Role of ATP in Supporting Energy to the Body Essay Example for Free

Role of ATP in Supporting Energy to the Body Essay When food is ingested, it is broken down into components and utilized in a specific manner in three major cellular pathways to provide energy for the cells and the body.   Ultimately, these pathways involve the breakdown and utilization of food, the utilization of O2 and the production of CO2, the generation and regeneration of ATP and the production of water.   Therefore, these processes involve respiration as well as the breakdown and utilization of food and oxygen. Three major pathways are involved:   glycolysis which takes place in the cellular cytoplasm and breaks down glycogen and glucose from food, the Krebs Cycle which occurs in the mitochondrion and oxidative phosphorylation which occurs in the mitochondrion.   Ã‚  Ã‚   These three pathways occur in two cellular locations.   Glycolysis takes place in the cytoplasm and The Krebs Cycle and oxidative phosphorylation take place in the mitochondria.   During these three pathways, there is a utilization and production of ATP that biochemists follow closely.   It results in the net production of 36 molecules of ATP.   Ã‚  Ã‚  Ã‚   To understand the entire process that illustrates how food is broken down and utilized in the body, it is instructive to follow a bolus, that is, food consumed, chewed and swallowed.   Each step involves some aspect of digestion that breaks down complex sugar and protein molecules into smaller units.   Proteins are broken down into peptides and amino acids while starches and other complex sugars are broken down into glucose. The glucose undergoes glycolysis in the cellular cytoplasm beginning with the enzyme hexokinase, and the entire process of glycolysis is controlled by the rate limiting enzyme phosphofructokinase (PFK).   Kinase enzymes (enzymes that break down ATP) are common all along the three pathways involved, glycolysis, the Krebs Cycle (also called the Citric Acid Cycle and the Tricaroxylic Acid Cycle) and phosphorylative oxidation.   Kinases are enzymes that break down or utilized ATP, ADP and AMP as their substrate or one of their substrates.   Ã‚  Ã‚  Ã‚   Fiske and Subbarow discovered and characterized ATP in 1929.   At that time, the work of some demonstrated that the breakdown of ATP provided energy for muscle contraction, but other studies demonstrated that there was ATP synthesis during glycolysis and during electron transport.   Although ATP is made throughout the cell, the cellular location of ATP synthesis varies with the biochemical pathways associated with ATP synthesis.    Although one common pathway of ATP synthesis and breakdown is associated with the adenylate kinase reaction that forms two ADP molecules from ATP and AMP, studies in the late 1920s and beyond demonstrated that ATP synthesis was also associated with glycolysis and during electron transport.   In 1949, Kennedy and Lehninger demonstrated that ATP synthesis and the citric acid cycle occur in the mitochondria.   We now recognize that ATP synthesis and breakdown can be associated with specific biochemical pathways in the cell cytoplasm and in the mitochondria.    Some enzymes are sensitive to the ratio of ATP to AMP and to the presence of ADP.   This realization led to the concept of the energy charge, the relative concentration of ATP to ADP to AMP in the cell.   An energy charge of 1.0 represents all ATP, and energy charge of 0 represents all AMP and an energy charge of 0.5 represents all ADP or equal amounts of ATP and AMP or some combination of the two.   These ratios, and thus the energy charge are important to the cell because many cellular enzymes such as PFK are sensitive to and regulated by the relative amounts of the adenine nucleotides, ATP, ADP and AMP. Glycolysis   Ã‚  Ã‚  Ã‚   Glycolysis, also referred to as the Embden-Meryhof-Parnas pathway (figure 1), is essentially the breakdown of glucose in the cytoplasm of the cell.   The glycolytic process can begin with glucose or glycogen.   During the process, glycolysis generates the high energy compounds ATP and NADH that serve as the energy sources in the cell.   Among the many cellular roles for glycolysis, it serves three central cellular functions.   First, it generates high energy molecules such as ATP and NADH. It also produces pyruvate for the Krebs cycle and a variety of three and six carbon compounds involved in the intermediary metabolism of the cell.   The rate limiting enzyme for glycolysis, that is, the key enzyme that controls the glycolytic pathway, is phosphofructokinase (PFK).   PFK is feedback inhibited by high levels of ATP which acts by lowering the affinity of the substrate F6P for PFK.   AMP can reverse the inhibitory effect of ATP rendering PFK, and thus the control of glycolysis very sensitive to the ratio of ATP/AMP in the cytoplasm.   Ã‚  Ã‚  Ã‚   The final product arising from glycolysis depends on the cellular conditions.   Whereas glycolysis begins with glucose or glycogen, it ends with the production two molecules of the three carbon compound pyruvate.   Under anaerobic conditions, pyruvate is reduced to form lactic acid or ethanol and under aerobic conditions pyruvate loses CO2 and forms the product acetyl-coenzyme A as a result of oxidation of pyruvate to carbon dioxide and water in the citric acid cycle within the mitochrondia.   Glycolysis occurs in the cellular cytoplasm and the Krebs Cycle and oxidative phosphorylation occur in the mitochondria.   Ã‚  Ã‚  Ã‚   Glycolysis results in the formation of fructose from glucose and the formation of glyceraldehyde 3-phosphate, 3-phosphoglycerate and compounds along the pathway on the way to splitting the resulting 6-carbon compound into two three carbon units of pyruvate.   In the process, NAD+ serves as a hydrogen carrier and is reduced to NADH, the oxidized form of NAD+. In the cell, the oxidation of aldehyde to carboxylic acid is very complex and strongly exergonic and is generally coupled to ATP synthesis.   Glucose goes to Glu-6-P to Fructose with the breakdown of two ATP molecules.   Fructose gives rise to glyceraldehyde-3-phosphate which is ultimately splite in a complex reaction chain to phosphoglycerate, phosphoenolpyruvate which is finally split into two molecules of pyruvate by pyruvate and the regeneration of the two ATP molecules previously utilized. Glycolysis Figure 1. Embden-Meryhof-Parnas pathway, also known as glycolysis.   Reproduced from Michael W. King, Wednesday, 22-Mar-2006. The Citric Acid Cycle   Ã‚  Ã‚  Ã‚   The Citric Acid Cycle (Figure 2) is the most complex of the three components associated with carbohydrate metabolism and the consumption of food.   It involves the following eight enzymes and the components they use as substrate:   Citrate Synthase, Aconitase, Isocitrate Dehydrogense, alpha-ketoglutarate Dehydrogenase, Succinyl-CoA Synthetase, Succinate Dehydrogenase, Fumarase, Malate Dehydrogenase.   The generation of acetyl-CoA from carbohydrates is a major control point of the Krebs cycle.   Therefore, glycolysis and the rate limiting enzyme of glycolysis, PFK, play a role in the control of the Krebs cycle.   The oxidation of an acetyl group is a difficult chemical process and may be the reason that nature developed the Tricarboxylic Acid Cycle (TCAC), also known as the Citric Acid Cycle and the Krebs Cycle. The Krebs cycle begins when the products of glycolysis leave the cytoplasm (cytosol) and enter the mitochondria.   Once glycogen or glucose have been broken down into two three carbon units of pyruvate, the pyruvate can be further broken down into a high energy compound called acetyl-CoA resulting in the production of CO2 and water.   Acetyl-CoA combines with oxaloacetate (also spelled oxalacetate) to form the 6 carbon compound citrate.   From this condensation reaction, a complex array of biochemical reactions take place that involve various molecular transformations such as isomerizations and molecular rearrangements. These various steps result in transformations from the 6-carbon condensation that gave rise to citrate and subsequent 6-carbon units of cis-aconitate, isocitrate to a five carbon unit of alpha-ketoglutarate to the four carbon units of succinate, fumarate, malate and oxaloacetate which, once regenerated is available to combine with another high energy acetyl-CoA and form another unit of citrate under the influence of the enzyme citrate synthetase.   After citrate is formed, two carbon atoms are removed as CO2 as the various TCAC intermediates are formed leading to the regeneration of the 4-carbon oxaloacetate. There are several oxidation steps on the way to the reformation of oxaloacetate.   Each step feeds reducing agents, either NADH or FADH, into the cycle on the way to regenerating oxaloacetate from citrate.   The reducing agents (or reducing equivalents) remove hydrogen from the enzyme substrates.   So, the reducing agents serve as a pool of hydrogen carriers and allow for the further synthesis of ATP during electron transport.   The TCAC results in the production of 2 ATP molecules, 10 carrier molecules and CO2 from each molecule of glucose. Glycolysis and the Krebs Cycle Figure 2. Glycolysis and the Krebs Tricarboxylic Acid Cycle (TCAC).   Reproduced  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚  Ã‚   from David R. Caprette, 2005. Electron Transport   Ã‚  Ã‚  Ã‚   The complex molecules that were reduced during the Krebs Cycle are re-oxidized by means of the electron transport system. (Figure 3)   Although TCAC results in the production of 2 ATP molecules from each molecule of glucose, electron transport gives rise to 34 ATP molecules and water from the carrier molecules.   Therefore, the majority of the ATP in the cell must be produced in the mitochondria.   The re-oxidation of reduced NADH and FADH2 by O2 involves a sequence of electron carriers in what has become known as the electron transport chain.   It ultimately results in the generation of three molecules of ATP from ADP and inorganic phosphate for every oxygen molecule involved. This process is called oxidative phosphorylation and is the principal source of usable energy (in the form of ATP) in the cell.   It is provided by the breakdown of both carbohydrates and fats.   In the process, reduced NADH transfers a hydrogen atom plus two electrons (a hydride ion and H-).   Two complex molecules, NAD+ and FAD+, serve as the pool of hydrogen carriers and thus act reducing agents in the mitochondria; NAD+ is reduced to NADH and FAD is reduced to FADH2.   These compounds serve as electron carriers because their oxidation or reduction, the transfer of H+ (a proton), is accompanied by one or two of the electrons. The electrons donated from NADH or FADH2, upon entering this complex, travel from one carrier to the next, with each carrier being a somewhat more powerful oxidant than the previous one.   The hydrogen donated by the reducing agents combines with O2 such that with each molecule of O2 combines with 4 H+ to form water.   Therefore, two molecules of NADH must pass four electrons down the electron transport chain for each reduced oxygen molecule (O2). The chemical structures of the components of the electron transport chain fall into several distinct classes.   Most are proteins that contain special coenzymes called prosthetic groups.   Although they differ in chemical structure, a major difference between NADH and FADH2 is that NADH difuses freely between the dehydrogenases transfer hydrogen to it whereas FAD+ and FADH2 do not.   Another class of electron carriers in the mitochondrial membranes is iron-sulfur [Fe-S] clusters that are bound to proteins and release Fe3+ or Fe2+ plus H2S when acidified.   All of the carriers only appear to carry one electron at a time.   Ã‚  Ã‚  Ã‚   Ubiquinone or Coenzyme Q is a third hydrogen carrier localized in the mitochondrial membranes.   It is a common electron carrier that collects electrons from three or more points of input along the electron transport chain and passes them to molecular oxygen.   Unlike the other mitochondrial electron carriers, ubiquinone is not uniquely associated with proteins.   The cytochromes are a final class of electron carrier localized in the mitochondrial membrane.   Cytochromes are small, chemically distinct proteins that contain heme.   Like the other electron transport agents, the cytochromes only carry a single electron.   Cytochromes pass electrons from cyt bcyt ccyt acyt a3O2 Electron Transport/Oxidative Phosphorylation Figure 3.   Electron Transport during Oxidative Phosphorylation.   Reproduced from M. W. King, 2001. Summary   Ã‚  Ã‚  Ã‚   The pathways discussed here involve food consumption and energy utilization arising from food consumption.   Once food is taken in and reaches the stomach, it enters the body and the cells of the body.   Before digestion, food consists of complex, long chain molecules that must be broken during digestion beginning in the mouth and continuing in the stomach.   Once digested food reaches the cells, long chain molecules such as starch and other complex carbohydrates are further broken down into glucose.   Glucose, a six carbon compound, undergoes the process of glycolysis in the cellular cytoplasm to become two three carbon units of pyruvate. Under anaerobic conditions, pyruvate goes to lactic acid or ethanol, but in the presence of oxygen, pyruvate breaks down into a two-carbon compound, Acetyl-CoA and enters the Krebs Cycle.   There, food can be used to form energy for the cell in the form of ATP.   In the mitochondria, 36 molecules of ATP are formed for each molecule of O2.   Two ATP molecules arise from the Krebs cycle and 34 molecules arise from electron transport for each molecule of oxygen.   Thus, food consumed and oxygen taken in combine to replenish the energy supplies in the body in the form of ATP. References Caprette, David R.   Substrate Oxidation:   Krebs Reactions.   Experimental Biosciences 31 May, 2005.   The Krebs Cycle:   http://www.ruf.rice.edu/~bioslabs/studies/mitochondria/mitokrebs.html, Thursday, 7 June 2007. King, Michael W. Digestion of Dietary Carbohydrates.   Wednesday, 22-Mar-2006 Glycolysis: http://web.indstate.edu/thcme/mwking/glycolysis.html, Thursday, 7 June 2007 King, Michael W. Principals of Reduction/Oxidation (Redox) Reactions. Friday, 30 Mar-2007.   Oxidative Phosphorylation:   http://web.indstate.edu/thcme/mwking/oxidative-phosphorylation.html, Thursday, 7 June 2007.