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Before reading this summary, review cellular respiration by watching this video (from Ricochet Science):

To watch this video on YouTube (and see closed captioning) - press the arrow icon in the bottom right corner of the video player.

This tutorial focused on the final steps of cellular respiration, the Krebs cycle and the Electron Transport Chain and chemiosmosis. Recall that at the end of glycolysis there is a net production of two molecules of ATP and two molecules of NADH. The ATP is produced via substrate-level phosphorylation; in this reaction, a phosphate group on an organic molecule is transferred directly (along with high-energy electrons) onto a molecule of ADP. Substrate-level phosphorylation also occurs once during the Krebs cycle.

For those organisms that completely oxidize glucose, the end product of glycolysis (pyruvate) is further oxidized by enzymes associated with the Krebs cycle (also known as the citric acid cycle and the tricarboxylic acid cycle or TCA cycle). In eukaryotes, the enzymes associated with the Krebs cycle are found in the mitochondria. Pyruvate moves into the mitochondria via specific carrier proteins located in the mitochondrial membranes (in prokaryotes, the Krebs cycle enzymes typically are not compartmentalized but are located in the same compartment as the glycolytic enzymes). Pyruvate is converted to acetyl CoA (accompanied by the evolution of CO2 and one molecule of NADH). The acetyl CoA then enters the Krebs cycle. Within the cell, the Krebs cycle organic acids are not arranged in a circle nor is there any circular arrangement of the enzymes. This pathway is termed a "cycle" (and diagrammed as a circle) because the end product becomes the first product after reacting with acetyl CoA. Acetyl CoA is not the only way that reduced carbon can enter the Krebs cycle. For example, the degradation products of some amino acids enter the Krebs cycle as organic acids (e.g., phenylalanine is converted to fumarate).

For every molecule of acetyl CoA that enters the cycle, there is a net gain of three molecules of NADH, one molecule of FADH2 (a chemical relative of NADH), and one molecule of ATP (the ATP is produced via substrate-level phosphorylation). Two molecules of CO2 are produced as a by-product. As with glycolysis, there is only a marginal gain of ATP; the majority of energy is tied up in the NADH and FADH2 molecules. How is this energy liberated? To answer this we need to consider the work that is done by NADH and FADH2 .

The high-energy carriers NADH and FADH2 can themselves be oxidized by the electron transport chain. During oxidation, energy is lost by the oxidized molecule while energy is gained by the reduced molecule. The electron transport chain is composed of a series of molecules that alternatively become oxidized and reduced by one another. As these redox reactions occur, free energy is made available to do work, and that work is the movement of charged hydrogen atoms (protons) across a membrane. The electron transport chain is mostly contained within the membrane, and energetically, the electrons that pass from one molecule to the next have decreasing potential energies. The last molecule that is reduced is oxygen, which results in the generation of water. Some bacteria can use other molecules (e.g., nitrate, sulfate, or organic acids) as terminal electron acceptors, and hence can undergo cellular respiration under anaerobic conditions.

So how is ATP produced? During the movement of electrons down the electron transport chain, protons accumulate on the other side of the inner mitochondrial membrane; mitochondria have a double membrane. The accumulation of charged ions, separated by a nonconductive membrane, creates a voltage. In other words, the mitochondrion can be thought of as a battery that is charged by the electron transport chain. Also existing within the inner membrane is a complex known as the ATP synthase complex. This complex acts as a channel in which protons flow back into the mitochondrion. As these protons move back into the mitochondria, free energy is released as the charge differential decreases; the resulting energy is used to synthesize ATP. In other words, the electron transport chain charges the battery, and the ATP synthase discharges it and uses the energy to produce ATP.

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