Cells obtain energy for their metabolic reactions from breaking down organic molecules with a high energy content. This energy is mostly stored as ATP molecules.
The process of obtaining energy in order to produce ATP molecules is called cellular respiration.
ATP, or adenosine triphosphate, is formed after the binding of one phosphate molecule (phosphorylation) to one ADP (adenosine diphosphate) molecule. This is a process that stores energy in the produced ATP molecule.
When ATP provides energy to the cellular metabolism, it releases one of its phosphate ions and ADP reappears.
ADP can also release more phosphate ions and generate AMP (adenosine monophosphate) or even non-phosphorylated adenosine. Adenosine production from ATP is used in tissues that need an urgent supply oxygen, such as in the heart during a myocardial infarction (heart attack). This is because adenosine creates a local vasodilator effect, thus providing faster vasodilation than other physiological methods.
There are two types of cell respiration: aerobic cell respiration, a reaction with the participation of molecular oxygen (O₂); and anaerobic cell respiration, without the participation of molecular oxygen and which uses other inorganic molecules as an oxidant instead. There are several varieties of anaerobic cell respiration. The main one is fermentation.
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Some cells that usually obtain energy from aerobic cellular respiration can use fermentation when oxygen is not available.
There are bacteria and fungi that, in the absence of oxygen, use their anaerobic metabolic capability for energy supply. Muscle cells also use fermentation when oxygen is scarce.
Aerobic organisms are those whose cells do not survive without oxygen, since they depend on aerobic cell respiration to obtain energy for ATP production. Anaerobic organisms are those that live or can live in environments devoid of oxygen.
Facultative anaerobes, like the fungi Saccharomyces cerevisiae, a brewing yeast, can survive in oxygen-poor environments by using fermentation. However, when oxygen is available, these organisms use aerobic respiration.
Obligate anaerobes are those that cannot survive when oxygen is present. Some fungi, some bacteria (like the agent of botulism Clostridium botulinum, and the agent of tetanus, Clostridium tetani) and some protozoans are examples of obligate anaerobes.
The two main types of fermentation are alcoholic fermentation and lactic fermentation.
In alcoholic fermentation, pyruvic acid, an intermediate molecule, is converted into ethanol with the release of carbon dioxide. The equation for alcoholic fermentation is as follows:
C₆H₁₂O₆ + 2 ADP + P --> 2 C₂H₅OH + 2 CO₂ + 2 ATP
In lactic fermentation, pyruvic acid is transformed into lactic acid and there is no production of carbon dioxide. The equation for lactic fermentation is:
C₆H₁₂O₆ + 2 ADP + P --> 2 C₃H₅OOH + 2 ATP
In fermentation, glucose (sugar) is broken down into pyruvic acid (each glucose molecule forms two pyruvic acid molecules). In this process, two molecules of ATP are produced.
Depending on to the type of fermentation, pyruvic acid can produce ethanol and carbon dioxide (in alcoholic fermentation) or lactic acid (in lactic fermentation). There are other varieties of fermentation in which pyruvic acid can generate acetic acid (acetic fermentation), propionic acid, isopropanol (also a type of alcohol), etc. The type of fermentation depends on the species of the involved organisms.
Fermentation causes cakes and breads to grow. This is accomplished by the release of carbon dioxide in alcoholic fermentation, as the gas passes through the dough and makes it grow. In lactic fermentation, there is no release of carbon dioxide and the desired result would not be obtained.
Some bacteria ferment milk lactose via lactic fermentation, producing lactic acid. This product is responsible for the acidic flavor of yogurt, curds and milk.
A typical fermentation process due to oxygen scarcity happens in muscle tissue. Under intense use, muscles require too much energy (ATP) and consume much more oxygen to produce that energy. High consumption leads to oxygen scarcity and the muscle cells begin to use lactic fermentation to satisfy their energy needs. In this situation, muscle pain, cramps and fatigue are due to the lactic acid released by fermentation.
In fermentation, two ATP molecules are produced from one glucose molecule. In aerobic respiration, a much more productive process, 36 ATP molecules are made from one glucose molecule.
The cell organelles specialized in aerobic respiration are the mitochondria.
Mitochondria are organelles enclosed by two lipid membranes. The inner membrane invaginates to the interior of the organelle, forming cristae and delimiting an internal space known as the mitochondrial matrix.
The three phases of aerobic cell respiration are glycolysis, the Krebs cycle and the respiratory chain (also known as the electron transport chain).
Glycolysis, the first stage of aerobic cell respiration, is a process in which glucose is broken down to form two pyruvic acid molecules along with the formation of two ATP and two NADH molecules.
Glycolysis is a complex reaction that involves the formation of several intermediate molecules until pyruvic acid molecules are made. Although two ATP molecules are consumed in the reaction, four molecules of ATP are also produced; therefore, a positive balance of two ATP molecules is obtained. Two NADH molecules are also produced. In glycolysis, the 6-carbon structure of glucose is broken down and two organic chains of three carbons each are produced. These chains produce two pyruvic acid molecules.
Glycolysis happens in the cytosol and not within the mitochondria. Pyruvic acid molecules later enter the mitochondria to participate in the next phase of aerobic cell respiration.
Glycolysis is a process similar to the breaking down of glucose in fermentation. It produces (a final balance of) two molecules of ATP for each glucose broken down.
NAD (nicotinamide adenine dinucleotide) is a hydrogen acceptor and necessary reductant (to receive hydrogen) in some reactions, in which it is reduced and converted into NADH₂. During glycolysis, two NAD molecules gain hydrogen ions released after an intermediate reaction, thus forming NADH₂.
The pyruvic acid molecules made in the cytosol via glycolysis enter the mitochondria.
Within the mitochondria, each pyruvic acid molecule is converted into one molecule of acetyl-CoA (acetyl coenzyme A), releasing one carbon dioxide molecule. The Krebs Cycle (also known as the citric acid cycle), the second stage of aerobic respiration, then begins.
Pyruvic acid is 2-oxopropanoic acid. Therefore, it is composed of three linearly bound carbon atoms with one extremity forming the organic acid function (COOH) and the middle carbon atom binding to an oxygen atom by double bond.
Each glucose molecule “cycles” the Krebs cycle twice because, after glycolysis, each used glucose molecule has generated two pyruvic acid molecules and each pyruvic acid molecule is converted in a 1:1 proportion into acetyl CoA. Each acetyl CoA molecule then goes through a Krebs cycle.
The Krebs cycle is called the final common pathway of the breaking down of organic compounds because it is also possible to generate acetyl CoA from the breaking down of lipids and proteins. Since acetyl CoA is the substrate that triggers the Krebs cycle, this process is called the final common pathway because it is activated by other organic molecules (lipids and proteins) and not only by glucose.
The body uses its energy reserves of fat and protein to cycle the Krebs cycle when experiencing malnutrition or when there is no glucose available for the cells.
After each round of the Krebs cycle, two carbon dioxide molecules, eight protons (hydrogen ions) captured by NAD and FAD (also a hydrogen acceptor) and one ATP molecule are produced.
During the Krebs cycle, acetyl CoA is broken down. At the end, the useful energy is incorporated into hydrogen atoms transported by FADH₂ and NADH₂ molecules.
Each round of the Krebs cycle releases two carbon dioxide molecules.
At the end of the cycle, all carbon atoms from the original glucose molecule broken down during glycolysis are already released, incorporated in carbon dioxide molecules. That occurs because, for each glucose, two pyruvic acid molecules were made during glycolysis. Each of these two pyruvic acid molecules is then converted into acetyl CoA with the release of one carbon dioxide molecule (two in total). Since each of the two produced acetyl CoA molecules cycles the Krebs cycle once, the initial glucose molecule triggers two rounds of the Krebs cycle and, as a result, four other carbon dioxide molecules are produced.
All of the six carbons atoms of the glucose molecule are then incorporated into six carbon dioxide molecules (two made during acetyl CoA formation and four during the two cycles of the Krebs cycle).
The respiratory chain, or the electron transport chain, is performed by protein systems located in the inner membrane of the mitochondria. Energized electrons of hydrogen atoms transported by NADH₂ and FADH₂ are the products of the preceding phases which are used in the respiratory chain.
Cytochromes are proteins of the internal mitochondrial membrane that are specialized in electron transfer and which participate in the respiratory chain. Energized electrons released by the hydrogen donors NADH₂ and FADH₂ (then reconverted into NAD and FAD) pass through a sequence of cytochromes, losing energy each time. The energy is then used in the synthesis of ATP.
FADH₂ and NADH₂ are oxidized into FAD and NAD and release hydrogen ions and highly energized electrons at the beginning of the respiratory chain.
The energy lost by electrons passing through the cytochromes is used to pump protons (hydrogen ions) out of the inner mitochondrial membrane (to the region between the inner and the outer membranes of the mitochondrion). The concentration gradient of hydrogen between the inner and the outer spaces separated by the inner membrane forces protons (hydrogen ions) to return to the mitochondrial matrix (the region inside the inner membrane). However, that return is only possible if the hydrogen ions pass through an enzymatic complex called ATP synthetase, which is embedded in the inner membrane. During that passage, the ATP synthetase phosphorylates ADP and ATP molecules are produced.
Hydrogen released in the mitochondrion then bonds with oxygen to form water. As a reaction that depends on oxygen, this type of ATP synthesis is called oxidative phosphorylation.
Oxygen is involved in aerobic respiration in its final phase, the respiratory chain. It is of fundamental importance because it is responsible for the maintenance of the hydrogen concentration gradient between the spaces separated by the inner mitochondrial membrane. This gradient promotes the functioning of ATP synthetase and therefore the phosphorylation of ADP to form ATP. In the space inside the inner membrane, oxygen binds to free hydrogens atoms to form water. This hydrogen consumption maintains the hydrogen gradient and the traffic of protons through the ATP synthetase.
The entire aerobic respiration process takes place to make ATP synthetase work. Aerobic organisms, like us humans, for example, need to breathe oxygen to maintain the hydrogen concentration gradient and to keep ATP synthetase working.
Cyanide is a poison that inhibits the last cytochrome of the respiratory chain, interrupting ATP formation and thus causing the cell to die.
Anoxia is a situation in which there is no available oxygen in the cell. Without oxygen, the respiratory chain stops, there is no ATP production, the cell does not obtain energy and it dies.
Anoxia can be caused, for example, by pulmonary insufficiency (drowning, extensive pulmonary injuries, etc.), by obstructions, stoppages and deficiencies in tissue circulation (atherosclerosis of the coronary arteries that irrigate the myocardium, tourniquets, cardiac arrest), by hemolysis (lysis of red blood cell) or hemoglobin diseases (anemia, fetal erythroblastosis), etc.
After aerobic respiration, 38 ATP molecules are produced from the consumption of one glucose molecule (but two of these ATP molecules are consumed by glycolysis). The net gain of the process is then 36 ATP molecules per glucose molecule.
The general equation for aerobic respiration is:
C₆H₁₂O₆ + 6 O₂ + 36 ADP + 36 P --> 6 CO₂ + 6 H₂O + 36 ATP
The consumption of molecular oxygen (O₂) has a direct relationship with metabolic rate of aerobic cells and therefore the metabolic rate of organisms. Cells with a greater metabolic activity require more energy and this energy comes from ATP molecules. As ATP production is required, the intensity of aerobic cell respiration is also higher and more oxygen is consumed.
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