Cellular Metabolism Chapter 4 Cellular Metabolism Cellular metabolism refers to all of the chemical processes that occur inside living cells. Energy Energy can exist in two states: Kinetic energy – energy of motion. Potential energy – stored energy. Chemical energy – potential energy stored in bonds, released when bonds are broken. Energy can be transformed form one state to another. Energy The ultimate source of energy for most living things is the sun. Laws of Thermodynamics First law of thermodynamics – energy cannot be created or destroyed – only transformed. Second law of thermodynamics – a closed system moves toward entropy, increasing disorder. Living systems are open systems that maintain organization and increase it during development. Free Energy Free energy – the energy available for doing work. Most chemical reactions release free energy – they are exergonic. Downhill Some reactions require the input of free energy – they are endergonic. Uphill Enzymes Bonds must be destabilized before any reaction can occur – even exergonic. Activation energy must be supplied so that the bond will break. Heat – increases rate at which molecules collide. Catalysts can lower activation energy. Enzymes Catalysts are chemical substances that speed up a reaction without affecting the products. Catalysts are not used up or changed in any way during the reaction. Enzymes are important catalysts in living organisms. Enzymes Enzymes reduce the amount of activation energy required for a reaction to proceed. Enzymes are not used up or altered. Products are not altered. Energy released is the same. Enzymes Enzymes may be pure proteins or proteins plus cofactors such as metallic ions or coenzymes, organic group that contain groups derived from vitamins. Enzyme Function An enzyme works by binding with its substrate, the molecule whose reaction is catalyzed. The active site is the location on the enzyme where the substrate fits. Enzyme + Substrate = ES complex. Enzyme Specificity Enzymes are highly specific. There is an exact molecular fit between enzyme and substrate. Some enzymes work with only one substrate, others work with a group of molecules. Succinic dehydrogenase oxidizes only succinic acid. Proteases will act on any protein, although they still have a specific point of attack. Enzyme-Catalyzed Reactions Enzyme-catalyzed reactions are reversible. Indicated by double arrows in reactions. Tend to go mostly in one direction. Reactions tend to be catalyzed by different enzymes for each direction. Catabolic (degradation) reaction catalyzed by enzyme A. Anabolic (synthesis) reaction catalyzed by enzyme B. Importance of ATP Endergonic reactions require energy to proceed. Coupling an energy-requiring reaction with an energy-yielding reaction can drive endergonic reactions. ATP is the most common intermediate in coupled reactions. Importance of ATP ATP consists of adenosine (adenine + ribose) and a triphosphate group. The bonds between the phosphate groups are high energy bonds. A-P~P~P Importance of ATP Phosphates have negative charges. Takes lots of energy to hold 3 in a row! Ready to spring apart. So, ATP is very reactive. Importance of ATP A coupled reaction is a system of two reactions linked by an energy shuttle – ATP. Substrate B is a fuel – like glucose or lipid. ATP is not a storehouse of energy – used as soon as it’s available. Oxidation – Reduction Redox An atom that loses an electron has been oxidized. Oxygen is a common electron acceptor. An atom that gains an electron has been reduced. Higher energy. Redox Reactions Redox reactions always occur in pairs. One atom loses the electron, the other gains the electron. Energy is transferred from one atom to another via redox reactions. Cellular Respiration Cellular respiration – the oxidation of food molecules to obtain energy. Electrons are stripped away. Different from breathing (respiration). Cellular Respiration Aerobic versus Anaerobic Metabolism Heterotrophs Aerobes: Use molecular oxygen as the final electron acceptor Anaerobes: Use other molecules as final electron acceptor Energy yield much lower ATP yield Cellular Respiration When oxygen acts as the final electron acceptor (aerobes): Almost 20 times more energy is released than if another acceptor is used (anaerobes). Advantage of aerobic metabolism: Smaller quantity of food required to maintain given rate of metabolism. Aerobic Respiration In aerobic respiration, ATP forms as electrons are harvested, transferred along the electron transport chain and eventually donated to O2 gas. Oxygen is required! Glucose is completely oxidized. C6H12O6 + 6O2 Glucose Oxygen 6CO2 + 6H2O + energy (heat or ATP) Carbon Water Dioxide Cellular Respiration - 3 Stages Food is digested to break it into smaller pieces – no energy production here. Glycolysis – coupled reactions used to make ATP. Occurs in cytoplasm Doesn’t require O2 Oxidation – harvests electrons and uses their energy to power ATP production. Only in mitochondria More powerful Anaerobic Respiration Anaerobic respiration occurs in the absence of oxygen. Different electron acceptors are used instead of oxygen (sulfur, or nitrate). Sugars are not completely oxidized, so it doesn’t generate as much ATP. Glycolysis Glycolysis – the first stage in cellular respiration. A series of enzyme catalyzed reactions. Glucose converted to pyruvic acid. Small number of ATPs made (2 per glucose molecule), but it is possible in the absence of oxygen. All living organisms use glycolysis. Glycolysis Uphill portion primes the fuel with phosphates. Uses 2 ATPs Fuel is cleaved into 3-C sugars which undergo oxidation. NAD+ accepts e-s & 1 H+ to produce NADH NADH serves as a carrier to move high energy e-s to the final electron transport chain. Downhill portion produces 2 ATPs per 3-C sugar (4 total). Net production of 2 ATPs per glucose molecule. Glycolysis Summary of the enzymatically catalyzed reactions in glycolysis: Glucose + 2ADP + 2Pi + 2 NAD+ 2ATP 2 Pyruvic acid + 2 NADH + http://www.youtube.com/watch?v=3GTjQTqUuOw&list=FL9N_Px072WuVorSwDfqf-9w&index=4&feature=plpp Harvesting Electrons form Chemical Bonds When oxygen is available, a second oxidative stage of cellular respiration takes place. First step – oxidize the 3-carbon pyruvate in the mitochondria forming Acetyl-CoA. Next, Acetyl-CoA is oxidized in the Krebs cycle. Producing Acetyl-CoA The 3-carbon pyruvate loses a carbon producing an acetyl group. Electrons are transferred to NAD+ forming NADH. The acetyl group combines with CoA forming Acetyl-CoA. Ready for use in Krebs cycle. The Krebs Cycle The Krebs cycle is the next stage in oxidative respiration and takes place in the mitochondria. Acetyl-CoA joins cycle, binding to a 4-carbon molecule to form a 6-carbon molecule. 2 carbons removed as CO2, their electrons donated to NAD+, 4-carbon molecules left. 2 NADH produced. More electrons are extracted and the original 4-carbon material is regenerated. 1 ATP, 1 NADH, and 1 FADH2 produced. The Krebs Cycle Each glucose provides 2 pyruvates, therefore 2 turns of the Krebs cycle. Glucose is completely consumed during cellular respiration. The Krebs Cycle Acetyl unit + 3 NAD+ + FAD + ADP + Pi NADH + FADH2 + ATP http://www.youtube.com/watch?v=-cDFYXc9Wko 2 CO2 + 3 Using Electrons to Make ATP NADH & FADH2 contain energized electrons. NADH molecules carry their electrons to the inner mitochondrial membrane where they transfer electrons to a series of membrane bound proteins – the electron transport chain. Building an Electrochemical Gradient In eukaryotes, aerobic metabolism takes place in the mitochondria in virtually all cells. The Krebs cycle occurs in the matrix, or internal compartment of the mitochondrion. Protons (H+) are pumped out of the matrix into the intermembrane space. Producing ATPChemiosmosis A strong gradient with many protons outside the matrix and few inside is set up. Protons are driven back into the matrix. They must pass through special channels that will drive synthesis of ATP. Oxidative phosphorylation Electron Transport Review http://www.youtube.com/watch?v=kN5MtqAB_Yc&list=FL9N_Px072WuVorSwDfqf-9w&index=2&feature=plpp Review of Cellular Respiration 1 ATP generated for each proton pump activated by the electron transport chain. NADH activates 3 pumps. FADH2 activates 2 pumps. The 2 NADH produced during glycolysis must be transported across the mitochondrial membrane using 2 ATP. Net ATP production = 4 Glucose + 2 ATP + 36 ADP + 36 Pi + 6 O2 6CO2 + 2 ADP + 36 ATP + 6 H2O Fermentation In the absence of oxygen, the end-product of glycolysis, pyruvate, is used in fermentation. During glycolysis, all the NAD+ becomes saturated with electrons (NADH). When this happens, glycolysis will stop. 2 NADH and 2 ATP produced. Pyruvate is used as the electron acceptor resetting the NAD+ for use in glycolysis. Fermentation – 2 Types Animals add extracted electrons to pyruvate forming lactate. Reversible when oxygen becomes available. Muscle fatigue Yeasts, single-celled fungi, produce ethanol. Present in wine & beer. Alcoholic fermentation Metabolism of Lipids Triglycerides are broken down into glycerol and 3 fatty acid chains. Glycerol enters glycolysis. Fatty acids are oxidized and 2-C molecules break off as acetyl-CoA. Oxidation of one 18-C stearic acid will net 146 ATP. Oxidation of three glucose (18 Cs) nets 108 ATP. Glycerol nets 22 ATP, so 1 triglyceride nets 462 ATP. Metabolism of Proteins Proteins digested in the gut into amino acids which are then absorbed into blood and extracellular fluid. Excess proteins can serve as fuel like carbohydrates and fats. Nitrogen is removed producing carbon skeletons and ammonia. Carbon skeletons oxidized. Metabolism of Proteins Ammonia is highly toxic, but soluble. Can be excreted by aquatic organisms as ammonia. Terrestrial organisms must detoxify it first. Regulating Cellular Respiration Rate of cellular respiration slows down when your cells have enough ATP. Enzymes that are important early in the process have an allosteric (regulating) site that will bind to ATP. When lots of ATP is present, it will bind to this site, changing the shape of the enzyme, halting cellular respiration. Regulating Cellular Respiration Enzyme activity is controlled by presence or absence of metabolites that cause conformational changes in enzymes. Improves or decreases effectiveness as catalyst.