengage Learning. All rights reserved 10 Section 21.3 Nomenclature and Classification of Enzymes Oxidoreductase • An oxidoreductase enzyme catalyzes an oxidation–reduction reaction: – oxidation and reduction reactions are always linked to one another – an oxidoreductase requires a coenzyme that is either oxidized or reduced as the substrate in the reaction. – e.g., lactate dehydrogenase is an oxidoreductase and NAD+ is the coenzyme in this reaction. Copyright © Cengage Learning. All rights reserved 11 Section 21.3 Nomenclature and Classification of Enzymes Transferase • A transferase is an enzyme that catalyzes the transfer of a functional group from one molecule to another • Two major subtypes: 1. kinases - catalyze transfer of a phosphate group from adenosine triphosphate (ATP) to a substrate Copyright © Cengage Learning. All rights reserved 12 Section 21.3 Nomenclature and Classification of Enzymes Transferase • A transferase is an enzyme that catalyzes the transfer of a functional group from one molecule to another • Two major subtypes: 2. transaminases catalyze transfer of an amino group to a substrate Copyright © Cengage Learning. All rights reserved 13 Section 21.3 Nomenclature and Classification of Enzymes Hydrolase • a hydrolase is an enzyme that catalyzes a hydrolysis reaction • the reaction involves addition of a water molecule to a bond to cause bond breakage • hydrolysis reactions are central to the process of digestion: – carbohydrases hydrolyze glycosidic bonds in oligo- and polysaccharides – proteases effect the breaking of peptide linkages in proteins – lipases effect the breaking of ester linkages in triacylglycerols Copyright © Cengage Learning. All rights reserved 14 Section 21.3 Nomenclature and Classification of Enzymes Lyase • A lyase is an enzyme that catalyzes the addition or the removal of a group in a manner that does not involve hydrolysis or oxidation – dehydratase: effects the removal of the components of water to form a double bond – hydratase: effects the addition of the components of water to a double bond Copyright © Cengage Learning. All rights reserved 15 Section 21.3 Nomenclature and Classification of Enzymes Lyase • A lyase is an enzyme that catalyzes the addition or the removal of a group in a manner that does not involve hydrolysis or oxidation – decarboxylase: effects the removal of carbon dioxide from a substrate – deaminase: effects the removal of ammonia from a substrate Copyright © Cengage Learning. All rights reserved 16 Section 21.3 Nomenclature and Classification of Enzymes Isomerase • An isomerase is an enzyme that catalyzes the isomerization (rearrangement of atoms) of a substrate in a reaction, converting it into a molecule isomeric with itself. racemases – conversion of D- to L- isomer or vice versa mutases – transfer of a functional group within a molecule Copyright © Cengage Learning. All rights reserved 17 Section 21.3 Nomenclature and Classification of Enzymes Ligase • A ligase is an enzyme that catalyzes the formation of a bond between two molecules involving ATP hydrolysis to ADP: – ATP hydrolysis is required because such reactions are energetically unfavorable – synthetases – formation of new bond between two substrates with participation of ATP – carboxylases – formation of new bond between substrate and carbon dioxide with participation of ATP Copyright © Cengage Learning. All rights reserved 18 Section 21.3 Nomenclature and Classification of Enzymes Practice Exercise To what main enzyme class do the enzymes that catalyze the following chemical reactions belong? Copyright © Cengage Learning. All rights reserved 19 Section 21.3 Nomenclature and Classification of Enzymes Practice Exercise To what main enzyme class do the enzymes that catalyze the following chemical reactions belong? Answers: a.Transferase b.Lyase Copyright © Cengage Learning. All rights reserved 20 Section 21.4 Models of Enzyme Action Enzyme Active Site • • Explanations of how enzymes function as catalysts in biochemical systems are based on the concepts of an enzyme active site and enzyme-substrate complex formation. The active site: relatively small part of an enzyme’s structure that is actually involved in catalysis: – – – – where substrate binds to enzyme formed due to folding and bending of the protein. usually a “crevice like” location in the enzyme some enzymes have more than one active site Copyright © Cengage Learning. All rights reserved 21 Section 21.4 Models of Enzyme Action Enzyme Substrate Complex • Intermediate reaction species formed when substrate binds with the active site • Needed for the activity of enzyme • Orientation and proximity is favorable and reaction is fast Copyright © Cengage Learning. All rights reserved 22 Section 21.4 Models of Enzyme Action Two Models for Substrate Binding to Enzyme • Lock-and-Key model: – In this model, the active site in the enzyme has a fixed, rigid geometrical conformation – only substrate of specific shape can bind with active site; a substrate whose shape and chemical nature are complementary to those of the active site can interact with the enzyme. – fails to take into account proteins’ conformational changes to accommodate a substrate molecule Copyright © Cengage Learning. All rights reserved 23 Section 21.4 Models of Enzyme Action Two Models for Substrate Binding to Enzyme • Induced Fit Model: – substrate contact with enzyme will change the shape of the active site – allows small change in space to accommodate substrate (e.g., how a hand fits into a glove) – the enzyme active site, although not exactly complementary in shape to that of the substrate, is flexible enough that it can adapt to the shape of the substrate. Copyright © Cengage Learning. All rights reserved 24 Section 21.4 Models of Enzyme Action Two Models for Substrate Binding to Enzyme Copyright © Cengage Learning. All rights reserved 25 Section 21.4 Models of Enzyme Action Forces That Determine Substrate Binding • H-bonding • Hydrophobic interactions • Electrostatic interactions Copyright © Cengage Learning. All rights reserved 26 Section 21.5 Enzyme Specificity • Absolute Specificity: – an enzyme will catalyze a particular reaction for only one substrate – this is most restrictive of all specificities (not common) – e.g., catalase is an enzyme with absolute specificity for hydrogen peroxide (H2O2) – urease absolute specificity for urea • Stereochemical Specificity: – an enzyme can distinguish between stereoisomers – chirality is inherent in an active site (amino acids are chiral compounds) – L-amino-acid oxidase - catalyzes reactions of L-amino acids but not of D-amino acids. Copyright © Cengage Learning. All rights reserved 27 Section 21.5 Enzyme Specificity • Group Specificity: – involves structurally similar compounds that have the same functional groups. – e.g., carboxypeptidase: cleaves amino acids one at a time from the carboxyl end of the peptide chain • Linkage Specificity: – involves a particular type of bond irrespective of the structural features in the vicinity of the bond – considered most general of enzyme specificities – e.g., phosphatases: hydrolyze phosphate–ester bonds in all types of phosphate esters Copyright © Cengage Learning. All rights reserved 28 Section 21.6 Factors That Affect Enzyme Activity Enzyme Activity • A measure of the rate at which enzyme converts substrate to products in a biochemical reaction • Four factors affect enzyme activity: – Temperature – pH – Substrate concentration – Enzyme concentration Copyright © Cengage Learning. All rights reserved 29 Section 21.6 Factors That Affect Enzyme Activity Temperature • Higher temperature results in higher kinetic energy which causes an increase in number of reactant collisions, therefore there is higher activity. • Optimum temperature: temperature at which the rate of enzyme- catalyzed reaction is maximum • Optimum temperature for human enzymes is 37ºC (body temperature) • Increased temperature (high fever) leads to decreased enzyme activity Copyright © Cengage Learning. All rights reserved 30 Section 21.6 Factors That Affect Enzyme Activity pH • • • • Drastic changes in pH can result in denaturation of proteins Optimum pH: pH at which enzyme has maximum activity Most enzymes have optimal activity in the pH range of 7.0 7.5 Exception: digestive enzymes – pepsin: optimum pH = 2.0 – trypsin: optimum pH = 8.0 Copyright © Cengage Learning. All rights reserved 31 Section 21.6 Factors That Affect Enzyme Activity Substrate Concentration • At a constant enzyme concentration, the enzyme activity increases with increased substrate concentration. • Enzyme saturation: the concentration at which it reaches its maximum rate and all of the active sites are full • Turnover number: number of substrate molecules converted to product per second per enzyme molecule under conditions of optimum temperature and pH Copyright © Cengage Learning. All rights reserved 32 Section 21.6 Factors That Affect Enzyme Activity Enzyme Concentration • Enzymes are not consumed in the reactions they catalyze • At a constant substrate concentration, enzyme activity increases with increase in enzyme concentration – the greater the enzyme concentration, the greater the reaction rate. Copyright © Cengage Learning. All rights reserved 33 Section 21.6 Factors That Affect Enzyme Activity Practice Exercise • Describe the effect that each of the following changes would have on the rate of a reaction that involves the substrate sucrose and the intestinal enzyme sucrase. a. b. c. d. Decreasing the sucrase concentration Increasing the sucrose concentration Lowering the temperature to 10ºC Raising the pH from 6.0 to 8.0 when the optimum pH is 6.2 Copyright © Cengage Learning. All rights reserved 34 Section 21.6 Factors That Affect Enzyme Activity Practice Exercise • Describe the effect that each of the following changes would have on the rate of a reaction that involves the substrate sucrose and the intestinal enzyme sucrase. a. b. c. d. Decreasing the sucrase concentration Increasing the sucrose concentration Lowering the temperature to 10ºC Raising the pH from 6.0 to 8.0 when the optimum pH is 6.2 Answers: a. Decrease rate b. Increase rate c. Decrease rate d. Decrease rate Copyright © Cengage Learning. All rights reserved 35 Section 21.6 Factors That Affect Enzyme Activity Copyright © Cengage Learning. All rights reserved 36 Section 21.7 Extremozymes Extremeophiles • Organisms that thrive in extreme environments. – Hydrothermophiles - thrive at 80o-122oC and high pressure. – Acidophiles - optimal growth pH <3.0. – Alkaliphiles – optimal growth pH >9.0. – Halophiles – live in highly saline conditions (>0.2 M NaCl). – Piezophiles – grow under high hydrostatic pressure. – Cryophiles – grow at temps <15oC. Extremozyme • A microbial enzyme that is active at conditions that would inactivate human enzymes as well as enzymes present in most other organisms. • Etremozymes are of high interest for industrial chemists – enzymes are heavily used in industrial processes – industrial processes require extremes of temp, pressure, and pH. Copyright © Cengage Learning. All rights reserved 37 Section 21.7 Extremozymes Extremozyme Applications • Biotechnology industry – production of enzymes for industrial applications. • Petroleum industry – oil well drilling operations • Environmental scavenging and removal of heavy metals • Environmental clean-up using genetically engineered extremophiles. • Laundry detergents used in cold wash cycles. Copyright © Cengage Learning. All rights reserved 38 Section 21.8 Enzyme Inhibition • Enzyme Inhibitor: a substance that slows down or stops the normal catalytic function of an enzyme by binding to it. • Two types of enzyme inhibitors: – Competitive Inhibitors: compete with the substrate for the same active site • will have similar charge & shape – Noncompetitive Inhibitors: do not compete with the substrate for the same active site • binds to the enzyme at a location other than active site Copyright © Cengage Learning. All rights reserved 39 Section 21.8 Enzyme Inhibition Reversible Competitive Inhibition • • • • A competitive enzyme inhibitor decreases enzyme activity by binding to the same active site as the substrate. Binds reversibly to an enzyme active site and the inhibitor remains unchanged (no reaction occurs) The enzyme - inhibitor complex formation is via weak interactions (hydrogen bonds, etc.). Competitive inhibition can be reduced by simply increasing the concentration of the substrate. Copyright © Cengage Learning. All rights reserved 40 Section 21.8 Enzyme Inhibition Reversible Noncompetitive Inhibition • • • • A noncompetitive enzyme inhibitor decreases enzyme activity by binding to a site on an enzyme other than the active site. Causes a change in the structure of the enzyme and prevents enzyme activity. Increasing the concentration of substrate does not completely overcome inhibition. Examples: heavy metal ions Pb2+, Ag+, and Hg2+. Copyright © Cengage Learning. All rights reserved 41 Section 21.8 Enzyme Inhibition Irreversible Inhibition • An irreversible enzyme inhibitor inactivates enzymes by forming a strong covalent bond with the enzyme’s active site. – the structure is not similar to enzyme’s normal substrate – the inhibitor bonds strongly and increasing substrate concentration does not reverse the inhibition process – enzyme is permanently inactivated. – e.g., chemical warfare agents (nerve gases) and organophosphate insecticides Copyright © Cengage Learning. All rights reserved 42 Section 21.8 Enzyme Inhibition Copyright © Cengage Learning. All rights reserved 43 Section 21.9 Regulation of Enzyme Activity • Enzyme activity is often regulated by the cell to conserve energy. If the cell runs out of chemical energy, it will die • Cellular processes continually produces large amounts of an enzyme and plentiful amounts of products if the processes are not regulated. • General mechanisms involved in regulation: – Proteolytic enzymes and zymogens – Covalent modification of enzymes – Feedback control regulation of enzyme activity by various substances produced within a cell • The enzymes regulated are allosteric enzymes Copyright © Cengage Learning. All rights reserved 44 Section 21.9 Regulation of Enzyme Activity Properties of Allosteric Enzymes • All allosteric enzymes have quaternary structure: • Have at least two binding sites: 1. active site - where the substrate binds lock-and-key 2. allosteric site (meaning “another site”) - where the regulator binds; distorts active site • some regulators speed up enzyme action (positive allosterism); activators • some regulators slow enzyme action (negative allosterism); inhibitors Copyright © Cengage Learning. All rights reserved 45 Section 21.9 Regulation of Enzyme Activity Copyright © Cengage Learning. All rights reserved 46 Section 21.9 Regulation of Enzyme Activity Feedback Control • A process in which activation or inhibition of the first reaction in a reaction sequence is controlled by a product of the reaction sequence. • Regulators of a particular allosteric enzyme may be: – products of entirely different pathways of reaction within the cell – compounds produced outside the cell (hormones) Feedback Control Enzyme 1 inhibited by product D A Enzyme 1 Copyright © Cengage Learning. All rights reserved B Enzyme 2 C Enzyme 3 D 47 Section 21.9 Regulation of Enzyme Activity Proteolytic Enzymes and Zymogens • Mechanism of regulation by production of enzymes in an inactive forms (zymogens). • Zymogens, also known as pro-enzymes, are “turned on” at the appropriate time and place – example: proteolytic enzymes: hydrolyze peptide bonds in proteins Copyright © Cengage Learning. All rights reserved 48 Section 21.9 Regulation of Enzyme Activity Covalent Modification of Enzymes • • A process in which enzyme activity is altered by covalently modifying the structure of the enzyme – Involves adding or removing a group from an enzyme Most common covalent modification - addition and removal of phosphate group: – phosphate group is often derived from an ATP molecule. – addition of the phosphate (phosphorylation) catalyzed by a kinase enzyme – removal of the phosphate group (dephosphorylation) catalyzed by a phosphatase enzyme. – phosphate group is added to (or removed from) the R group of a serine, tyrosine, or threonine amino acid residue in the enzyme regulated. Copyright © Cengage Learning. All rights reserved 49 Section 21.9 Regulation of Enzyme Activity • Many common prescription drugs exert their mode of action by inhibiting enzymes • Examples: – Angiotensin Converting Enzyme (ACE) inhibitors • Management of blood pressure and other heart conditions – Sulfa drugs – antibiotics (antimetabolites) – Penicillins – antibiotics • Antibiotic: a substance that kills bacteria or inhibits its growth Copyright © Cengage Learning. All rights reserved 50 Section 21.9 Regulation of Enzyme Activity ACE Inhibitors • • • Angiotensin II is an octapeptide Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu hormone that increases blood pressure via constriction of blood vessels. Angiotensin I ACE converts Angiotensin I to ACE angiotensin II in the blood. inhibitors ACE inhibitors block ACE reaction and ACE block this thus reduce blood pressure. reaction – Lisinopril is an example of a ACE inhibitor Angiotensin II Asp-Arg-Val-Tyr-Ile-His-Pro-Phe + His-Leu Copyright © Cengage Learning. All rights reserved 51 Section 21.9 Regulation of Enzyme Activity Sulfa Drugs • Derivatives of sulfanilamide • Sulfa drugs exhibit antimetabolite activities – sulfanilamide is structurally similar to PABA (p-aminobenzoic acid) which bacteria need to produce coenzyme folic acid – sulfanilamide is a competitive inhibitor of enzymes responsible for converting PABA to folic acid in bacteria – folic acid deficiency retards bacterial growth and that eventually kills them – sulfa drugs don’t affect humans because we get folic acid pre-formed from food Copyright © Cengage Learning. All rights reserved 52 Section 21.9 Regulation of Enzyme Activity Penicillins • • • • • • • Bacteria have one structural feature not found in animal cells – a cell wall. The bacterial cell wall precursor is a polymer of a repeating disaccharide unit with attached polypeptide side chains that end with a D-alanyl-D-alanine unit. Transpeptidase catalyzes the formation of peptide cross links between polysaccharide strands in bacterial cell walls Penicillin acts by complexing with the enzyme transpeptidase that is responsible for cell wall synthesis Selectively inhibits transpeptidase by covalent modification of serine residue The structural similarity between the penicillins and D-alanyl-D-alanine allows the antibiotic to act as inhibitory substrates for the transpeptidase enzyme. Since animal cells do not have cell walls, there are no such enzymes to be affected and penicillin has no effect on animal cells. Copyright © Cengage Learning. All rights reserved 53 Section 21.9 Regulation of Enzyme Activity Enzyme Kinetics: Michaelis – Menten E + Kinetics of Enzyme Action k1 k3 S ↔ ES ↔ E + P k2 k4 Michaelis- Menten Equation:: υ = (vmax) (S) Km + (S) Vmax is the turnover number When υ = ½ vmax: Km = (S) Copyright © Cengage Learning. All rights reserved 54 Section 21.9 Regulation of Enzyme Activity Enzyme Kinetics: Lineweaver – Burke Plots • • • • an alternative linear transformation of the M-M equation estimation of the value of Km is inconvenient from Michaelis Equation plot and several more convenient forms of the equation have been developed. The reciprocal of the equation, a linear form called the Lineweaver – Burke plot is used. 1/υ = Km + (S) / vmax (S) = Km / vmax (S) + (S) / vmax (S) = Km / vmax x 1 / (S) + 1 / vmax (eqn for st. line) Copyright © Cengage Learning. All rights reserved 55 Section 21.9 Regulation of Enzyme Activity Enzyme Kinetics: Copyright © Cengage Learning. All rights reserved 56 Section 21.9 Regulation of Enzyme Activity Enzyme Kinetics: Competitive inhibitor: Noncompetitive inhibitor: Uncompetitive inhibitor: - binds free E - reversible -Vmax the same - binds free E & ES complex - binds ES complex - Km increases Copyright © Cengage Learning. All rights reserved - reversible; irriversible - Vmax decreases - Km constant - irriversible -V decreases max - Km decreases 57 Section 21.10 Prescription Drugs That Inhibit Enzyme Activity Clinical Applications of Enzymes – Different cells in the body produce enzymes for the same type of reactions. – Enzymes that catalyze the same reactions but vary slightly in structure are called isoenzymes. – For example, there are five isoenzymes for lactate dehydrogenase (LDH), an enzyme that converts lactic acid to pyruvic acid. Isoenzyme Subunits Abundant in LDH1 H4 Heart kidneys LDH2 H3M Heart kidneys, brain, rbc Copyright © Cengage Learning. All rights reserved LDH3 LDH4 H2M2 HM3 Kidneys Spleen brain LDH5 M4 Liver, skeletal muscle 58 Section 21.10 Prescription Drugs That Inhibit Enzyme Activity Clinical Applications of Enzymes • Enzymes produced in certain organ/tissues if found in blood serum may indicate certain damage to that organ/tissue Serum Enzymes used in diagnosis of tissue damage Organ Condition Heart Myocardial infarction Lactate dehydrogenase (LDH ) ; Creatine kinase (CK ) ; Glutamic1 oxaloacetic 2 (GOT) transaminase Liver Cirrhosis, carcinoma, Hepatitis Glutamic pyruvic transaminase (GPT) ; Lactate dehydrogenase (LDH ) ; Alkaline phosphatase (ALP) ; GOT5 Bone Rickets, carcinoma Alkaline phosphatase (ALP) Pancreas Pancreatic diseases Amylase ; Cholinesterase ; Lipase (LPS) Prostate Carcinoma Acid phosphatase (ACP) Copyright © Cengage Learning. All rights reserved Diagnostic Enzymes 59 Section 21.10 Prescription Drugs That Inhibit Enzyme Activity Clinical Applications of Enzymes Copyright © Cengage Learning. All rights reserved 60 Section 21.2 Enzyme Structure Coenzymes / Cofactors • • • the water-soluble vitamins, which include all B-vitamins and Vitamin C, act as coenzymes or coenzyme precursors cofactors are bound to the enzyme for it to maintain the correct configuration at the active site provide additional chemically reactive functional group Copyright © Cengage Learning. All rights reserved 61 Section 21.2 Enzyme Structure Coenzymes / Cofactors Copyright © Cengage Learning. All rights reserved 62 Section 21.2 Enzyme Structure Coenzymes / Cofactors Cofactors ============================================================= Metal Ion Enzymes ------------------------------------------------------------------------------------------------------------------------Ca 2+ Thromboplastin Cu2+ Tyrosinase, cytochrome oxidase Fe2+ ; Fe3+ Cytochrome oxidase, catalase, dehydrogenase Mg2+ Pyruvate kinase Mn2+ Arginase, pyruvate carboxylase, phosphatase, succinic dehydrogenase, glycosyl transferases, cholinesterase K+ Pyruvate kinase Zn2+ Carbonic anhydrase, carboxypeptidase, lactic dehydrogenase, alcohol dehydrogenase ======================================================================== Copyright © Cengage Learning. All rights reserved 63 Section 21.12 General Characteristics of Vitamins • • • • • • • • Vitamin: An organic compound essential for proper functioning of the body Must be obtained from dietary sources because human body can’t synthesize them in enough amounts Needed in micro and milligram quantities – 1 gram of vitamin B is sufficient for 500,000 people Enough vitamin can be obtained from balanced diet Supplemental vitamins may be needed after illness Many enzymes contain vitamins as part of their structures - conjugated enzymes Two classes of vitamins – Water-Soluble and Fat-Soluble Synthetic and natural vitamins have the same function – 13 Known vitamins Copyright © Cengage Learning. All rights reserved 64 Section 21.12 General Characteristics of Vitamins Copyright © Cengage Learning. All rights reserved 65 Section 21.12 General Characteristics of Vitamins Copyright © Cengage Learning. All rights reserved 66 Section 21.12 General Characteristics of Vitamins Vitamin C • Humans, monkeys, apes and guinea pigs need dietary vitamins • Co-substrate in the formation of structural protein collagen - collagen also contains hydroxylysine and hydroxylproline. - hydroxylation of lysine and proline in collagen formation are catalyzed by enzymes that require ascorbic acid (Vit. C) and iron. - in Vit. C deficiency, hydroxylation is impaired, and the triple helix of the collagen is not assembled properly. - persons deprived of Vit. C develops scurvy, a disease whose symptoms include skin lesions, fragile blood vessels, loose teeth, and bleeding gums • Involved in metabolism of certain amino acids Copyright © Cengage Learning. All rights reserved 67 Section 21.14 Water-Soluble Vitamins: The B Vitamins • • • Major function: B Vitamins are components of many coenzymes Serve as temporary carriers of atoms or functional groups in redox and group transfer reactions associated with metabolism The preferred and alternative names for the B vitamins – Thiamin (vitamin B1) – Riboflavin (vitamin B2) – Niacin (nicotinic acid, nicotinamide, vitamin B3) – Pantothenic acid (vitamin B5) – Vitamin B6 (pyridoxine, pyridoxal, pyridoxamine) – Folate (folic acid) – Vitamin B12 (cobalamin) – Biotin •Copyright © Cengage Learning. All rights reserved 68 Section 21.14 Water-Soluble Vitamins: The B Vitamins Copyright © Cengage Learning. All rights reserved 69 Section 21.15 Fat-Soluble Vitamins Vitamins A, D, E, K • • • • Involved in plasma membrane processes More hydrocarbon like with fewer functional groups Occur in the lipid fractions of their sources Their molecules have double bonds or phenol rings, so oxidizing agents readily attack them • Destroyed by prolonged exposures to air or to the organic peroxides that develop in fats and oils turning rancid. • Because the fat-soluble vitamins are easily oxidized, they destroy oxidizing agents (which are involved in the development of coronary heart disease, genetic mutations, and cancer) Copyright © Cengage Learning. All rights reserved 70 Section 21.15 Fat-Soluble Vitamins Vitamin A • a primary alcohol of molecular formula C20H30O; occur only in the animal world, where the best sources are cod-liver oil and other fish-liver oils, animal liver and dairy products • provitamin A is found in the plant world in the form of carotenes. Provitamins have no vitamin activity; however, after ingestion in the diet, -carotene is cleaved at the central carbon-carbon double bond to give 2 molecules of Vit. A. Copyright © Cengage Learning. All rights reserved 71 Section 21.15 Fat-Soluble Vitamins Functions of Vitamin A • Vision: in the eye- vitamin A combines with opsin protein to form the visual pigment rhodopsin which further converts light energy into nerve impulses that are sent to the brain. • Regulating Cell Differentiation: a process in which immature cells change to specialized cells with function. – example: differentiation of bone marrow cells white blood cells and red blood cells. • Maintenance of the health of epithelial tissues via epithelial tissue differentiation. – lack of vitamin A causes skin surface to become drier and harder than normal. • Reproduction and Growth: in men, vitamin A participates in sperm development. In women, normal fetal development during pregnancy requires vitamin A. Copyright © Cengage Learning. All rights reserved 72 Section 21.15 Fat-Soluble Vitamins Vitamin D - Sunshine Vitamin • • • • • • The antirachitic vitamin Necessary for the normal calcification of bone tissue It controls correct ratio of Ca and P for bone mineralization (hardening) Two forms active in the body: Vitamin D2 and D3 Pigment in the skin, 7dehydrocholesterol, is a provitamin D; when irradiated by the sun becomes converted to Vit. D3 humans exposed to sunlight yearround do not require dietary Vit. D Copyright © Cengage Learning. All rights reserved 73 Section 21.15 Fat-Soluble Vitamins Vitamin E - Antisterility vitamin • Alpha-tocopherol is the most active biological active form of Vitamin E • tocopherol Greek, promoter of childbirth • functions in the body as an antioxidant in that it inhibits the oxidation of unsat’d fatty acids by O2 • Primary function: Antioxidant – protects against oxidation of other compounds Copyright © Cengage Learning. All rights reserved 74 Section 21.15 Fat-Soluble Vitamins Vitamin K - Antihemorrhagic vitamin • • • • Vit K is synthesized by bacteria that grow in colon Active in the formation of proteins involved in regulating blood clotting Deficiency may occur during the first few days after birth, because newborns lack the intestinal bacteria that produce Vit. K and because they have no store of Vit. K (it does not cross the placenta) Deficiency may also occur following antibiotic therapy that sterilizes the gut Copyright © Cengage Learning. All rights reserved 75