Cellular Respiration

Lecture I:

Lecture II:

Reading: Campbell and Reece, 2002: Chapter 9 - Cellular Respiration

Student Objectives: As a result of this lecture and the assigned reading, you should understand the following:

Cell release chemical energy by means of an exergonic process called cellular respiration, the aerobic harvesting of energy from food molecules by cells.

Cellular respiration is the energy-releasing chemical breakdown of molecules and the storage of energy from that breakdown in a form the cell can use to perform work, i.e., ATP. Normally there is an oxidation of the organic molecule (e.g., glucose) causing the hydrogen atoms (electrons and their accompanying protons) to be removed from the carbon atoms and eventually combined with oxygen (which is thereby reduced). The electrons go from higher energy levels to lower energy levels, and energy is released. This energy is released over many steps as electrons move to successively lower energy levels. Some of that energy is lost as heat; a portion of that energy (40%) is captured in the terminal phosphate bonds of ATP.

The efficiency in living systems is due to the fact that energy release occurs over the course of a series of controlled reaction steps.

The harvesting of energy = the rearrangement of electrons in chemical bonds. The common theme is that a cell transfers energy from one molecule to another by coupling an exergonic reaction (energy-releasing) to an endergonic reaction (energy-storing). The energy released was stored in the specific arrangement of a molecule's covalent bonds, and the energy stored is in the new covalent bonds formed. In short, cellular respiration rearranges electrons in chemical bonds. These are redox reactions. Because an electron transfer requires both a donor and an acceptor, oxidation and reduction always go together. An electron leaves one molecule only when it contacts another molecule that attracts it more strongly.

In respiration, there are two main coenzymes derived from B complex vitamins. First is NAD⁺, which in part is derived from B₃, niacin. The second coenzyme is FAD (flavin adenine dinucleotide), which in part is derived from B₂, riboflavin.

Glucose supplies energy to form ATP by two related processes: 1) glycolysis and 2) cellular respiration. The products of glycolysis are reactants used in respiration.

Glycolysis

In glycolysis ("splitting of sugar"), the 6-carbon glucose molecule is split into two 3-carbon molecules, pyruvate. In the process (which includes 9 chemical steps), 4 hydrogen atoms (i.e., 4 electrons and 4 protons) are removed from the glucose molecule. The 4 electrons and 2 of the protons are accepted by 2 molecules of NAD⁺, while the other 2 protons remain is solution (i.e., H⁺ ions). The net energy harvested from these reactions is in the form of ATP and NADH.
The ATP produced in glycolysis is in the later steps of the pathway when the two phosphate groups of intermediate molecules are transferred to ADP molecules to form ATP. This production of ATP by the direct, enzyme-mediated transfer of a phosphate group from a substrate to ADP is by the mechanism called substrate phosphorylation. This is different from electron transport (oxidative) phosphorylation, which requires oxygen and a transport system.
The sum in glycolysis is the production of 4 ATP molecules from each molecule of glucose. Since 2 molecules were need for early steps, the net gain is 2 ATPs/molecule of glucose. However, there was also a gain of 2 molecules of NADH, which can be used to generate ATP in cellular respiration. Also, the pyruvate molecules still contain a large amount of the chemical energy of the original glucose molecule; this energy is extracted in cellular respiration.
Glycolysis occurs in the cytosol and does not require oxygen (i.e., it is an anaerobic process). In the presence of oxygen, the pyruvates are fed into the second stage of energy capturing, respiration. In the absence of oxygen, the pyruvate is converted to either lactic acid or ethanol. This conversion process is known as fermentation, and it produces no ATP. Fermentation is a way for cells to replenish the supply of NAD⁺ that the cell is using in glycolysis. While the low energy yield of 2 ATP for anaerobic glycolysis (5% of energy could harvest from glucose) may be enough for some single-celled organisms, it is not enough to sustain large multicellular organisms.

Respiration

Respiration occurs in two (2) stages: 1) the Krebs cycle (citric acid cycle) and 2) the terminal electron transport chain. In eukaryotes these reactions take place in mitochondria.

Some enzymes of the Krebs cycle are in the matrix of mitochondria; other enzymes of the Krebs cycle and the enzymes of the electron transport system are in the membrane of the cristae of the inner membrane. The outer membrane is relatively permeable, while the inner membrane restricts passage of most molecules and ions, including protons (H⁺ ions).

Compared to glycolysis, the Krebs cycle pays off big energy dividends to the cell. Each turn of the cycle makes 1 ATP molecule (by substrate level phosphorylation) and 4 other energy-rich molecules (3NADH and 1 FADH₂). Since two molecules of acetyl coA are processed for each glucose precursor, the total yield is 2ATP, 6NADH, and 2 FADH₂ (compared to the total of 2ATP and 2NADH molecules of glycolysis). No oxygen is required for the Krebs cycle.

After the Krebs cycle is completed, glucose is completely oxidized, but most of the energy is stored in electrons moved from carbon atoms to the electron carriers NAD⁺ and FAD. In terminal electron transport, the high energy electrons stored in the NADH and FADH₂ carriers are passed step-by-step to successively lower energy carriers embedded in the inner membrane of the mitochondrion until the electrons are finally accepted by the low energy level oxygen atom. As electrons are passed, the first carrier is oxidized and the acceptor carrier is reduced. The last molecule in the chain to receive electrons is oxygen. The oxygen and the accepted electrons combine with protons to produce water. The electrons keep moving in the transport chain because each carrier molecule has a greater affinity for electrons than its "uphill" neighbor. Remember, oxygen molecules are very electronegative and tend to pull electrons away from organic molecules. This process of producing ATP through the electron transport chain is termed oxidative phosphorylation.

Chemiosmotic Coupling. The theory of chemiosmotic coupling describes how cells use the potential energy in concentration gradients to make ATP. A concentration gradient of a solute stores energy due to the tendency of the solute molecules to diffuse from where they are more concentrated to where they are less concentrated. The theory of chemiosmotic coupling utilizes a gradient to generate energy to make ATP. ATP synthase synthesizes ATP using the energy stored in the concentration gradient of H⁺ ions (i.e., protons) across the inner membrane; which is relatively impermeable to H⁺. The H⁺ ions tend to move down their concentration gradient toward the matrix of the mitochondrion.

Cellular Respiration of Molecules other Than Glucose

Free glucose molecules is not common in our diet, so most of our calories (i.e., energy sources) come from fats, proteins, sucrose and starch.

Polysaccharides and disaccharides are broken down by enzymes into simple sugars that are funneled into glycolysis and the Krebs cycle.

Proteins are primarily broken down into amino acids to be used to make our own proteins, but cells can breakdown the amino acids to use as an energy source. Specific enzymes convert excess amino acids into other organic compounds. Depending on the specific amino acid and its breakdown products, the amino acids are converted into either pyruvate, acetyl coA, or one of the organic acids in the Krebs cycle.

Fats make excellent fuel because they contain may H atoms bound to carbons, and thus have many energy-rich electrons to be used to form ATP. The cell first hydrolyzes fats to glycerol and fatty acids. It then converts glycerol to glyceraldehyde 3-phosphate (G3P), one of the intermediates in glycolysis. The fatty acids are changed into acetyl coA, which then enters the Krebs cycle. Processed this way, one gram of fat yields more than twice as much ATP as one gram of starch, one of the reasons it is difficult for dieters to expend enough energy to burn off energy stored in each gram of fat.

Cellular Respiration in Prokaryotes

Mitochondria are not present in bacteria and cyanobacteria (blue-green algae). In these prokaryotic cells oxidative reactions are distributed between the cytoplasm and the plasma membrane.

The reactions of glycolysis follow essentially the same routes in prokaryotes and eukaryotes, except the products of fermentation are more varied under anaerobic conditions. Pyruvate oxidation and citric acid cycle also occur by the same pathways in prokaryotes and eukaryotes. However, in prokaryotes the enzymes and intermediates of the Krebs cycle are distributed throughout the cytoplasm. The pyruvate-dehydrogenase complex (catalyzes the conversion of pyruvate to acetyl CoA) and electron transport system are associated with the plasma membrane.

Some bacteria do not use organic molecules as the source of electrons. These bacteria can strip electrons directly from inorganic substances (such as H₂S, H₂, or Fe⁺⁺ - which also happens to be a prosthetic group in some electron carriers in the electron transport chain in eukaryotes). In this case, electrons are moved directly from the oxidized inorganic substances to the electron transport system with no intermediate steps.

In prokaryotes, the electron carriers are in complexes, similarly to carrier complexes in mitochondria. Most of the bacterial electron transport complexes are capable of pumping H⁺ as they cycle between oxidized and reduced states. The complexes move H⁺ from the cytoplasm to outside of the plasma membrane.

Aerobic species of prokaryotes use O₂ as the final acceptor of electrons.