The Breakdown of Sugar in the Human Body by Glycolysis

Paul Hook English 202C March 14, 2012

Audience and Scope of Description The purpose of this article is to give a brief overview of glycolysis, one of the major processes involved in the conversion of sugar to energy in the human body. This overview will allow readers to be able to identify the final products of glycolysis, the total energy yield and what steps produce that energy, and some of the key enzymes and intermediates involved. The intended audience for this document would be college freshmen in introductory life science or biochemistry classes. It could be used as part of a textbook or as supplementary material provided by the professor. This document assumes that the students are familiar with biochemical terms such as phosphorylation and kinase or will become familiar with them fairly soon after reading it. It would serve the purpose of introducing this important biochemical process without going into too many complicated details that will be elaborated on in future major classes. This document will lay the foundation for what is to come later on the students biology or biochemistry studies of glycolysis. Glycolysis: The Start of Sugar Breakdown in the Human Body Glycolysis is the process in which the human body first starts breaking down digested sugar as monomers, such as glucose (Figure 1), in order to produce energy for other bodily processes. Glucose can be derived from longer polysaccharides like sucrose and lactose. In most cells, glycolysis is just the first process of three processes (the other two being the citric acid cycle and the electron transport chain) that extract all the energy stored in glucose molecules. Figure 1. The Structure of Glucose However, in some cells like brain and sperm cells, glycolysis is the sole energy source. The overall net gain of glycolysis is two molecules of adenosine triphosphate (ATP), two molecules of nicotinamide adenine dinucleotide (NADH), and two molecules of pyruvate. ATP is used for energy elsewhere in the body, NADH is used as an electron carrier, and pyruvate is further processed in the citric acid cycle. Glycolysis consists of 10 consecutive chemical steps (Figure 2), which can be broken into two phases: a preparatory phase and a payoff phase.

Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step 7 Step 8 Step 9 Step 10

Figure 2. The Complete 10-Step Process of Glycolysis The Preparatory Phase of Glycolysis The Preparatory Phase of glycolysis consists of five steps (Figure 3): 1. The phosphorylation of glucose to glucose-6-phosphate 2. The isomerization of glucose-6-phosphate to fructose 6-phosphate 3. The phosphorylation of fructose 6-phosphate to fructose 1,6bisphosphate (FBP) 4. The cleavage of FBP to glyceraldehyde 3-phosphate and dihydroxyacetone phosphate 5. The isomerization of dihydroxyacetone phosphate to glyceraldehyde 3phosphate The main purpose of the Preparatory Phase of glycolysis is to produce two glyceraldehyde 3-phosphate molecules. This is first done through priming the glucose molecule by adding phosphate groups. These phosphate groups are derived

from the conversion of two ATP (containing 3 phosphate groups) to two ADP (containing 2 phosphate groups) in steps 1 and 3 by kinase enzymes. The cleavage reaction (Step 4) is performed by the enzyme aldolase and the isomerization reactions (Steps 2 and 5) are performed by isomerase enzymes. The net yield of the Preparatory Phase for one molecule of glucose is -2 ATP molecules and 2 glyeraldehyde 3-phosphate molecules.

Step 1

Step 2

Step 3 Step 4

Step 5 Figure 3. Preparatory Phase of Glycolysis

The Payoff Phase of Glycolysis The Payoff Phase of glycolysis consists of five steps as well (Figure 4): 6. Oxidation and phosphorylation of glyceraldehyde 3-phosphate to 1,3bisphosphoglycerate 7. Conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate 8. Mutation of 3-phosphoglycerate to 2-phosphoglycerate 9. Dehydration of 2-phosphoglyerate to phosphoenolpyruvate 10. Conversion of phosphoenolpyruvate to pyruvate The main purpose of the Payoff Phase of glycolysis is to convert the glyceraldehyde 3-phosphate molecules to two molecules of pyruvate while producing NADH and ATP. The two molecules of NADH are produced in Step 6 by a dehydrogenase enzyme through a reduction-oxidation reaction. Step 7 and Step 10 both produce two ATP molecules each through the function of kinase enzymes. The other enzymes at work in the Payoff Phase are a mutase enzyme in Step 8 and enolase enzyme used

for dehydration in Step 9. The net gain of the Payoff Phase is 4 ATP molecules, 2 NADH molecules, and two pyruvate molecules.

Step 6

Step 7

Step 8 Step 9

Step 10

Figure 4. Payoff Phase of Glycolysis The Total Net Energy Gains of Glycolysis Glycolysis has a total net gain of the energy molecules, ATP (Figure 5) and NADH (Figure 6). Even though two ATP are used per molecule of glucose during the Preparatory Phase, 4 ATP are created in the Payoff Phase, leading to a net gain of 2 ATP molecules per glucose molecule. 2 NADH are also gained through the Payoff Phase, rounding out a total net gain of 2 ATP and 2 NADH molecules per glucose molecule.

Figure 5. Structure of ATP

Figure 6. Structure of NADH

Other Ways to Enter Glycolysis Besides Through Glucose Besides glucose, there are other sugar molecules that can enter the glycolysis process at different steps. Fructose, a sugar that comes from some of the same polysaccharide sources as glucose, can enter glycolysis at Step 2 as fructose 6phosphate or can participate in a parallel process that yields glyceraldehyde 3phosphate. Another sugar, mannose, can enter glycolysis at Step 2, also as fructose 6-phosphate. Galactose, a component of lactose, can enter glycolysis by being converted to glucose 1-phosphate, which can be converted into glucose 6-phosphate and can enter as the Step 1 product. What Comes Next? The next process for energy production from glucose picks up with the two pyruvate molecules produced by glycolysis. The pyruvate molecules are converted to acetyl-CoA and oxidized to carbon dioxide by the citric acid cycle yielding 2 ATPs, 6 NADHs, and four carbon dioxide molecules. The oxidations of the citric acid cycle release electrons to electron carriers (like NADH) that participate to the final energy yielding process of the electron transport chain, which yields a maximum of 32 ATP molecules. The maximum total ATP produced by all three processes is 38 ATP. Conclusion The use of glucose for energy production in humans is initiated by the process of glycolysis. Glycolysis can be split into two phases: the Preparatory Phase and the Payoff Phase. The complete glycolysis process yields 2 ATP molecules that can be used for energy in the body, 2 NADH molecules which are used as electron carriers

and further energy production, and 2 molecules of pyruvate which are broken down further to yield more energy. Glycolysis uses a variety of enzymes including isomerases and kinases in a total of 10 steps. There are other sugar molecules that can enter in at different steps of glycolysis, but the end result is always the same: energy production. With the general outline of glycolysis as a foundation, each individual step can be explored in incredible detail and the processes that follow (citric acid cycle and electron transport chain) can be studied as well. References Information not already known to the author was summarized from the following: Nelson, David L., and Michael M. Cox. Lehninger Principles of Biochemistry. 5th ed. New York: W.H. Freeman and Company, 2008. 527-46. Print. Bailey, Regina. Cellular Respiration. About.com. <http://biology.about.com/od/cellularprocesses/a/cellrespiration.htm>. http://en.wikipedia.org/wiki/Citric_acid_cycle http://en.wikipedia.org/wiki/Electron_transport_chain Figure Sources: Cover Page: Vortistic. Flickr.com. <http://www.flickr.com/photos/vorty/3053605311/sizes/z/in/photostrea m/>. Figure 1: "Glucose." The Columbia Electronic Encyclopedia. 2005. Columbia University Press 1 Mar. 2012 <http://encyclopedia2.thefreedictionary.com/Glucose>. Figure 2: Glycolysis Overview. <https://commons.wikimedia.org/wiki/File:Glycolysis_overview.svg>. Figure 3: King, M.W. Glycolysispathway-a. Themedicalbiochemistrypage.org. 1996. <http://themedicalbiochemistrypage.org/glycolysis.php#reactions>. Figure 4: King, M.W. Glycolysispathway-b. Themedicalbiochemistrypage.org. 1996. <http://themedicalbiochemistrypage.org/glycolysis.php#reactions>.

Figure 5: Cacycle. Chemical structure of Adenosine triphosphate. <http://en.wikipedia.org/wiki/File:ATP_chemical_structure.png>. Figure 6: Structure of nicotinamide adenine dinucleotide, oxidized (NAD+). <http://en.wikipedia.org/wiki/File:NAD%2B_phys.svg>.