Respiration - Krebs Cycle  

As discussed earlier, pyruvic acid may be oxidized when oxygen is present. This pathway is called the Kreb Cycles. Study behavioral objectives 21-22 and read the pages indicated by E-9. 

Completing Cellular  Respiration: The Krebs Cycle Reactions

 When oxygen is available for respiration, the pyruvic acid produced in the early stages of carbohydrate metabolism can be completely broken down to carbon dioxide and water. You should recall that this complete oxidation process yields maximum energy to the cell. In this chapter we will show you step-by-step how the respiration process takes place to oxidize completely the pyruvic acid molecules. You will see that this breakdown process yields far more energy than did the reactions up to the pyruvic acid stages. You will also see what happens to the hydrogen atoms which were produced along with the pyruvic acid molecules in the seven steps already described. Keep in mind that through oxidative respiration the cell obtains from the glucose molecule (click one): 

a. moderate amounts of energy 
b. large amounts of energy 
c. maximum energy yield
Krebs cycle reactions like glycolysis is a series of chemical reactions which occur in a step by step process. During each step an organic molecule is  converted to a different molecule associated  with an energy change. As the various steps are presented on this "web page",  list them  in your notes indicating the changes in biological energy. These steps will resemble a "road map" showing changes in organic molecules  and the involvement of biological energy. A difference between this pathway compared to  glycolysis is that the Krebs is a cycle. That is you will have one of the substrates (citrate) in the pathway, break it down, and reform this citrate.  The three forms of chemical biological energy involved during these reactions are ATP , NADH + H and FADH2.  

Upon completion of this "road map",  draw a input/output box in your notes indicating  what enters and leaves this pathway.  Include the organic molecules and the biological energy. 
 
 

Cellular respiration includes many complex chemical reactions, so we will simplify their representation. We will use a different notation than previously. Instead of naming each molecule in the reactions, we will simply indicate important reactants or products. We will introduce a basic carbon structure of notation for the organic molecules. Use your readings in the text to get the names of these organic molecules. This notation system changes the appearance of the reactions, since it does not use either chemical names or formulas for the reactants and products. To acquaint yourself with the notation, look at the following chart: 
 

Chemical Name Formula Notation
pyruvic acid C3H4O3 3-C
glucose C6H12O6 6-C
carbon dioxide CO2 CO2
 In the first step of the oxidative respiration of pyruvic acid, the molecule loses a carbon dioxide molecule and becomes a compound called acetyl CoA (two carbons in length). The carbon dioxide produced in the reaction leaves the cell as waste. 
Step 1: 3-C ---> 2-C + CO2

 
 

Study the figure in your text. Also during Step 1 hydrogen is being removed by a NAD coenzyme. 

 Step 1 expanded:        NAD +    3-C ---->  2-C +  NADH  +  CO2 

      This NADH will be converted into 3 ATP (Krebs Cycle  NADH form 3 
      ATP  per molecule in the cytochorme system  instead of 2 as in glycolysis). 
 

In the second step, this two-carbon molecule joins with a four carbon oxaloacaetic acid (OAA) to form a citric acid molecule. 
 

The product of Step 2 is a molecule which is six carbons long. 

   Step 2:   4-C  + 2-C  ----->   6-C 

 It may seem strange that the second step in the oxidative respiration of pyruvic acid creates a longer molecule, but after you have seen the entire process, you will understand why. 

In the third step the six-carbon molecule citrate is converted to isocitrate with little or no loss of biological energy. 

Step 3: 6-C ---> 6-C + H

 
In step four the six carbon isocitrate molecule is decarboxylated forming a five carbon alpha-ketoglutaric acid and carbon dioxide. Also more hydrogen is pulled off by a NAD coenzymecule. This is  an example of a dehydrogenation reaction, which is the removal of hydrogen from a molecule. 

You should remember that after a dehydrogenation reaction, the hydrogen atoms move to other atoms or molecules which are known as _____. 

Answer: Hydrogen acceptors such as NADH, FADH2. 

 If oxygen is present, these hydrogen acceptors  can move the the cytochrome system (CETS) where oxygen will be used and energy  acquired by the hydrogen acceptors  is  transferred  into ATP molecules. 

  Step 4:  NAD + 6-C ---> 5-C + CO2 + NADH 

 
Step five  also results in another waste carbon dioxide and a  removal of hydrogen by NAD, but this reaction differs from the previous one in that an ATP is also made directly (substrate phosphorylation). During this step alpha-ketoglutaric acid is convert into succinic acid (4 carbons) 

Step 5: ADP + NAD +  5-C ---> 4-C + CO2 + NADH + ATP 

The production of the hydrogen atoms in this step is important to the respiration process. Click the statements which correctly explain the importance of the hydrogen atoms. Each hydrogen atom produced has the potential to: 

a. be accepted by oxygen 
b. be oxidized to produce water 
c. enter an energy-releasing reaction 
 The next two reactions, Steps 6 and 7, are important because they both involve the production of hydrogen atoms by the process of dehydrogenation. Step six involves succinate(4-C) being converted into fumaric acid (4-C). However during this step the hydrogen acceptor is a different coenzyme, FAD. The FADH2 molecule formed  can also have its enegy transferred into ATP  by moving to the cytochrome system. However, only two ATP molecules will be formed for each FADH2  molecule entering the CETS. 

Step 6:  FAD +  4-C ---> 4-C + FADH2 

Between step six and seven fumaric acid in converted into malic acid with no biological energy being formed. 
  

Step seven involves malic acid being converted into oxaloacetic acid with hydrogen being removed by  the coenzyme NAD. 

Step 7: NAD +  4-C ---> 4-C + NADH 
 
 

 At this point it is important that you know the name of the four-carbon compound produced in Step 7. It is oxaloacetic  acid. 

Look back to the Step 2 reaction  and examine the chemical reaction which took place at that step. 

Why is the identity of oxaloacetic  acid produced in Step 7 so important? 

Answer: Oxaloacetic  acid is the same compound which reacted with acetyl Co. A in Step 2. This seems to indicate that the process of oxidative respiration is cyclic in nature. 

Scrutinizing the Cycle

9. The following diagram summarizes the seven steps in the oxidation of pyruvic acid presented thus far. Study the figure indicated by E-10. 

Has the pyruvic acid been used up yet by the series of reactions? To answer this question, one a can use a "bookkeeping approach" of counting atoms to examine the progress of the reactions. 

Pyruvic acid is a three-carbon compound with the chemical formula C3H4O3 One molecule of pyruvic acid enters the series of reactions at Step 1. The only other reactant shown entering the oxidative respiration process is a molecule of citric acid, which enters the reactions at Step 2. But a molecule of citric acid is produced by the reactions in Step 7. What can you say about the citric acid in the oxidative respiration of pyruvic acid at the conclusion of Step 7 of the process? (Click one.) 

a. Citric acid has been used up in the process. 
b. Citric acid has been created by the process. 
c. There has been no net change in the amount of citric acid. 
 It is impossible to tell whether the carbon atoms in the citric acid molecule released in Step 7 are the same carbons which entered the reaction in the citric acid molecule in Step 2. However. it really doesn't matter. The simple bookkeeping approach can tell us a lot about the process even without tracing the movement of each and every atom involved in the reactions. 

Since the citric acid is regenerated in the process, we need to focus our attention on the other reactant (pyruvic acid) and the products of the seven reactions. Study the figure indicated by E-11. 

 Three carbon atoms enter the reactions in a molecule of pyruvic acid. Three carbon atoms leave the reactions in molecule of carbon dioxide. It is clear the pyruvic acid molecule supplies all of the carbon and hydrogen necessary for the reactions. You can see from the bookkeeping of atoms that pyruvic acid has been completely broken down (all atoms have been transferred to product substances) by Step 7 of the process. The carbon and oxygen atoms have been given off to the environment in the form of carbon dioxide. The hydrogen atoms have been freed from the pyruvic acid molecule. What do you predict is their eventual fate in oxidative respiration? 

Answer: They will be oxidized to form water, since oxygen is available for the process. The reaction will liberate a lot of energy. This occurs in the cytochrome electron transport  system which will be investigated on  the next web page. 

 In cellular respiration, glucose is converted into pyruvic acid molecules (glycolysis)  with an accompanying release of energy. Then the pyruvic acid molecules are further broken down through a cycle of chemical reactions (Krebs Cycle). This set of reactions is usually called the citric acid cycle, but it may also be termed the Krebs Cycle or tricarboxylic acid cycle. The illustration below demonstrates the cyclic nature of the process, as the citric acid enters the reaction in the second step and is regenerated in the seventh step. 


Examine the illustration carefully. It shows starting compounds (pyruvic acid and citric acid), intermediary carbon compounds (in notation form), waste products given off (carbon dioxide escaping to the outside), and energy-potential products (hydrogen atoms shown in the center of the illustration). 

 Now that you have completed your "road map"  for the reactions which occur in the Krebs Cycle, determine what goes into and out of the input/output box. This is the material you will be evaluated on during testing. 

                                                input/output box 
                                      (write in your notes and learn) 

   Organic Molecules -   Input: pyruvic acid   Output: 3 carbon dioxide  
                                     molecules and 2 waters per pyruvic acid  
    Energy Output - 
                   ATP ( 1 ATP per cycle formed directly by substrate phosphorylation) 
                   NADH (4 per cycle formed which may be converted into 3 ATP per 
                   NADH  thus a total of twelve ATP molecules may be formed by 
                   these coenzymes) 
                   FADH2   (1 formed which may be converted into 2 ATP per 
                   FADH2  thus a total of two ATP molecules may be formed by this 
                   coenzyme) 

Kreb cycle  produces  1 ATP directly, 12 through NADH, and 2 through FADH2 total of 15 ATP per Kreb cycle. There are two Kreb cycles per glucose, thus a total of 30 ATP may be produced by the Kreb cycle reactions per glucose of cellular respiration. 

Substrate phosphorylation refers to the ATP made directly from a substrate. 
Oxidative phosphorylation refers to the ATP synthesized through the NADH 
 or FADH2  utilizing the cytochrome electrons system (CETS). 
 
 

Summary

During the process of aerobic carbohydrate metabolism, glucose molecules are completely converted into carbon dioxide and water. Thirty-six ATP molecules are formed for each glucose molecule which is completely metabolized. Six of the ATP molecules are from glycolysis and thirty are from the two Krebs Cycle. 

If no oxygen is available to the cell, it can still process sugar molecules and derive some energy from them, but the process is not nearly so efficient as when oxygen is present. This process is called fermentation. The next web page presents the picture of the cytochrome system where NADH and FADH release energy to form  ATP. Oxygen will be used to combine with excess hydrogen ions formed during these reactions to form water. 
 

 
 
Measuring the Energy Yield

 When hydrogen atoms liberate the last bit of energy and join the oxygen atom, the oxidative respiration process is complete. One glucose molecule has yielded all its available energy to the cell in the process of respiration. 

The diagram below illustrates the overall energy extraction process. 

 

To help you better understand oxidative respiration and carbon, hydrate metabolism, it is necessary to do some more bookkeeping. Let's find out how much energy is liberated as one glucose molecule is oxidized to produce water and carbon dioxide. Here is a slightly more detailed account of carbohydrate metabolism. Look at the following diagram. 

 When pyruvic acid goes through the Krebs cycle, how many hydrogen atoms linked to NAD and FAD  are liberated from the molecules? 

a. four 
b. eight 
c. twelve 
 Each hydrogen atom that progresses down the respiratory chain produces enough energy to drive the production of an average of three ATP molecules. 

A total of twelve hydrogen atoms pass down the respiratory chain and produce a total of thirty-six ATP molecules of stored energy. 

 The total number of ATP's produced from the breakdown of one sugar molecule is (click one): 

a. two 
b. thirty-six 
c. thirty-eight
This is the end of  lesson six . Click here to go back to the home page and lesson seven Respiration- Cytochrome Electron Transport System .    click 
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Last modified October 29, 1997.