Lec2.pptx.pdf - The Chemistry of the Cell PDF

The Chemistry of the Cell Can be structured around 5 principles: 1. The importance of carbon 2. The importance of water 3. The importance of selectively permeable membranes 4. The importance of synthesis by polymerization of small molecules 5. The importance of self-assembly Chemistry of C...

The Chemistry of the Cell Can be structured around 5 principles: 1. The importance of carbon 2. The importance of water 3. The importance of selectively permeable membranes 4. The importance of synthesis by polymerization of small molecules 5. The importance of self-assembly Chemistry of Cells Cells – composed of water, inorganic ions and carbon-containing (organic) molecules Review: Atoms- smallest unit of the chemical elements Ionic bonds –there is transfer of e¯s from one atom to a second atom Na + Cl → Na+ + Cl− → NaCl Symbol Atomic # Atomic mass # of Chemical Bonds Hydrogen H 1 1 1 Carbon C 6 12 4 Nitrogen N 7 14 3 Oxygen O 8 16 2 Sulfur S 16 32 2 Covalent Bonds - formed when atoms share their valence e¯ s a. Nonpolar - eg. O2; H2 b. Polar - eg. H2O Nonpolar CB> Polar CB> Ionic Bond>WanderWaals Molecular Composition of Cells: a. Water –abundant molecule (≥ 70% of total cell mass) - it is polar and it can form H-bonds with each other or with polar molecules b. Inorganic ions – Na⁺, K⁺, Mg2⁺, Ca2⁺ , phosphate (HPO42¯ , Cl¯ and bicarbonate (HCO3¯) - 1% or less of the cell mass - these ions are involved in number of aspects of cell metabolism c. Organic molecules – 80-90% of the dry weight of most cells - carbohydrates, lipids, proteins, and nucleic acids Macromolecules are abundant in cells The four main families of small organic molecules in cells Biomolecules Simple forms Carbohydrates monosaccharides Proteins amino acids Nucleic acids nucleotides Lipid fatty acid and glycerol Water Molecules are Polar -This accounts for its cohesiveness, temperature-stabilizing capacity and solvent properties of water.  Polar covalent bonds… Polar molecules (such as H2O) have partial negative charge at one region of the molecule (the O atom in water) and a partial positive charge elsewhere (the H atoms in water).  …allow Hydrogen bonding Thus when water molecules are close together, their positive and negative regions are attracted to the oppositely-charged regions of nearby molecules. The force of attraction, shown here as a dotted line, is called a hydrogen bond.  Water is a good solvent When salt is added to water, the partial charges on the water molecule are attracted to the Sodium (Na+) and Chlorine (Cl-) ions The water molecules work their way into the crystal structure and between the individual ions, surrounding them and slowly dissolving the salt.  Water and Oil do not mix When oil is added to water, it cannot participate in hydrogen bonding. It disrupts the ordered water structures due to hydrogen bonds. To minimize the unfavorable interactions, oil separates from water. The van Der Waals forces may dominate between nonpolar molecules The Importance of Synthesis by Polymerization Macromolecules Are Responsible for Most of the Form and Function in Living Systems -Cells contain Three different Kinds of Macromolecules informational storage and structural  Biological Polymer Proteins Nucleic Acids Polysaccharides Kind of Informational Informational Storage Structural macromolecule Examples Enzymes, DNA, RNA Starch, Cellulose Glycogen Hormones, Antibodies Repeating Amino Acids Nucleotides Monosaccharides Monosaccharides monomers Number of 20 4 in DNA; One or a few One or a few kinds of 4 in RNA repeating units The general reaction by which a macromolecule is made Condensation reaction: H2O molecule is released Carbohydrates -the most abundant class of organic compounds found in living organisms. - include simple sugars and polysaccharides -They fill numerous roles in living things, such as the storage and transport of energy (eg: starch, glycogen) and structural components (eg: cellulose in plants and chitin). General Formula: (CH2O)n Sugars: 3 C= trioses 6 C= hexoses 4 C= tetroses 7 C= heptoses 5 C= pentoses Glucose, a simple sugar Aldoses and Ketoses OR OR D-glucose D-fructose an aldose a ketose an aldohexose a ketohexose Fig. 2-4: Stereoisomers (chirality): Mirror images – depends on an asymmetric atom. Monosaccharide classifications based on the number of carbons Number of Category Name Examples Carbons Erythrose, 4 Tetrose Threose Arabinose, Ribose, Ribulose, 5 Pentose Xylose, Xylulose, Lyxose Allose, Altrose, Fructose, Galactose, 6 Hexose Glucose, Gulose, Idose, Mannose, Sorbose, Talose, Tagatose 7 Heptose Sedoheptulose Monosaccharides Tetroses Pentoses D-Ribose D-Arabinose D-Xylose D-Lyxose D-Erythrose D-Threose The ring form of ribose is a component of ribonucleic acid (RNA). Deoxyribose, which is missing an oxygen at position 2, is a component of deoxyribonucleic acid (DNA). In nucleic acids, the hydroxyl group attached to carbon number 1 is replaced with nucleotide bases. Ribose Deoxyribose Hexoses Hexoses, such as the ones illustrated here, have the molecular formula C6H12O6. German chemist Emil Fischer (1852-1919) Identified the stereoisomers for these aldohexoses in 1894. He received the 1902 Nobel Prize for chemistry for his work. D-Glucose D-Mannose D-Galactose Sugar ring formation in aqueous solution Glucose is by far the most common carbohydrate and classified as a monosaccharide, an aldose, a hexose, and is a reducing sugar. It is also known as dextrose. -also called blood sugar as it circulates in the blood at a concentration of 65-110 mg/mL of blood. Fructose is more commonly found together with glucose and sucrose in honey and fruit juices. Fructose, along with glucose are the monosaccharides found in disaccharide, sucrose. -the most important ketose sugar - common name for fructose is levulose Disaccharides consist of two simple sugars Disaccharide descriptions and components Component Disaccharide Description monosaccharides common table glucose 1α→2 sucrose sugar fructose product of starch glucose 1α→4 maltose hydrolysis glucose galactose 1β→4 lactose main sugar in milk glucose  Disaccharides: formed by two sugar monomers Sucrose Lactose Maltose Oligosaccharide - a saccharide polymer containing a small number (typically three to ten) simple sugars - commonly found on the plasma membrane of animal cells where they can play a role in cell-cell recognition. Polysaccharides are polymers of simple sugars Many polysaccharides, unlike sugars, are insoluble in water. Dietary fiber includes polysaccharides and oligosaccharides that are resistant to digestion and absorption in the human small intestine but which are completely or partially fermented by microorganisms in the large intestine. Oligo- and polysaccharides Starch Starch is the major form of stored carbohydrate in plants. Starch is composed of a mixture of two substances: amylose, an essentially linear polysaccharide, and amylopectin, a highly branched polysaccharide. Both forms of starch are polymers of α-D-Glucose. Natural starches contain 10-20% amylose and 80-90% amylopectin. Amylose forms a colloidal dispersion in hot water (which helps to thicken gravies) whereas amylopectin is completely insoluble. Amylose molecules consist typically of 200 to 20,000 glucose units which form a helix as a result of the bond angles between the glucose units.  Amylose Amylopectin differs from amylose in being highly branched. Short side chains of about 30 glucose units are attached with 1α→6 linkages approximately every twenty to thirty glucose units along the chain. Amylopectin molecules may contain up to two million glucose units. Amylopectin The side branching chains are clustered together within the amylopectin molecule Complex oligosaccharides Glycogen Glucose is stored as glycogen in animal tissues by the process of glycogenesis. When glucose cannot be stored as glycogen or used immediately for energy, it is converted to fat. Glycogen is a polymer of α-D-Glucose identical to amylopectin, but the branches in glycogen tend to be shorter (about 13 glucose units) and more frequent. The glucose chains are organized globularly like branches of a tree originating from a pair of molecules of glycogenin, a protein with a molecular weight of 38,000 that acts as a primer at the core of the structure. Glycogen is easily converted back to glucose to provide energy. Glycogen Cellulose Cellulose is a polymer of β-D-Glucose, which in contrast to starch, is oriented with -CH2OH groups alternating above and below the plane of the cellulose molecule thus producing long, unbranched chains. The absence of side chains allows cellulose molecules to lie close together and form rigid structures. Cellulose is the major structural material of plants. Wood is largely cellulose, and cotton is almost pure cellulose. Cellulose can be hydrolyzed to its constituent glucose units by microorganisms that inhabit the digestive tract of termites and ruminants. Cellulose Chitin Chitin is an unbranched polymer of N-Acetyl-D-glucosamine. It is found in fungi and is the principal component of arthropod and lower animal exoskeletons, e.g., insect, crab, and shrimp shells. It may be regarded as a derivative of cellulose, in which the hydroxyl groups of the second carbon of each glucose unit have been replaced with acetamido (-NH(C=O)CH3) groups. Chitin Glycosaminoglycans Glycosaminoglycans are found in the lubricating fluid of the joints and as components of cartilage, synovial fluid, vitreous humor, bone,and heart valves. - are long unbranched polysaccharides containing repeating disaccharide units that contain either of two amino sugar compounds -- N- acetylgalactosamine or N-acetylglucosamine, and a uronic acid such as glucuronate (glucose where carbon six forms a carboxyl group). - are negatively charged, highly viscous molecules sometimes called mucopolysaccharides. - The physiologically most important glycosaminoglycans are hyaluronic acid, dermatan sulfate, chondroitin sulfate, heparin, heparan sulfate, and keratan sulfate. Chondroitin sulfate is composed of β-D-glucuronate linked to the third carbon of N- acetylgalactosamine-4-sulfate as illustrated here. Heparin is a complex mixture of linear polysaccharides that have anticoagulant properties. Chondroitin Sulfate Heparin II. Lipids - diverse group of non-polar biomolecules - have the ability to dissolve in organic solvents (chloroform or benzene but not in water. Three Major Roles in Cells 1. provide an important form of energy storage 2. as major component of cell membrane (great importance in cell biol 3. play important role in cell signaling as a. steroid hormones (eg. Estrogen and testosterone) b. messenger molecules – convey signals from cell surface receptors to targets within the cell. TRIGLYCERIDES/FATS -consist of three fatty acids linked to a glycerol molecule - insoluble in water and therefore accumulate as fat droplets in the cytoplasm. - can be broken down for use in energy- yielding reactions( more efficient form of energy storage than carbohydrates, yielding more than twice as much energy per weight of material broken down. Fatty acids- consist of long hydrocarbon chains, most frequently containing 16 or 18 carbon atoms, with a carboxyl group (COO-) at one end -maybe saturated or unsaturated fatty acids Saturated fatty Acids - lack double bonds (eg. Stearic acid) - common component of animal fats (solid at room T) Unsaturated fatty acids - possesing double bonds - double bonds create kinks in the molecules - found in vegetable fats(liquid at room T) Phospholipids- principal components of cell membrane - are amphipathic molecules (part water- soluble and part water-insoluble ) Figure 2.7. Structure of phospholipids Glycerol phospholipids contain two fatty acids joined to glycerol. The fatty acids may be different from each other and are designated R1 and R2. The third carbon of glycerol is joined to a phosphate group (forming phosphatidic acid), which in turn is frequently joined to another small polar molecule (forming phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, or phosphatidylinositol). In sphingomyelin, two hydrocarbon chains are bound to a polar head group formed from serine instead of glycerol. Phospholipid structure and orientation of phospholipids in membranes Figure 2.9. Cholesterol and steroid hormones Cholesterol, an important component of cell membranes, is an amphipathic molecule because of its polar hydroxyl group. Cholesterol is also a precursor to the steroid hormones, such as testosterone and estradiol (a form of estrogen). The hydrogen atoms bonded to the ring carbons are not shown in this figure. Nucleic Acids DNA and RNA- the principal informational molecules of the cell DNA - Deoxyribonucleic acid (has a unique role as the genetic material) - a double-stranded molecule consisting of two polynucleotide chains running in opposite directions - contains two purines (adenine and guanine) and two pyrimidines (cytosine and thymine). - 2′-deoxyribose sugar RNA- Ribonucleic acid - single-stranded - Adenine, guanine, and cytosine are also present in RNA, but RNA contains uracil in place of thymine - ribose sugar - different types of RNA participate in a number of cellular activities a. Messenger RNA (mRNA) -carries information from DNA to the ribosomes, where it serves as a template for protein synthesis  b. Ribosomal RNA(rRNA) involves in protein synthesis c. Transfer RNA(tRNA) *polymerization of nucleotides to form nucleic acids involves the formation of phosphodiester bonds between the 5′ phosphate of one nucleotide and the 3′ hydroxyl of another oligonucleotide - a short polymer of only a few nucleotides the large polynucleotides that make up cellular RNA and DNA may contain thousands or millions of nucleotides, respectively. Polynucleotides are always synthesized in the 5′ to 3′ direction, with a free nucleotide being added to the 3′ OH group of a growing chain. Figure 2.10. Components of nucleic acids Nucleic acids contain purine and pyrimidine bases linked to phosphorylated sugars. A nucleic acid base linked to a sugar alone is a nucleoside. Nucleotides additionally contain one or more phosphate groups. Figure 2.12. Complementary pairing between nucleic acid bases Figure 2.11. Polymerization of nucleotides A phosphodiester bond is formed between the 3′ hydroxyl group of one nucleotide and the 5′ phosphate group of another. A polynucleotide chain has a sense of direction, one end terminating in a 5′ phosphate group (the 5′ end) and the other in a 3′ hydroxyl group (the 3′ end).  ATP: the energy carrier in cells Proteins -primary responsibility is to execute the tasks directed by that information in nucleic acids -the most diverse of all macromolecules (each cell contains several thousand different proteins, which perform a wide variety of functions) 1. serving as structural components of cells and tissues 2. acting in the transport and storage of small molecules (e.g., the transport of oxygen by hemoglobin 3. transmitting information between cells (e.g., protein hormones) 4. and providing a defense against infection (e.g., antibodies) -the most fundamental property of proteins is their ability to act as enzymes -direct virtually all activities of the cell. -polymers of 20 different amino acids  Figure 2.13. Structure of amino acids Each amino acid consists of a central carbon atom (the α carbon) bonded to a hydrogen atom, a carboxyl group, an amino group, and a specific side chain (designated R). At physiological pH, both the carboxyl and amino groups are ionized, as shown. Figure 2.14. The amino acids The three-letter and one-letter abbreviations for each amino acid are indicated. The amino acids are grouped into four categories according to the properties of their side chains: nonpolar, polar, basic, and acidic. A simple amino acid: alanine  Protein structure 1. primary structure 2. secondary structure 3. tertiary structure 4. quaternary structure Primary Structure -the sequence of amino acids in its polypeptide chain Figure 2.15. Formation of a peptide bond The carboxyl group of one amino acid is linked to the amino group of a second. Figure 2.16. Amino acid sequence of insulin Secondary structure- the regular Tertiary structure-the folding of arrangement of amino acids within the polypeptide chain as a result of localized regions of the polypeptide. interactions between the side chains of amino acids that lie in different regions of the primary sequence Figure 2.19. Secondary structure of Figure 2.20. Tertiary structure of proteins ribonuclease Quaternary structure- consists of the interactions between different polypeptide chains in proteins composed of more than one polypeptide. Figure 2.21. Quaternary structure of hemoglobin Three types of noncovalent bonds that help proteins fold Proteins as polypeptide chains Proteins often have highly specific binding sites Various functions of proteins How a set of enzyme-catalyzed reactions generates a metabolic pathway Phosphorylation and ATP hydrolysis drive protein functions Bioenergetics, Enzymes and Metabolism Bioenergetics: The Flow of Energy in the Cell -the study of the various types of energy trans- formations that occur in living organisms -the prodn of energy, its storage and its use are central to the economy of the cell Energy - the capacity to do work (the capacity to change or move something). -cell require energy to do all their work, including the synthesis of sugars from CO2 and H2O in photosynthesis, the contraction of muscles and the replication of DNA POTENTIAL ENERGY - several forms of PE are biologically significant 1. stored in the bonds connecting atoms in molecules 2. concentration gradient 3. electric potential (the energy of charge separation) Cells Need Energy to Cause Six Different Kinds of Biological Work 1. Synthetic Work -changes in chemical bonds (formation and generation of new molecules) e.g. process of photosynthesis 2. Mechanical Work- physical change in the position or orientation of a cell or some part of it e.g. Contraction of weightlifter’s muscle or movement of cell thru its flagella 3. Concentration Work - movement of molecules across a membrane against a concentration gradient e.g. Na+-K+ pumps across plasma membrane 4. Electrical Work - movement of ions across a membrane against an electrochemical gradient e.g. Membrane potential of mitochondrion (generated by active proton transport) 5. Heat - an increase in temperature that is useful to warm blooded animals e.g. Use to maintain body T near 37oC where metabolism is most efficient by warm-blooded animals 6. Bioluminescence – production of light e.g. Seen during courtship of fireflies, in dino- flagellates, luminous toadstools, deep-sea fish Most organisms obtain energy either from sunlight or from organic food molecules: a. Phototrophs – “light-feeders” (plants, algae, cyanobacteria and photosynthesizing bacteria). b. Chemotrophs- “chemical-feeders” (all animals,fungi, protists and most bacteria) Energy flows through the biosphere continuously System -By convention, the restricted portion of the universe under consideration e.g. Reaction/process occurring in a beaker of chemicals or in a cell Surroundings - referred to all the rest of the universe 2 types of System: 1. Open System - can exchange energy with its surroundings - can use incoming energy to increase its orderliness thus decreasing its entropy. 2. Closed System – can not exchange energy w/ its surroundings - tends toward equilibrium and increases its entropy *All living organisms are open systems, exchanging energy freely with their surroundings. Thermodynamics -the study of the changes in energy that accompany events in the universe. 1st Law of thermodynamics (Law of conservation of Energy) - E is neither created nor destroyed but can be converted from one form to another energy stored = energy in – energy out or ∆E = Eproducts - Ereactants (chemical reactions) In the case of biological rxns and processes, we are more interested in the change in enthalpy or heat constant (H)  ∆H = ∆E + ∆(PV) = ∆E ∆H = Hproducts - Hreactants *if the heat content of the products is less than that of the reactants, ∆H will be negative and the rxn is said to be Exothermic If the heat content of the products is greater than that of reactants, ∆H will be positive and the rxn is endothermic -energy can be expressed in the same units of measurement such as cal or kilocalorie 2nd Law of thermodynamics - the universe and its parts (including living systems) become increasingly disorganized (Entropy) Energy transformations thus increased the amount of entropy of a system. *only E that is in an organized state-called free energy-can be used to do work Free energy or G- a measure of the potential energy of a system which is a function of the enthalpy (H) and entropy (S) Enthalpy(H)Heat-in a chemical rxn, the E of the reactants or products is equal to their total bond energies (heat released or absorbed during a chemical reaction) Entropy(S)- a measure of the degree of disorder or randomness in a system; the higher the entropy, the greater the disorder resulting frm a rxn -thus determines its chemical equilibrium and predicts in which direction the reaction will proceed under any given set of conditions *many biological rxns (such as synthesis of macromolecules) are thermodynamically unfavorable under cellular conditions (ΔG>0or-) (for the reaction to proceed an additional source of energy is required) A B ΔG=+10kcal/mol How?: by coupling the conversion of A to B with an energetically favorable reaction C D ΔG= -20kcal/mol THUS: A+C B + D ΔG= -10kcal/mol * Enzymes are responsible for carrying out such coupled reactions in a coordinated manner *the cell uses this basic mechanism to drive many energetically unfavorable reactions that must take place in biological system At constant T & P, it is possible to predict the direction of a chemical rxn by using G. G =H-TS where T= °K -the change in Free Energy(ΔG) determines the direction of a chemical reaction Free Energy change, ΔG = G products – G reactants if ΔG(-) for a chemical reaction, forward rxn occurs if ΔG(+) reverse reaction occurs if ΔG = 0, both forward and reverse rxns occur at equal rates; the rxn is at equilibrium A B Standard Free-Energy Change (ΔG °) ΔG° = -RTln K where K= [B]/[A]  Endergonic Reactions– chemical reactions that require input of E. eg. CO2 + H2O CH2O + O2 Exergonic Reactions-rxns that convert molecules with more free energy to molecules with less- and, therefore, that release energy as they proceed. eg. C6H12 O6 + O2 CO2 + H2O Equilibrium vs Steady State Metabolism At equilibrium: 1. reaction has stopped (no net reaction are possible) 2. no energy can be released 3. no work can be done and order of living state can not be maintained *The continual flow of oxygen and other materials into and out of cells allows cellular metabolism to exist in a Steady state. ( thus life is possible because living cells maintain this state). Coupled Reactions: ATP -Energy –liberating reactions are thus coupled to energy-requiring reactions. -Adenosine 5’-triphosphate (ATP) plays a central role in this process by acting as a store of free energy within the cell  Figure 2-24. In adenosine triphosphate (ATP), two high-energy phosphoanhydride bonds (red) link the three phosphate groups. -The bonds between the phosphates in ATP (HIGH- ENERGY BONDS) -large amount of free energy is released when hydrolyzed within the cell (≈ΔG approx = 12kcal/mol) from ATP to ADP and Pi -energy released from the breakdown of ATP is used to power the energy-requiring processes in cells. -known as the universal energy carrier, ATP serves to more efficiently couple the E released by the breakdown of food molecules to the E required by the diverse endergonic processes in the cell. Figure 2-25. The ATP cycle. ATP is formed from ADP and Pi by photosynthesis in plants and by the metabolism of energy-rich compounds in most cells. The hydrolysis of ATP to ADP and Pi is linked to many key cellular functions; the free energy released by the breaking of the phosphoanhydride bond is trapped as usable energy. Coupled Reactions: Oxidation-Reduction -involve the transfer of hydrogen atoms - a molecule is said to be oxidized when it loses electrons and it is said to be reduced when it gains electrons - a reducing agent is thus an electron donor; an oxidizing agent is an electron acceptor -although oxygen is the final electron acceptor in the cell, other molecules can act as oxidizing agents -a single molecule can be an electron acceptor in one reaction and an electron donor in another. 1. NAD and FAD can become reduced by accepting electrons from hydrogen atoms removed from other molecules 2. NADH + H+ and FADH2 in turn, donate these electrons to other molecules in other locations within the cells 3. Oxygen is the final electron acceptor (oxidizing agent) in a chain of oxidation-reduction reactions that provide energy for ATP production.  Rxn site H H + 2H +H N Nicotinamide adenine dinucleotide NAD+ NADH (Oxidized state) (Reduced state)  H O H3C N NH + 2H N H3C N O H Flavin Adenine Dinucleotide (FAD) FADH2 (Oxidized Form) (Reduced form) The Central Role of Enzymes as Biological Catalysts Enzymes—catalysts that increase the rate of virtually all the chemical reactions within cells. 2 Fundamental Properties: 1. they increase the rate of chemical reactions without themselves being consumed or permanently altered by the reaction. 2. they increase reaction rates without altering the chemical equilibrium between reactants and products. Active site -a specific region of the enzyme where the  Figure 2.23. Enzymatic catalysis of a reaction between two substrates The enzyme provides a template upon which the two substrates are brought together in the proper position and orientation to react with each other. Figure 2.24. Models of enzyme-substrate interaction (A) In the lock-and-key model, the substrate fits precisely into the Figure 2.22. Energy active site of the enzyme. (B) diagrams for catalyzed In the induced-fit model, and uncatalyzed substrate binding distorts the reactions conformations of both substrate and enzyme. This distortion brings the substrate closer to the conformation of the transition state, thereby accelerating the reaction. competitive inhibitors substances that compete with the substrate for an enzyme’s active site noncompetitive inhibitors substances that attach to a binding site on an enzyme other than the active site, causing a change in the enzyme’s shape and a loss of affinity for its substrate Prosthetic groups are small molecules bound to proteins in which they play critical functional roles -either small organic molecules (coenzymes) or inorganic like metal ions (cofactors) Coenzymes -molecules that work together with enzymes to enhance reaction rates. -are not irreversibly altered by the reactions in which they are involved but are recycled and can participate in multiple enzymatic reactions. Table 2.1. Examples of Coenzymes and Vitamins Coenzyme Related vitamin Chemical reaction NAD+, NADP+ Niacin Oxidation-reduction FAD Riboflavin (B2) Oxidation-reduction Thiamine pyrophosphate Thiamine (B1) Aldehyde group transfer Coenzyme A Pantothenate Acyl group transfer Tetrahydrofolate Folate Transfer of one-carbon groups Biotin Biotin Carboxylation Pyridoxal phosphate Pyridoxal (B6) Transamination Figure 2.29. Allosteric regulation In this example, enzyme activity is inhibited by the binding of a regulatory molecule to an allosteric site. In the absence of inhibitor, the substrate binds to the active site of the enzyme and the reaction proceeds. The binding of inhibitor to the allosteric site induces a conformational change in the enzyme and prevents substrate binding. Most allosteric enzymes consist of multiple subunits Metabolism Metabolism -all of the reactions in the body that involve energy transformation 2 Categories: 1. Anabolism – reactions require the input of energy and include the synthesis of large energy-storage molecules, including glycogen, fat and protein. 2. Catabolism – reactions release energy, usually by the breakdown of larger organic molecules into smaller molecules. *The catabolic reactions that break down glucose, fatty acid, and amino acids serve as the primary source s of energy for the synthesis of ATP. *Some of the chemical-bond energy in glucose is transferred to the chemical-bond energy in ATP. Fig.3 Three Stages of Metabolism  The Generation of ATP from Glucose -breakdown of glucose (major source of cellular energy) 2 Stages: 1. Glycolysis 2. Tricarboxylic acid (TCA) cycle Glycolysis - initial stage in the breakdown of glucose (aerobic cells) - common to all cells (occurs in the cytosol) -occurs in the absence of O2 (can provide all the metabolic energy of anaerobic organisms) - conversion of glucose to pyruvate with the net gain of 2 molecules of ATP Glu + 2ADP + 2Pi + 2NAD+ 2 Pyruvate + 2ATP + 2NADH + 2H+ +2H2O Enzymes: (important regulatory points of glycolytic pathway) 1. Hexokinase 2. phosphofructokinase- key control element which is inhibited by increased levels of ATP Figure 2.32. Reactions of glycolysis Glucose is broken down to pyruvate, with the net formation of two molecules each of ATP and NADH. Under anaerobic conditions, the NADH is reoxidized by the conversion of pyruvate to ethanol or lactate. Under aerobic conditions, pyruvate is further metabolized by the citric acid cycle. Note that a single molecule of glucose yields two molecules each (shadow boxes) of the energy-producing three-carbon derivatives. Glycogenesis – the formation of glycogen from glucose (see fig. – enzyme=glycogen synthase) Glycogenolysis- the conversion of glycogen to glucose -6-P (enzyme= glycogen phosphorylase) Gluconeogenesis- the conversion of noncarbohydrate molecules (not just lactic acid but also amino acids and glycerol) through pyruvic acid to glucose Cori Cycle - gluconeogenesis in the liver allows depleted skeletal muscle glycogen to be restored w/in 48 hrs. - it is a two-way traffic between skeletal muscles and the liver In the liver are enzymes: glu-6-phosphatase & lactic dehydrogenase  The Cori Cycle Skeletal Muscles Liver Glycogen Glycogen Exercise Rest 1 9 7 Blood Glu-6-phosphate Glucose Glu-6-phosphate 8 2 6 Pyruvic acid Pyruvic acid 3 5 Blood Lactic acid Lactic acid 4 TCA or Krebs cycle - occurs in the mitochondria (matrix) - leads to the final oxidation of the carbon atom s to carbon dioxide Figure 2.33. Oxidative decarboxylation of pyruvate.Pyruvate is converted to CO2 and acetyl CoA, and one molecule of NADH is produced in the process. Coenzyme A (CoA-SH) is a general carrier of activated acyl groups in a variety of reactions. Figure 2.34. The citric acid cycle A two-carbon acetyl group is transferred from acetyl CoA to oxaloacetate, forming citrate. Two carbons of citrate are then oxidized to CO2 and oxaloacetate is regenerated. Each turn of the cycle yields one molecule of GTP, three of NADH, and one of FADH2. Electron Transport and Oxidative Phosphorylation -built into the foldings, cristae of the inner mitochondrial membrane are a series of molecules that serve as electron transport system during aerobic respiration -the molecules of electron transport system are fixed in position within the inner mitochondrial membrane in such a way that they can pick up electrons from NADH and FADH2 and transport them in a definite sequence and direction. -the electron transport chain thus act as an oxidizing agent for NAD and FAD. Oxidative Phosphorylation - the production of ATP thru the coupling of the electron-transport system with the phosphorylation of ADP. Figure 2.35. The electron transport chain Electrons from NADH and FADH2 are transferred to O2 through a series of carriers organized into four protein complexes in the mitochondrial membrane. The free energy derived from electron transport reactions at complexes I, III, and IV is used to drive the synthesis of ATP. Chemiosmosis in mitochondria ATP Balance Sheet Summary: Theoretical ATP yield =36 to 38 ATP per glucose Actual ATP yield = 30 to 32 ATP per glucose (allowing for the costs of transport) Table 3. ATP Yield per Glucose in Aerobic Respiration Phases of Subsrate-leve Reduced Coenzymes ATP Made by Respiration l Oxidative phosphorylati Phosphorylation* on Glucose to pyruvate 2 ATP (net 2 NADH, but usually 1.5 ATP per FADH2 X 2 (in cytoplasm) gain) goes into mitochondria = 3ATP as 2 FADH2 Pyruvate to acetyl None 1 NADH (X2) = 2NADH 2.5ATP per NADH x 2 = CoA(x2 bec one glu 5ATP yields 2 pyruvates) Krebs cycle (x2 bec 1 ATP (X2) = 2 3 NADH (X2) 2.5ATP per NADH x 3 one glucose yields 2 ATP =7.5 ATP X 2 = 15 ATP Krebs cycles) 1.5 ATP per FADH2 X 2 = 3ATP SUBTOTALS 4 ATP 26 ATP GRAND TOTAL 30 ATP *Theoretical estimates of ATP production from oxidation phosphorylation are 2 ATP per FADH2 and 3 ATP per NADH. If these numbers are used, a total of 32 ATP will be calculated as arising from oxidative phosphorylation. This is increased to 34 ATP IF the cytoplasmic NADH remains as NADH when it is shuttled into the mitochondrion. Adding these numbers to the ATP made directly gives a total of 38 ATP produced from a molecule of glucose.Estimates of the actual number of ATP obtained by the cell are lower because of the costs of transporting ATP out of the mitochondria.  Glycogen Glucose Glycerol Phosphoglyceraldehyde FATS Lactic acid Pyruvic Acid Amino Fatty Acids Acetyl CoA Protein acids Ketone Urea C4 TCA C6 bodies cycle C5 Figure 5.17 The interconversion of glycogen, fat and protein Figure 2.36. Oxidation of fatty acids The fatty acid (e.g., the 16-carbon saturated fatty acid palmitate) is initially joined to coenzyme A at the cost of one molecule of ATP. Oxidation of the fatty acid then proceeds by stepwise removal of two-carbon units as acetyl CoA, coupled to the formation of one molecule each of NADH and FADH2. ATP Produced: 108 ATP Amino Acid Metabolism Transamination- type of reaction in which the amine group is transferred from one amino acid to form another Oxidative Deamination- the metabolic pathway that removes amine groups from amino acids—leaving a keto acid Essential amino acids- can not be produced by the body and ammonia (which is converted to urea). and must be obtained in the diet (lysine, tryptophan, phenylalanine, threonine, valine, methionine, leucine, isoleucine & histidine(children)) Nonessential amino acids- the body can produce them if provided with a sufficient amount of carbohydrates and the essential aas (aspartic acid, glutamic acid, proline, glycine, serine, alanine, cysteine, arginine,