Linfei's Bio Blog: Cell Respiration

Cellular respiration allows organisms to use (release) energy stored in the chemical bonds of glucose. 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. Thirty-four 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.

Electron carriers:

NAD+ + 2H --> NADH + H+
FAD + 2H --> FADH2

I. Glycolysis:

During glycolysis, glucose (C6) is broken down to two molecules of pyruvate (C3).

Glycolysis occurs in the cytoplasm (cytosol) and does not require oxygen.

1) 2 ATP molecules are used to phosphorylate and activate compounds that will eventually become converted to pyruvate (or pyruvic acid).

2) Two hydrogen atoms are removed by NAD+ forming 2 NADH.

3) Additional phosphorylation results in intermediate 3-carbon molecules with 2 phosphate groups.

4) 4 ATP are produced by substrate-level phosphorylation. Recall that substrate-level 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.

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

II. Formation of Acetyl CoA(Coenzyme A)
Pyruvate produced by glycolysis enters the mitochondrion by active transport and is converted to acetyl CoA as shown below. The remainder of the reactions of cellular respiration occur in the mitochondrion.

pyruvate (C3) --> acetyl CoA (C2) + CO2

A carbon atom is removed from each of the pyruvate molecules forming a two-carbon compound and CO2. Each of the two-carbon compounds are oxidized forming NADH from NAD+. Coenzyme A is attached to each of the two-carbon compounds producing two acetyl CoA molecules.

III. Krebs Cycle

The Krebs Cycle is the central metabolic pathway in all aerobic organisms. The cycle is a series of eight reactions that occur in the mitochondrion. These reactions take a two carbon molecule (acetate) and completely oxidize it to carbon dioxide. The cycle is summarized in the following chemical equation:

acetyl CoA + 3 NAD + FAD + ADP + HPO₄^-2------> 2 CO₂ + CoA + 3 NADH⁺ + FADH⁺ + ATP

The Krebs Cycle is an aerobic process (one that requires oxygen) that produces ATP by breaking down glucose. The Krebs Cycle is not only part of the pathway for the breakdown of glucose, but also for the breakdown of all metabolites, including other sugars, amino acids and fatty acids. Each of these groups of molecules has a pathway that leads into the Krebs Cycle.

Steps in the Krebs Cycle:

1. The first reaction in the Krebs Cycle is the conversion of pyruvate to acetyl CoA. In this reaction, pyruvate, a three carbon molecule that is generated in glycolysis and in the metablism of some amino acids, is decarboxylated (a carboxyl group is removed) to the two carbon acetate. The carboxyl group is released as carbon dioxide. This reaction is catalyzed by the enzyme pyruvate dehydrogenase. This reaction is also an oxidation as 2 electrons are removed from pyruvate during the reaction. The two electrons are accepted by NAD and results in the formation of NADH. The oxidation of pyruvate is very exogonic. Some of the energy released from this reaction is transferred with the electrons to NADH and some is used to energize acetate by adding coenzyme A to acetate thus forming acetyl CoA, the actual product of the reaction.

substrates(reactants )	pyruvate	CoA + NAD
enzyme	pyruvate dehydrogenase
products	acetyl CoA	CO₂ + NADH

2. This reaction is a condensation reaction (a reaction that joins together two molecules) in which the 2-carbon acetate that was formed from pyruvate in the preceding reaction is attached to a 4-carbon molecule, oxaloacetate (OAA). The reaction creates the 6-carbon molecule (2 carbons from acetate and 4 from OAA) citrate. The joining of the acetate to OAA requires energy and this energy comes from the removal of the coenzyme A from the acetate.

substrates(reactants )	acetyl CoA + oxaloacetate
enzyme	citrate synthase
products	citrate (citric acid)	+ Co A

3. The next reaction is a rearrangement of citrate to isocitrate.

substrates(reactants )	citrate (citric acid)
enzyme	aconitase
products	isocitrate

4. In this reaction, isocitrate is oxidized to alpha ketoglutarate. Being an oxidation reaction, electrons are removed and are transferred, in this instance, to NAD to form NADH. In addition, this oxidation results in the release of carbon dioxide from isocitrate (see yellow atoms) so that the total number of carbons remaining is reduced by 1 to 5.

substrates(reactants )	isocitrate	+ NAD
enzyme	isocitrate dehydrogenase
products	alpha ketoglutarate	+ NADH + CO₂

5. In this reaction, the 5-carbon alpha ketoglutarate is converted into the 4-carbon succinate. This is an oxidation reaction (thus forming an NADH) that removes a carbon in the form of carbon dioxide. The remaining 4-carbon molecule will now be converted into oxaloacetate, the molecule that we needed to condense with acetyl CoA. The excess energy is conserved by the addition of Coenzyme A to the succinate thus forming succinyl CoA.

substrates(reactants )	alpha ketoglutarate	+ CoA + NAD
enzyme	alpha ketoglutarate dehydrogenase
products	succinly CoA	+ NADH + CO₂

6. In this reaction, the Coenzyme A is removed forming succinate. The energy that was stored in the linkage of the CoA to succinate is now used to attach a phosphate to GDP to form GTP. GTP is a close cousin to ATP and the cell has enzymes present that are capable of making an ATP from the energy in the GTP. This is not an oxidation reaction so no NADH is formed.

substrates(reactants )	succinyl CoA	+ ADP + PO₄
enzyme	succinyl CoA synthetase
products	succinate	+ CoA + ATP

7. This reaction is oxidation reaction, however, unlike the other oxidations that you have met in the cycle, no carbons are lost. In this instance, the succinate is oxidized to fumarate. Since it is an oxidation, electrons and energy are released. However, the amount of energy released in this reaction is not enough to drive the reduction of NAD to NADH and so FAD (flavin adenine dinucleotide) is used in this reaction - When FAD accepts electrons (and is therefore reduced), it becomes FADH.

substrates(reactants )	succinate	+ FAD
enzyme	succinate dehydrogenase
products	fumarate	+ FADH

8. This is a reaction that essentially rearranges the structure of fumrate into a molecule of malate.

substrates(reactants )	fumarate
enzyme	succinate dehydrogenase
products	malate

9. This is the 'last' reaction of the cycle. In this reaction, malate is oxidized to oxaloacetate. The electron acceptor for this reaction is NAD thus we form another NADH during this reaction. Since we have regenerated the OAA, all we need to begin another cycle is the addition of acetyl CoA.

substrates(reactants )	malate	+ NAD
enzyme	succinate dehydrogenase
products	oxaloacetate	+ NADH

IV. Electron Transport Chain

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 low-energy electron acceptor. Energy is released during these oxidation-reduction reactions to produce ATP. 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. The enzyme ATP synthaseis 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 --> H2O).