Cellular Respiration:  Using Energy From Food to make ATP

I.        All organisms use carbohydrate molecules as a primary energy source that is broken down to provide the energy to make ATP molecules.

A.   ATP then is used to provide the energy cells used to do work.

B.   The energy content of glucose is too great to use in individual cellular reactions.

C.  ATP has the right amount of energy for cellular reactions, and enzymes are adapted to couple ATP breakdown with reactions that require energy.

D.  Cellular respiration is the link between energy captured by plants in photosynthesis and the energy used by both plants and animals.

E.   Cellular respiration produces the low-energy molecules carbon dioxide and water, which are the raw materials of photosynthesis.

II.       Overview of glucose metabolism

A.   Glucose is the primary carbohydrate broken down by cells to produce a constant supply of ATP molecules.

1.   Energy in the bonds is released slowly, in steps.

2.   A gradual buildup of ATP accompanies the gradual breakdown of glucose.

3.   Complete metabolism of one molecule of glucose to carbon dioxide and water produces a maximum yield of 36 ATP molecules, 39% of the energy that was in the glucose.

B.   Glycolysis and fermentation

1.   Glycolysis is the pathway that breaks down 6-carbon glucose into two 3-carbon pyruvate molecules.

a)   It occurs in the cytosol outside the mitochondria.

b)   It is anaerobic—doesn’t require oxygen.

c)   Oxidation by removal of hydrogen atoms occurs.

d)   Energy of oxidation is used to generate 2 ATP molecules.

2.   Pyruvate is a pivotal metabolite.

a)   An aerobic pathway is followed if oxygen is present.

b)   If oxygen is not present, fermentation occurs anaerobically.

3.   Fermentation includes glycolysis plus the reduction of pyruvate to alcohol or to lactate.

a)   Yeast cells produce alcohol.

b)   Muscle cells produce lactic acid without enough oxygen present, producing cramps.

4.   Comparison of glycolysis and fermentation

a)   Glycolysis—anaerobic in cytosol, breaks down glucose to pyruvate, net gain of 2 ATP per glucose molecule.

b)   Fermentation—anaerobic in cytosol, breaks down glucose to alcohol or lactate, net gain of 2 ATP per glucose molecule (and these two ATP came from glycolysis.)

C.  Glycolysis and cellular respiration are linked when oxygen is available.

1.   Cellular respiration is the complete breakdown of pyruvate to CO2 and water.

a)   It occurs in mitochondria after glycolysis.

b)   It requires oxygen—aerobic.

2.   Pyruvate from glycolysis enters a mitochondrion when oxygen is present.

3.   Pyruvate is converted to an acetyl group, which enters the Krebs cycle.

4.   The next step in cellular respiration is the electron transport system.

5.   The overall reaction of cellular respiration produces water and CO2 from glucose and oxygen.

6.   ATP is produced from the energy in chemical bonds of glucose.

7.   Oxidation of glucose occurs by removal of hydrogen atoms (in the form of electrons and hydrogen ions) from metabolites, carried by coenzymes NAD+ and FAD to the electron transport system, where they combine with oxygen to form water.

8.   Overview of cellular respiration

a)   It occurs in mitochondria.

b)   It is aerobic.

c)   It breaks pyruvate to acetyl group, Krebs cycle, electron transport system.

d)   The final products are CO2 and H2O.

e)   There is a gain of 34 ATP per glucose molecule from these reactions.

9.   Total gain of ATP is 2 from glycolysis and 34 from cellular respiration for 36 ATP.

III.      Glycolysis chemical reactions

A.   Glucose is broken to 2 molecules of pyruvate.

1.   Two ATP molecules are broken to phosphorylate and activate metabolites.

2.   Hydrogen atoms are removed as electrons and hydrogen ions and picked up by NAD+, forming 2 NADH.

3.   High-energy phosphate bonds are used to make 4 ATP molecules, giving a net gain of 2 ATP molecules by substrate-level phosphorylation, where other molecules transfer their high-energy phosphates to ADP to make ATP.

4.   The end product of glycolysis is two 3-carbon pyruvates.

B.   Fermentation includes glycolysis plus reduction of pyruvate to either lactate or alcohol.

1.   Pyruvate accepts the 2 hydrogen atoms removed from glycolytic metabolites earlier.

2.   The end products in the most familiar kinds of fermentation are lactate (in many bacteria and animal cells) or ethyl alcohol and carbon dioxide (in yeasts and plant cells).

3.   The purpose of fermentation is to allow glycolysis to continue under anaerobic conditions so that ATP can be produced by providing a source of “free” NAD+ to pick up hydrogen ions.

4.   The energy yield of fermentation is 2 ATP molecules, each containing a high-energy phosphate bond with 7.3 Kcal of energy, for a total energy yield of 14.6 Kcal.

a)   Complete glucose breakdown to CO2 and H2O gives an energy yield of 686 Kcal.

b)   Energy yield from glycolysis is only 2.1% of that from complete glucose breakdown.

5.   The usefulness of fermentation is that it can provide a rapid burst of ATP energy.

a)   As muscles run out of oxygen, lactate fermentation continues to provide ATP energy anaerobically.

b)   As lactate builds up, the pH changes and muscles become fatigued.

c)   At rest after strenuous muscle activity, lactate must be converted back to pyruvate as the oxygen debt is repaid through breathing heavily.

d)   Yeast cells can also grow and divide for a while under anaerobic conditions through fermentation.

(1)  They are eventually killed by the alcohol they produce.

(2)  Alcoholic beverages and bread are produced through yeast fermentation that yields alcohol and carbon dioxide.

C.  Evolutionary perspective

1.   Fermentation has probably been present about as long as living things have been present on earth.

2.   Early cells probably fermented organic molecules present in the oceans.

3.   Some form of fermentation is still present in nearly all organisms, showing how important it must have been in ancestral cells.

4.   Since fermentation is so inefficient compared to aerobic respiration, it might be expected to have disappeared, but evolution has built on what was present before, and glycolysis has been continued as a part of the preliminary steps to aerobic respiration as well as part of fermentation.

IV.     Cellular respiration is aerobic respiration that occurs in mitochondria and uses oxygen as the final electron acceptor.

A.   There are 3 different levels in cellular respiration: the transition reaction that oxidizes pyruvate to an acetyl group, the Krebs cycle, and an electron transport system.

B.   The transition reaction connects glycolysis to the Krebs cycle.

1.   Pyruvate (C3) is oxidized and broken down to an acetyl group (C2) and CO2.

2.   The acetyl group is transferred to coenzyme A (CoA) to form acetyl CoA, which contains a high-energy bond.

3.   Oxidation of pyruvate forms a molecule of NADH.

4.   This transition reaction occurs twice for each glucose molecule, once for each of the 2 pyruvates formed by glycolysis.

C.  The Krebs cycle is a cyclic metabolic pathway in the matrix of the mitochondria.

1.   The acetyl CoA from the transition reaction enters the Krebs cycle to form the C6 molecule, citrate, giving the pathway the alternate name of the citric acid cycle.

2.   The C2 molecule that enters the pathway is oxidized to 2 CO2 molecules.

3.   During oxidation, most of the hydrogen atoms are donated to NAD+, but in one place they are donated to FAD.

4.   Some of the energy of oxidation is used to make ATP directly by substrate-level phosphorylation, as happens in glycolysis.

5.   The Krebs cycle turns twice for each glucose, once with each acetyl CoA entry.

D.  The electron transport system is located on the cristae of the mitochondria.

1.   Electrons are brought into this system from glycolysis and the Krebs cycle by NADH and FADH2.

2.   Some electron carriers of the system are cytochromes, so it is also called the cytochrome system.

3.   High-energy electrons enter the system, and low-energy electrons leave.

a)   The energy is transferred to the ATP molecules that are formed at 3 different sites along the system.

b)   This process is sometimes called oxidative phosphorylation because oxygen is the final electron acceptor for the low-energy electrons from the last of the carrier molecules.

c)   The enzyme cytochrome oxidase splits apart molecules of oxygen (O2) and reduces the oxygen to form water.

4.   Recycling of NAD+ and FAD involves continual reduction and oxidation, so only a limited supply of these coenzymes is present within the cell.

5.   Chemiosmotic ATP synthesis couples the energy released by the movement of electrons through the electron transport system to the production of energy-carrying ATP molecules.

a)   This coupling is only possible because of mitochondrial structure.

b)   The inner mitochondrial membrane forms cristae, projections into the matrix, and the carriers of the electron transport system are located in these membranes.

c)   The inner space within the cristae is filled with a gel-like substance, the matrix, where the transition reaction and the Krebs cycle occur.

d)   Some carriers of the electron transport system pump hydrogen ions into the intermembrane space between the inner and outer mitochondrial membranes, forming an extreme electrochemical gradient across the inner membrane.

e)   Reduction of oxygen to water removes hydrogen ions from the matrix and increases the gradient.

f)    ATP is synthesized as hydrogen ions flow out of the intermembrane space into the matrix through a channel protein in the ATP synthetase complex in the membrane, allowing chemiosmotic ATP synthesis as in the thylakoid membranes of chloroplasts.

V.      Energy yield from glucose metabolism

A.   Substrate-level phosphorylation produces 2 ATP molecules during glycolysis and 2 ATP molecules during the Krebs cycle, for a net yield of 4 ATP molecules.

B.   Oxidative phosphorylation produces many more ATP molecules.

1.   Each glucose produces 10 NADH and 2 FADH2 molecules that carry hydrogens to the electron transport chain.

2.   Each molecule of NADH produced inside the mitochondria by the Krebs cycle in turn produced 3 ATP molecules by electron transport.

3.   Each molecule of FADH2 yields 2 ATP molecules by electron transport.

4.   Hydrogens of NADH produced outside the mitochondria must be shuttled across the outer membrane, which usually causes them to be delivered to FAD, so they only produce 2 ATP molecules by electron transport.

C.  Efficiency of energy transformation

1.   About 39-40% of the energy available in glucose is present in the ATP molecules made by complete oxidation of glucose.

2.   The rest is lost in the form of heat, which is used by birds and mammals to maintain their body temperatures above the environmental temperature.

3.   Other organisms, including plants, cannot regulate their temperature and lose heat.

VI.     The metabolic pool and biosynthesis

A.   The primary organic compounds of cells can be oxidized and broken down for use in ATP generation or in synthetic reactions to build up new molecules.

B.   Energy can be released by degrading other compounds besides glucose.

1.   A fat is oxidized to 3 fatty acids and a glycerol molecule.

a)   Glycerol breaks down to PGAL, which enters glycolysis.

b)   Fatty acids are broken into acetyl groups, which enter the Krebs cycle.

c)   Fats are very efficient energy storage molecules, since they have 3 fatty acid chains and a fatty acid with 18 carbons can produce 108 ATP molecules.

2.   The energy yield of proteins is equivalent to carbohydrates.

a)   Proteins are broken into amino acids, which are deaminated with removal of the amino group, which is excreted.

b)   The number of carbons left in the carbon determines where it enters the Krebs cycle.

C.  Substrates in the pathways of glycolysis and cellular respiration can be used as starting points for synthesis reactions.

1.   These form the cell’s metabolic pool, from which one molecule can be converted to another.

2.   PGAL can be converted to glycerol, and acetyl groups to fatty acids, to make fats.

3.   Some metabolites can be converted to amino acids for protein synthesis.

a)   Plants can synthesize all the amino acids they require.

b)   Animals lack enzymes to make some amino acids, so these essential amino acids must be obtained from the diet.

4.   Other degradative pathways are also able to supply biosynthetic substrates, such as the pentose phosphate shunt, which converts glucose to pentose sugars rather than to pyruvate (important in nucleotide formation).