Cellular respiration

All organisms use energy to carry out the functions of life. Some organisms obtain this energy directly from sunlight. Our cells obtain it by catabolizing complex organic molecules. Food contains carbohydrates, proteins and fats, all of which are rich in energy. The process of extracting that energy is called cellular respiration. Cellular respiration is a catabolic reaction that releases chemical bond energy of organic molecules as ATP and heat. There are two ways to extract ATP; aerobic and anaerobic respiration. Aerobic respiration is more efficient and produces more ATP.

Aerobic respiration
Aerobic respiration is a kind of catabolism in which the energy of organic molecules is released by using oxygen. It involves the ETS in which molecular oxygen is the final electron acceptor. Most eukaryotes and prokaryotes use aerobic respiration to obtain energy from glucose. C6H12O6 + 6O2 6CO2 + 6H2O + Energy The energy stored within a glucose molecule is yielded step by step in a series of reactions. If it was released all at once the generated heat would destroy the cell. The stages are:

Glycolysis (Cytoplasm) Pyruvate oxidation (Mitochondria) Krebs cycle (Matrix of mitochondria) ETS (Inner mitochondrial membrane)

Glycolysis
Glycolysis is a series of enzyme-catalyzed reactions initiated by the activation of a hexose molecule and terminating in the production of two molecules of pyruvate. The energy released during these reactions is stored in the form of ATP. It was discovered by Hans and Eduard Buchner. It consists of the preparatory phase and the payoff phase.

Preparatory phase
The preparatory phase activates the hexose sugar. It requires two molecules of ATP and has five distinctive stages. By the end of the phase two ATP molecules have been consumed and 2 PGAL molecules have been produced from a single glucose molecule. Phosphorylation of glucose In this stage a phosphate group is added to the last carbon of glucose by hexokinase which converts the molecule int o glucose-6-phosphate. Conversion of glucose-6-phosphate to fructose-6-phosphate Glucose-6-phosphate is converted into fructose-6-phosphate by the enzyme phosphohexose isomerase. Phosphorylation of fructose-6-phosphate to fructose 1, 6diphosphate Fructose-6-phosphate is phosphorylated by the addition of a second phosphate group to the first carbon by the enzyme

phosphofructokinase. This reaction consumes another ATP molecule. Cleavage of fructose-1, 6-diphosphate Fructose 1, 6-diphosphate is cleaved by the enzyme aldase to produce two molecules containing three carbons and one phosphate. One is PGAL and the other is dihydroxyacetone phosphate (DHAP). Conversion of dihydroxyacetone phosphate Dihydroxyacetone phosphate is converted into PGAL by the enzyme triose phosphate isomerase.

Payoff phase
The PGAL molecules enter the energy-payoff phase. Chemical bonds are broken and NAD+ picks up the electrons and H+ forming NADH. The released energy produces ATP. This way of making ATP is called substrate-level phosphorylation. During the payoff phase a small amount of energy is released and converted to ATP in five stages. Oxidation of PGAL to 1, 3-Diphosphoglycerate PGAL is converted into 1, 3-diphosphoglycerate by adding an inorganic phosphate and removing a hydrogen ion. ATP is not the source of the phosphate. The removed hydrogen molecules are accepted by NAD and 2 molecules of NADH + H+ are synthesized. The reaction is controlled by the enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Synthesis of ATP from 1, 3-diphosphoglycerate The phosphate on the first carbon is transferred to ADP by the enzyme phosphoglycerate kinase (PGK). Thus we get two molecules of ATP from one hexose sugar and were left with 3-phosphoglycerate (PGA). Conversion of PGA to 2-phosphoglycerate The enzyme phosphoglycerate mutase (PGM) transfers the phosphate group from the third to the second carbon. We now have two 2phosphoglycerate molecules. Removal of water from 2-phosphoglycerate Two water molecules are synthesized from two phosphoglycerate molecules by the enzyme enolase which leaves us with two molecules of phosphoenol pyruvate (PEP). Synthesis of ATP from PEP The remaining phosphate groups are transferred to ADP by pyruvate kinase and 2 ATP molecules are synthesized. The end product is pyruvate and its a substrate for pathways that follow.

As a result of glycolysis 2 ATP molecules are used to activate glucose, 2 molecules of NAD+ are reduced to obtain NADH + H+ and 4 molecules of ATP are synthesized. In total 2 molecules of ATP and 2 of NADPH + H+ are produced.

Pyruvate oxidation
The pyruvate produced in glycolysis diffuses across the double membrane of a mitochondrion and enters the mitochondrial matrix. Under aerobic conditions pyruvate is converted into acetyl CoA in a process that yields NADH + H+ and CO2. The produced acetyl CoA enters the Krebs cycle in the mitochondria.

Krebs cycle
The Krebs cycle is a series of biochemical reactions by which the acetyl portion of acetyl-CoA is degraded to carbon dioxide and water with the release of metabolic energy which is used to produce ATP. It occurs in the matrix of the mitochondria because the enzymes it requires are anchored on the inner membrane and the matrix of mitochondria. The cycle starts by the fusion of acetyl CoA and acetate which form citrate. This part of the cycle is the reason why the Krebs cycle is also called the Citric acid cycle. The citrate is then isomerized into isocitrate and then oxidized and decarboxylated to form -ketoglutarate, yielding NADH + H+ and CO2 in the process. The -ketoglutarate is then converted into succinate in a process that yields NADH + H+, a molecule of ATP and CO2. Succinate is converted into fumarate and a molecule of FADH2 is produced. The addition of water to fumarate produces malate and a molecule of NADH + H+.

Finally malate is converted to oxaloacetate yielding a molecule of NADH + H+. The cycle can now begin again with the condensation of oxaloacetate and acetyl coenzyme A. In a complete cycle, 3 molecules of NADH + H+, 1 molecule of FADH2, 1 ATP and 2 CO2 are produced. NADH + H+ release energy in the ETS and CO2 is removed from the cell. A single molecule completes the cycle two times.

ETC and chemiosmosis

The ETC is the final stage of aerobic respiration. In eukaryotic cells the electron transport chain lies in the inner membrane of the mitochondrion. In prokaryotes it lines the cell membrane. The electron transport chain is a series of electron carriers in the membrane of the mitochondria. Through a series of reactions electrons are passed to oxygen. That way we produce gradient and ultimately ATP. Because oxygen gains the electrons, electron transport needs it to be completed.

Oxidative phosphorylation
ATP synthesis is called phosphorylation. Oxidative phosphorylation is the synthesis of ATP by the transfer of electrons through the ETS to oxygen. The energized electrons are released during glycolysis and the Krebs cycle and are transported through the ETS In the form of NADH + H+ or FADH2. The ETC doesnt generate ATP. It only breaks the large energy drop from food to oxygen into smaller steps. To do this the ETC passes the electrons along a series of molecules which make them lose some of their energy. The lost energy is used to pump protons of H atoms to the other side of the mitochondrial membrane. The concentration gradient of protons drives the synthesis of ATP by chemiosmosis. We have the ATP synthase enzyme which is located in the inner mitochondrial membrane. It makes ATP from ADP as protons move into the mitochondrial matrix.

Calculation of ATP production and efficiency of respiration

Glycolysis gives us 2 ATP and 2 NADH + H+. The 2 NADH + H+ are used by the ETS to produce 4 ATP. During this stage NADH + H+ loses some of its energy so we get 2 ATP molecules instead of 3. In total we get 6 ATP. We get 2 more NADH + H+ from the conversion of pyruvate to acetyl CoA which are also used by the ETS and give us 6 ATP. The Krebs cycle gives us 6 NADH + H+ , 2FADH2 and 2 ATP. In total it generates 24 ATP. When we sum all that up we get a total of 36-38 ATP. The efficiency of aerobic respiration is about 40%.

Catabolism of lipids
The ultimate source of energy in living things are carbohydrates as theyre simple and usable without major modifications to their structure. Lipids and proteins can be used in energy production as a secondary source. However proteins are only used in emergencies since they are the structural components of the cells. The potential of a lipid molecule is higher than the potential energy of a carbohydrate molecule. However it can only be extracted after the cell has expended energy to break it down into a usable form. A lipid molecule is composed of a glycerol molecule and fatty acid chains. Before the catabolism it must be hydrolyzed into those components. After that the glycerol is converted into PGAL and transported into the glycolysis pathway to participate in the Krebs cycle. The fatty acid components must be degraded first. It reacts with acetyl CoA to form acyl CoA. A fatty acid composed of 16 carbons produces 8 acyl CoA molecules. During each reaction a molecule of water is added. During the .oxidation of a 16 C fatty acid 7 NADH + H+, 7 FADH2 and 8 acetyl CoA are synthesized. The CoA molecules participate in the Krebs cycle and release 24 NADH + H+, 8 FADH2 and 8 ATP. Totally 31 NADH + H+ and 15 FADH2 are produced. A lipid containing three fatty acid chains gives us 3 x 131 ATP plus the 19 ATP from glycerol which gives us 412 ATP molecules from a single lipid molecule.

Catabolism of proteins
In conditions where the human body has to cope with increased demands for energy the catabolism of glucose and lipids may be insufficient. In such case the final fuel is protein. Using protein has the risk of damaging vital organs and processes and because of that proteins are used only as a last resort. To catabolize a protein its peptide bonds must be broken at specific points. This produces about twenty amino acids each with a specific radical group. Theres a different process of catabolism for each amino acid.

Anaerobic respiration
Anaerobic respiration releases the energy of organic molecules without oxygen. Organisms such as bacteria and fungi live in habitats where oxygen is absent. They can produce ATP in the absence of oxygen in a process called anaerobic respiration or fermentation.

Glycolysis
Glycolysis breaks down glucose into two pyruvate molecules. At the end of glycolysis 2 ATP and 2 NADH are released.

Fermentation
Pyruvate is a key substance which can be catabolized under either anaerobic or aerobic conditions. After glycolysis three different pathways are possible: alcoholic fermentation, lactic acid fermentation and pyruvate oxidation (only in aerobic conditions).

Alcoholic fermentation
Alcoholic fermentation occurs in the cytoplasm of some anaerobic bacteria, in fungi, algae and protozoa. In this pathway pyruvate is decarboxylated into acetaldehyde with the release of CO2. It is then reduced to ethanol by the enzyme alcohol dehydrogenase. Alcoholic fermentation is used in the production of alcoholic beverages. Yeast cells are used in baking to produce the carbon dioxide which causes dough to rise but the alcohol evaporates during baking.

Lactic acid fermentation

Pyruvate can also be catabolized by lactic acid under anaerobic conditions. Pyruvate is reduced to lactic acid by the enzyme lactate dehydrogenase. This pathway is used in the muscles of mammals when the demand for oxygen exceeds that of supply. In such cases glucose can be catabolized by fermentation and can produce energy without the need for oxygen. The disadvantage of this is the accumulation of lactic acid in the intercellular matrix, leading to muscle cramps. The condition is reversed when sufficient amount of oxygen becomes available. The accumulated lactic acid is converted first to pyruvate then acetyl CoA and finally enters the Krebs cycle. Rigor mortis occurs by the same mechanism. The end product of fermentation can be harmful for organisms. High concentrations of lactic acid in the blood stimulate the brain to feel tired which is why eating yogurt which contains lactic acid makes us feel sleepy.

Efficiency of fermentation
Fermentation is far less efficient than aerobic respiration. Its only 5.14% efficient.