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Cellular Respiration Photosynthesis a process carried out by plants, uses energy from sunlight and converts it into glucose and oxygen. These products of photosynthesis are used in cellular respiration where oxygen is consumed (an aerobic process) as glucose is broken down into CO2 and H2O. Respiration means breathing but that is not its meaning in this context although the processes are related. Cellular respiration refers to an exchange of gases. In cellular respiration O2 is taken from the environment and CO2 is released supplied and removed by blood. The purpose of cellular respiration is to provide ATP for cellular work. The process is called oxidation and requires oxidization of food molecules, like glucose, to CO2 and water. The overall equation is 6C6H12O2 + 6O2 6CO2 + 6H2O + ATP. Energy is released, trapped in the form of ATP to be used for all energy-consuming activities of cells. During this process electrons are transferred from the sugar molecule to O2 making H2O. You do not see any electron transfer in the equation above. But you can see changes in H ions. Glucose molecules lose hydrogen atoms as it is converted to CO2 while O2 gains hydrogen atoms to form water. O2 is an electron grabber. It pulls harder than other atoms to get electrons. These hydrogen movements represent electron transfers because each hydrogen atom consists of one electron and one proton. Electrons move along with hydrogens from glucose to O2. It is as if they are falling. Energy is released in the process. This process is possible only because of O2 and why it is so important to life. If you stop breathingno ATP would be madeall processes stopdeath. Oxidation-Reduction Reactions/Role of Coenzymes Chemical reactions involved in the transfer of hydrogens are oxidation-reduction reactions or Redox reactions because in order for one thing to be oxidized another must be reduced. Oxidation refers to the combing of O2 with other elements. You see this everyday outside the body in rusting iron and burning wood. O2 combines with CCO2 +H20 + energy in the form of heat and light. Oxidation also occurs when H+ atoms are removed from compounds. Oxidized things lose electrons. They move to substances that more strongly attract them. The loss of electron is called oxidation. Glucose is oxidized. It loses electrons to O2. One cannot have an oxidation reaction without also having a reduction reaction. O2 is reduced. It gains electrons from glucose. When electrons change partners energy is released. When an electron is lost or a substance is oxidized, it loses energy. When an electron is gained a compound is reduced and it gains energy. As food fuels are oxidized, they lose energy. That energy is transferred to other moleculesATP. These reactions are catalyzed by enzymes called dehydrogenases which remove electrons and oxidases which transfer oxygen. These enzymes require coenzymes usually derived from B vitamins. Enzymes cannot accept H atoms therefore coenzymes act as reversible hydrogen or electron acceptors and are reduced each time a substrate is oxidized. NAD+ or niacin-nicotinamide adenine dinucleotide and FAD or flavin adenine dinucleotide made from riboflavin are the major coenzymes used in cellular respiration. Oxidation of food energy in the body must be released slowly. There is a step by step removal of pairs of H+ s or pairs of electrons from substrate molecules. Molecular O2 is the final electron acceptor. It combines with removed H atoms at the end of processH2O. Phases of Cellular Respiration Cellular respiration consists of 3 stages: glycolysis, Kreb’s cycle and electron transport chain. These three processes are related and occur in the order shown above. Glycolysis begins respiration by breaking down glucose into two molecules of pyruvic acid; a process that takes place in the cytosol of a cell and may or may not use oxygen. The Kreb’s Cycle or citric acid cycle is the complete oxidation of pyruvic acid to CO2 and water and occurs in mitochondria. The electron transport chain or oxidative phosphorylation also takes place in the mitochondria. NADH and FADH2 shuttle electrons to the electron transport chain where ATP is produced by oxidative phosphorylation. Anaerobic Respiration-Glycolysis The first step of cellular respiration is glycolysis. Glycolysis is probably the oldest known way of producing ATP. There is evidence that glycolysis predates the existence of O2 in Earth’s atmosphere and organelles in cells. Glycolysis is sometimes termed anaerobic respiration because it does not need oxygen. The process takes place in the cytoplasm of cells and occurs in all living organisms. Glycolysis does not produce large amounts of ATP. There is a net production of 2. It predominates during early minutes of high-intensity exercise. Stages of Glycolysis We can break the entire process of glycolysis into 3 stages each with several reactions. Stage 1 is a preparatory phase. It consumes energy. In this stage ATP is used to energize a molecule of glucose which is then split into two small sugars that are primed to release energy. This is sometimes termed the energy investment phase. It uses 2 ATPs and provides activation energy needed to prime later states. Glucose diffuses into cells phosphorlyated Glu6PO4 + ADP. In this reaction a PO4 group is added. Most cells do not have an enzyme to reverse this reaction and lack transport systems for phosphorylated sugars so glucose is trapped in the cell keeping glucose levels low in the body and allowing the liver to buffer blood glucose after meals. Glucose 6 Phosphate is isomerizedFructose 6 Phosphate. Fru6P + ATP fructose-1,6-disphosphate (Fru 1,6diP). Fru 1,6 diP + Aldolase (enzyme)2, 3-carbon products glyceraldehyde-3-PO4-. The molecules of glyceraldehyde-3 phosphate enter the second stage of the glycolytic process which yields an energy payoff for the cell. Glyceraldehyde-3-P dehydrogenase catalyzes the NAD+ dependent oxidation of glyceraldehyde 3P 1,3 diphosphoglycerate + 2 NADH. In this reaction an H+ is removed and picked up by NAD+NADH + H+. This NADH will continue on to the electron transport chain. In the third and last stage of glycolysis ATP and pyruvate are produced. 1,3 diphosphoglycerate + ADP3 phosphoglycerate + 2 ATPs. 3phosphoglycerate2 phosphoglycerate. 2 phsophoglycerate splits off water phosphoenolpyruvate. Phosophoenolpyruvate + ADP2 pyruvate + 2ATPs. Final products of glycolysis: 2 pyruvic acids-C3H4O3 + 4 ATP + 2 NADH + H+ + 2H2O. In total 4 ATPs are made in a process called substrate level phosphorylation. The net ATP produced is 2 because for each molecule of glucose 2 ATPs are consumed. Pyruvate is an important branch point in glucose metabolism. Its fate depends on oxygen availability. Glycolysis requires NAD+ which must be regenerated from NADH to maintain the pathway. During aerobic glycolysis when oxygen is present the electrons of NADH are transferred to mitochondrial carriers of the oxidative phosphorylation pathway generating a continuous pool of NAD+ and glycolysis continues. When there is not enough oxygen, NAD+ is regenerated by converting pyruvate to lactic acid. When O2 is available lactic acidpyruvic acid oxidation enters aerobic pathways-Krebs cycle & ETC. Anaerobic metabolism is limited by the buildup of lactic acid which begins in minutes. A build up of lactic acid disrupts the acid base balance in the body. It degrades athletic performance by impairing muscle cell contraction and produces physical discomfort. Glycolysis is used only for short bursts of high level activity lasting several minutes at most. This process cannot supply ATP for longer, endurance activities. They require aerobic metabolism. Citric Acid Cycle A specific mechanism transports pyruvate into mitochondria where aerobic processes occur. Once pyruvic acid is in a mitochondrion, a multi-enzyme complex converts pyruvateacetyl CoA, a 2 carbon metabolite. During these reactions pyruvate is decarboxylated that is carbon is removed and released as CO2. CO2 diffuses out of cells into blood and travels to the lungs where it is expelled. For each molecule of glucose oxidized two molecules of acetyl CoA enter the citric acid cycle. This is a major branch point in metabolism. Acetyl CoA can be converted into fatty acids, amino acids or made into energy. The Krebs cycle was named for its discoverer Hans Krebs. It is often called the citric acid or the tricarboxylic acid cycle. The process requires oxygen and therefore is termed aerobic and occurs in mitochondria. The cycle begins and ends with oxaloacetate. The two carbons of acetyl CoA’s condense with the 4 carbons of oxaloacetate forming a 6 carbon molecule called citrate. This is the first substrate of the citric acid cycle. The cycle continues around several successive steps in which atoms of citric acid are rearranged producing different intermediates called keto acids. Steps of the Citric Acid Cycle Acetyl CoA + oxalocitratecitric acid. Citrateisocitrate. Isocitrate + isocitrate dehydrogenase ketoglutaric acid + NADH + CO2. ketoglutarate + ketoglutarate dehydrogenasesuccinyl CoA + NADH +CO2. Succinyl CoA + succinyl CoA synthetasesuccinic acid + GTP. Succinate + succinate dehydrogenase fumaric acid + FADH2 . Fumaric acid malic acid + NADH. Malate + malate dehydrogenase oxaloacaetic acid. In summary there are 2 decarboxylations and 4 oxidations per turn of the cycle. 2 CO2, 3 NADH, 1 FADH2, and 1 GTP are produced for each acetyl CoA that enters the cycle. NADH & FADH2 are called reducing equivalents and are used to carry electrons to the electron transport chain, where more energy can be harvested from them via further oxidization reactions. Krebs cycle intermediates can be siphoned off and turned into fatty acids & nonessential amino acids. Oxidative Phosphorylation/Electron Transport Chain The final stage of cellular respiration is oxidative phosphorylation which involves the electron transport chain, chemiosmosis and takes place on the inner mitochondrial membrane. Oxygen is required. Unlike anaerobic ATP production oxidative phosphorylation produces a tremendous amount of energy. It is the primary method of energy production. The electron transport chain transfers pairs of electrons from entering substrates to oxygen. Oxidative phosphorylation captures free energy released during electron transport and couples it to the rephosphorylation of ADP to make ATP. The electron transport chain consists of a system of electron carriers embedded into the inner membrane of mitochondria. Many compounds making up the electron transport chain belong to a special group of chemicals called cytochromes. Mitochondria have dual membranes; an inner one with numerous invaginations or cristae which increase the available surface area and are only permeable to water, oxygen and CO2 and with thousands of ATP synthase complexes. Electrons captured in NADH and FADH2 are transported or passed from one compound to the next in the electron transfer chain. As electrons are transferred energy is harvested and stored by forming ATP. Carriers pass electrons from one compound to the next via a series of redox reactions. First the membrane accepts electrons and then donates them to the next acceptor with each transfer resulting in the release of a great deal of energy. Pumping of electrons (H+) back and forth across the mitochondrial membrane is the key to this process. Hydrogen ions are pumped from where they are less concentrated to where they are more concentrated. They are transported from the matrix to the intermembrane space of the mitochondrion. This hydrogen ion gradient stores potential energy. ATP synthase enzymes built into the inner mitochondrial membrane act like mini turbines and make ATP as hydrogen ions are driven back across the membrane by the energy of the concentration gradient. Since the membrane is not permeable to hydrogen ions they can only cross via a channel in the membrane. ATP synthase has a channel through which the hydrogen ions can pass. This process is called chemioosmosis. The synthase attaches phosphate groups to ADP molecules producing ATP. The last step in the electron transport chain occurs when used up electrons, along with spare hydrogen ions combine with O2, the final acceptor, to form water. Energy Yield All of the three steps of glucose oxidation are interrelated. Glycolysis makes pyruvic acid which feeds into the citric acid cycle which makes reducing equivalents (NADH & FADH2) that enter the electron transport chain. Electrons captured in NADH and FADH2 are transported or passed from one compound to the next in the electron transport chain and energy is harvested and stored by forming ATP. For each molecule of NADH approximately 3 molecules of ATP formed, and for each molecule of FADH2, about 2 molecules of ATP are formed. Glycolysis produces 4 ATPs, 2 of which are used in the reaction for a net of 2 ATP. It makes 2 NADH which in the electron transport chain yield 6 ATPs. The citric acid cycle produces 2 GTP (ATP equivalents) and 8 NADH24 ATPs and 2 FADH24 ATPs resulting in 38 ATPs. The complete oxidation of 1 mole of glucose to CO2 and H2O yields a total of 38 ATP molecules. Fermentation Another way certain cells harvest energy from food is fermentation. During fermentation pyruvic acid made by glycolysis is turned into a waste product and 2 ATP molecules. Formation of the waste product supplies NAD+ needed to carry out glycolysis. Two of the most common types of fermentation are lactic acid fermentation and alcohol fermentation. They are named for the waste products they produce that is either lactic acid or ethanol and CO2. Lactic acid fermentation is carried out by yeast, some fungi, some bacteria like Lactobacillus acidophilus found in yogurt, and sometimes by muscles. Normally muscles do cellular respiration like the rest of the body, using O2 supplied by the lungs and blood. Under greater exertion when oxygen supplies can’t get to the muscles fast enough to meet their needs, muscles can do lactic acid fermentation. Moderate activities such as sitting use aerobic respiration. But activities such as running to class uses anaerobic respiration because you are spending ATPs at a rate outpacing the delivery of O2 to tissues from the lungs. Muscles have enough ATP to support activity for about 5 seconds. Creatinine phosphate keeps one going another 10 seconds; if you are not to class by then aerobic respiration kicks in. In the process of lactic acid fermentation pyruvic acid moleculeslactic acid. Lactic acid in muscles makes them sore. Once muscles form lactic acid, they can’t do anything else with it, so until it is gradually washed away by the blood stream and carried to the liver which is able to get rid of it by turning it back to pyruvic acid and requires O2 (why you have heavy breathing after exercise to repay the O2 debt), over-exerted muscles feel stiff and sore even if they haven’t been physically injured. Alcohol fermentation is performed by yeast and some bacteria. The waste products are ethanol and CO2. Humans have long taken advantage of this process in making bread, beer, and wine. In bread making, it is the CO2 that becomes trapped between gluten (long proteins in wheat) molecules that causes bread to rise, and ethanol-abbreviated EtOH evaporating that gives it its smell while baking. The effects of ethanol in beer and wine are familiar to some of us. It is the CO2 produced by fermentation that makes these beverages effervescent. Faculative anaerobes can use both aerobic metabolism and anaerobic methods to harvest energy from food. Obligate anaerobes such as tetanus are poisoned by O2 and carry out only anaerobic metabolism. Other Organic Molecules used in Cellular Respiration We have discussed how glucose is used to make ATP to provide energy for all of the work that cells do. Glucose is a component of carbohydrate. The diet of humans consists of many molecules besides carbohydrates. These molecules can be used as fuel to make ATP. Complex carbohydrates once eaten are broken down into simple sugars such as glucose which directly enter glycolysis. Fats are broken into fatty acids and glycerol. Fatty acids can be converted into acetyl CoA and enter the citric acid cycle while glycerol can be converted to a byproduct of the glycolytic cycle, glucose 3 phosphate and enter glycolysis at that level. Proteins are broken into amino acids which can enter the citric acid cycle.