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Cellular Respiration Introduction

What is Cellular Respiration?

Cellular respiration allows organisms to use (release) energy stored in the chemical bonds of glucose (C6H12O6). The energy in glucose is used to produce ATP. Cells use ATP to supply their energy needs. Cellular respiration is therefore a process in which the energy in glucose is transferred to ATP.

In respiration, glucose is oxidized and thus releases energy. Oxygen is reduced to form water. The carbon atoms of the sugar molecule are released as carbon dioxide (CO2). The complete breakdown of glucose to carbon dioxide and water requires two major steps: 1) glycolysis and 2) aerobic respiration. Glycolysis produces two ATP. Thirtyfour more ATP are produced by aerobic pathways if oxygen is present. In the absence of oxygen, fermentation reactions produce alcohol or lactic acid but no additional ATP.

Review of Electron Carriers

NAD+ + 2H p NADH + H+ FAD + 2H p FADH2

During glycolysis, glucose (C6) is broken down to two molecules of pyruvate (C3). (Note that compounds that end in "___ate" can be called "___ic acid". For example, lactate is lactic acid and malate is malic acid.) Glycolysis occurs in the cytoplasm (cytosol) and does not require oxygen. There are ten steps in glycolysis and each one is catalyzed by a specific enzyme. A brief summary of these reactions is presented here. 2 ATP molecules are used to phosphorylate and activate compounds that will eventually become converted to pyruvate (or pyruvic acid) (see diagram below). Two hydrogen atoms are removed by NAD+ forming 2 NADH (see diagram). Additional phosphorylation results in intermediate 3-carbon molecules with 2 phosphate groups. Four ATP are produced by substrate-level phosphorylation. Recall that substratelevel phosphorylation is the production of ATP using energy from other high-energy compounds but without the use of the electron transport system in the mitochondria.

The net yield of ATP in glycolysis is 2 for each glucose molecule (2 are used but 4 are produced).

Some bacteria have alternative energy-producing reactions. Two of these are the pentose phosphate pathway and the Entner-Doudoroff pathway.

Formation of Acetyl CoA

Pyruvate produced by glycolysis (see above) enters the mitochondrion and is converted to acetyl CoA by the reaction below. The remainder of the reactions of cellular respiration occur in the mitochondrion. pyruvate (C3) p acetyl CoA (C2) + CO2 During this step, NADH is produced from NAD+ + 2H (oxidation). This step must occur twice for each glucose molecule because each glucose molecule produces two pyruvate molecules in glycolysis (above). The two-carbon compound produced is attached to Coenzyme A to produce acetyl CoA.

Krebs Cycle
The Krebs cycle can be summarized by either of the diagrams below. The diagram below occurs twice, once for each acetyl CoA.

When acetyl CoA attaches to a C4 molecule in the Krebs cycle, the Coenzyme A is released. Two acetyl CoA molecules are consumed to produce 4 CO2, 2ATP, 6 NADH and 2 FADH2. The ATP molecules are produced by substrate-level phosphorylation. The diagram below also summarizes the Krebs Cycle.

Electron Transport and Oxidative Phosphorylation Mitochondrion structure

The inner membrane forms folds called cristae. These folds contain the carriers of the electron transport system. Acetyl CoA formation and the Krebs cycle occur in the inner space called the matrix. The space outside the inner membrane is the intermembrane space. The electron transport system pumps hydrogen ions (H+) into this space for oxidative phosphorylation.
Oxidative Phosphorylation

The electron transport system is found in the mitochondrion and chloroplast of eucaryotes and in the plasma membrane of procaryotes. It consists of a series of carrier molecules which pass electrons from a high-energy compound to a final lowenergy electron acceptor. Energy is released during these oxidation-reduction reactions to produce ATP. The discussion below applies to the mitochondria of eucaryotes. NADH or FADH2 bring electrons to the electron transport system in the mitochondria. The system contains membrane-bound electron carriers that pass electrons from one to another. When a carrier reduces another, some of the energy that is released as a result of that reduction is used to pump hydrogen ions across the membrane into the intermembrane space. The remaining energy is used to reduce the next carrier. As a result of the electron transport system, hydrogen ions become concentrated in the intermembrane space. These concentrated ions contain energy much like a dam. The enzyme ATP synthase is able to use the energy of this osmotic gradient to produce

ATP as the hydrogen ions move under osmotic pressure through the enzyme back into the matrix of the mitochondrion. Oxygen is the final electron acceptor. The low-energy electrons that emerge from the electron transport system are taken up by O2. The negatively charged oxygen molecules take up protons from the medium and form water (2H+ + 2e- + 1/2 O2 p H2O).

Summary of Glycolysis and Cellular Respiration


During glycolysis, glucose (C6) is converted to two pyruvates (C3). C-C-C-C-C-C p C-C-C + C-C-C
Formation of Acetyl CoA

One acetyl CoA is formed for each pyruvate produced by glycolysis (see the step above). C-C-C p C-C + CO2 pyruvate p acetyl CoA + CO2
Krebs Cycle

C-C p 2 CO2 The Krebs Cycle produces NADH, FADH2, and ATP. NADH and FADH2 carry electrons to the electron transport system.

Electron Transport System

In the electron transport system, NADH and FADH2 are oxidized and the energy is used to produce ATP.

Total ATP yield per glucose


NADH produced in the cytoplasm produces two to three ATP by the electron transport system. NADH produced in the mitochondria produces approximately three ATP. FADH2 adds its electrons to the electron transport system at a lower level than NADH, so it produces approximately two ATP.

2 ATP 2 NADH (= 4 ATP; these are converted to ATP in the mitochondria during cellular respiration)
Formation of Acetyl CoA

2 NADH (= 6ATP)
Krebs Cycle

6 NADH (= 18 ATP) 2 FADH2 (= 4 ATP) 2 ATP

Total Yield

Glycolysis produces 2 ATP; aerobic respiration produces 34 more ATP

Pathway Substrate-Level Oxidative Phosphorylation Phosphorylation Total ATP

Glycolysis CoA


2 NADH = 4 - 6 ATP 6 - 8 2 NADH = 6 ATP 6 NADH = 18 ATP 2 FADH2 = 4 ATP 6

Krebs Cycle





32 ATP

36 - 38

Without oxygen, cellular respiration could not occur because oxygen serves as the final electron acceptor in the electron transport system. The electron transport system would therefore not be available. Glycolysis can occur without oxygen. Although glycolysis does not require oxygen, it does require NAD+. Cells without oxygen available need to regenerate NAD+ from NADH so that in the absence of oxygen, at least some ATP can be made by glycolysis. To regenerate NAD+ from NADH, the electrons from NADH are added to pyruvate to produce alcohol (plants, yeast) or lactate (animals, bacteria). The total ATP yield of fermentation comes from glycolysis; 2 ATP molecules are produced per glucose.

Usefulness of Fermentation Anaerobic exercise

During vigorous exercise, oxygen is consumed faster than it is needed. Additional ATP energy is provided to the muscles by glycolysis and the result is a buildup of lactate in the muscles. When lactate builds up, the blood pH drops and the muscles fatigue. At rest, lactate is converted back to pyruvate (the oxygen debt is repaid). This is why you continue to breathe hard after you have finished running or rapid stair climbing.

Yeast produce alcohol which accumulates in their environment. As the concentration of alcohol in their environment increases, it becomes more and more toxic to them. Beer and wine have a maximum alcohol concentration because a higher concentration will kill the yeast cells.
Evolution of Cellular Respiration

Early cells probably fermented organic molecules in the oceans. Today, nearly all organisms show some form of fermentation which indicates that it evolved early in evolutionary history. Evolution typically operates by building upon or adding to what is already there. Aerobic respiration appears to have been added to fermentation.


Two ATP molecules are used to phosphorylate and activate glucose. Two hydrogen atoms are removed by NAD+ forming 2 NADH. Four ATP molecules are produced by substrate-level phosphorylation. The net yield of ATP is two; two are used and four are produced.


Fermentation is needed to regenerate NAD+ from NADH so that at least some ATP can be made in glycolysis. Electrons from NADH are added to pyruvate (reduction) to produce alcohol (plants, yeast) or lactate (animals, bacteria)
Aerobic Respiration

Aerobic respiration occurs when oxygen is available. pyruvate p CO2 + H2O It occurs in the mitochondrion. NAD+ and FAD carry electrons to the electron transport system. In the electron transport system, NADH and FADH2 are used to produce ATP as electrons are passed from one carrier to another. Eventually the electrons combine with hydrogen ions and oxygen (reduction) to form water.

Cellular Respiration Active Learning Exercise Study the questions below and try to answer them correctly based on the given notes. If the notes are inadequate to answer the questions, refer to other literature or references to get the correct answer. 1) What is the function of cellular respiration? 2) Describe how is ATP produced by substrate-level phosphorylation? 3) Describe how is ATP produced by chemiosmotic phosphorylation? 4) Glycolysis occurs in ______________ . (name the part of the cell) 5) How many ATP are produced and consumed during glycolysis? 6) How many NADH are produced by glycolysis? 7) During glycolysis, glucose is converted to _____ (how many?) ____________. (what?) 8) Tell how many carbon atoms are found in each of the two compounds that you named in the question above. 9) Explain why 2 pyruvates are formed from one glucose molecule instead of only one pyruvate. 10) Name the organelle where aerobic respiration occurs? 11) During aerobic respiration, carbon dioxide (CO2) is removed from each pyruvate and then coenzyme A is added. This forms ____________. 12) How many NADH molecules are produced for each acetyl CoA during the step described in the previous question? 13) For each molecule of glucose that begins cellular respiration, _____ molecules of acetyl CoA are produced. 14) During the Krebs cycle (also called the citric acid cycle), each acetyl CoA is broken down and the carbon is released as _______ (name the molecule). 15) The process listed in the step above produces _____ (how many) ATP, _____ (how many) NADH, and _____ (how many) FADH2 for each acetyl CoA. 16) For each molecule of glucose that enters cellular respiration, the number of ATP, NADH, and FADH2 produced by the Krebs cycle is _____, _____, and _____. The answer to this question can be found by multiplying your answers to question 15 by your answer to question 13. 17) For each molecule of glucose that enters cellular respiration, how many Carbon dioxide molecules (CO2) are produced?

18) In animals, what happens to the CO2`produced during cellular respiration? 19) Where does the electron transport system get the energy needed to pump hydrogen ions (protons) into the intermembrane space? 20) The final electron acceptor in cellular respiration is __________. 21) Each NADH produced during glycolysis contains enough energy to produce _____ (how many) ATP. This type of phosphorylation is called __________ ___________ phosphorylation. (2 words) 22) Each NADH produced during the formation of acetyl CoA and during the Krebs cycle contains enough energy to produce _____ (how many) ATP. 23) If there were no oxygen, fermentation enables glycolysis to occur but not __________ respiration. As a result, a total of _____ (how many) ATP are produced for each molecule of glucose. 24) If there were no oxygen and if fermentation did not occur, the cell would run out of __________ and glycolysis would stop. 25) The purpose of the reactions of fermentation are therefore to replenish the supply of __________ so that glycolysis can continue and produce ATP.

26) Glycolysis leads to the production of ____________ and two molecules of ATP.

In the absence of oxygen, fermentation leads to the production of ______________. Glycolysis plus the citric acid cycle can convert the carbons of glucose to _________ , storing the energy as ATP, _____________ and ___________.
A. lactic acid, pyruvate, CO2, NADH, FADH2 B. pyruvate, lactic acid, CO2, NADH, FADH2 C. CO2, NADH, FADH2, lactic acid, pyruvate D. O2, lactic acid, pyruvate, FADH2 E. glucose, lactic acid, CO2, NADH, FADH2

27.) At the end of glycolysis, each molecule of glucose has yielded 2 molecules of

_______, 2 molecules of ________, and a net of 2 molecules of _________.

A. FAD; NAD+; ADP B. CO2; NAD+; ADP C. lactic acid; ethanol; CO2 D. pyruvate, NADH, ATP E. H2O; CO2; ATP

28). Trematol is a metabolic poison derived from the white snake root. Cows eating

this plant concentrate the poison in their milk. The poison inhibits liver enzymes that convert lactic acid to other compounds for metabolism. Why does physical exertion increase symptoms of poisoning by trematol? Why does the pH of the blood decrease in a person who has digested trematol?
A. Physical exertion would increase the production of latic acid by fermentation, and the build up of lactic acid decreases blood pH when liver enzymes are blocked. B. Physical exertion increases metabolism, and the electron transport chain pumping H+ out of mitochondria increases blood pH.

29). Explain why in anaerobic cells the ratio of pyruvate/ lactate is much less than 1

while under aerobic conditions the ratio of pyruvate/ lactate is much greater than 1.
A. lactate is produced from pyruvate only under anaerobic conditions B. under anaerobic conditions pyruvate is converted to carbon dioxide C. in anaerobic conditions, pyruvate is converted to glucose using the energy of light D. lactate is the terminal electron acceptor under aerobic conditions E. pyruvate is transported into mitochondria under anaerobic conditions

30). The electron transport chain is located predominantly in the:

A. Outer membrane of the mitochondria B. Intermembrane space of the mitochondria C. Inner membrane of the mitochondria D. Matrix of the mitochondria E. Cytoplasm of the cell

31). In the first step of glycolysis, the enzyme hexokinase uses ATP to transfer a

phosphate to glucose to form glucose-6-phosphate. The product continues to be oxidized forming pyryvate in glycolysis and is a precursor to acetyl-CoA for the citric acid cycle. Suppose that a cell has only glucose available for energy and that the activity of hexokinase is suddenly stopped in this cell. Which of the following conditions will occur?

A. The cell will continue to produce energy from mitochondrial electron transport. B. The cell will continue to produce ATP using the citric acid cycle. C. The cell will ultimately be unable to produce ATP. D. The cell will be forced to switch to fermentation to produce ATP. E. The use of oxygen by the cell will increase.

32). During a heart attack, blood flowing to the heart muscle is interrupted by

blockage of a coronary artery. How would you expect the metabolism in the heart to change? A. oxidative phosphorylation would slow down in the mitochondria B. the rate of production of lactic acid would be stimulated C. the use of glucose by the muscle tissue would increase D. the production of water by mitochondria would be inhibited E. all are expected metabolic changes

33). ATP synthase can produce ATP using as a direct energy source:

A. energy from the conversion of glucose to pyruvate B. energy from the oxidation of pyruvate producing CO2 and H20 C. energy from a proton gradient established in mitochondria D. energy derived from the breakdown of NADH and FADH2 E. energy from the metabolism of amino acids

34). The terminal electron acceptor during mitochondrial respiration:

A. H20 B. NAD+ C. FAD D. ATP E. O2

35). As a result of glycolysis, pyruvate oxidation and the citric acid cycle, only a small

portion of the energy of glucose has been converted to ATP. At this point, the majority of the usable energy is contained in:
A. oxidized electron carriers NAD+ and FAD B. carbon dioxide C. pyruvate D. acetyl coenzyme A E. reduced electron carriers NADH and FADH