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Wednesday, April 3, 2024

Light-water reactor

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Light-water_reactor
A simple light-water reactor

The light-water reactor (LWR) is a type of thermal-neutron reactor that uses normal water, as opposed to heavy water, as both its coolant and neutron moderator; furthermore a solid form of fissile elements is used as fuel. Thermal-neutron reactors are the most common type of nuclear reactor, and light-water reactors are the most common type of thermal-neutron reactor.

There are three varieties of light-water reactors: the pressurized water reactor (PWR), the boiling water reactor (BWR), and (most designs of) the supercritical water reactor (SCWR).

History

Early concepts and experiments

After the discoveries of fission, moderation and of the theoretical possibility of a nuclear chain reaction, early experimental results rapidly showed that natural uranium could only undergo a sustained chain reaction using graphite or heavy water as a moderator. While the world's first reactors (CP-1, X10 etc.) were successfully reaching criticality, uranium enrichment began to develop from theoretical concept to practical applications in order to meet the goal of the Manhattan Project, to build a nuclear explosive.

In May 1944, the first grams of enriched uranium ever produced reached criticality in the low power (LOPO) reactor at Los Alamos, which was used to estimate the critical mass of U235 to produce the atomic bomb. LOPO cannot be considered as the first light-water reactor because its fuel was not a solid uranium compound cladded with corrosion-resistant material, but was composed of uranyl sulfate salt dissolved in water. It is however the first aqueous homogeneous reactor and the first reactor using enriched uranium as fuel and ordinary water as a moderator.

By the end of the war, following an idea of Alvin Weinberg, natural uranium fuel elements were arranged in a lattice in ordinary water at the top of the X10 reactor to evaluate the neutron multiplication factor. The purpose of this experiment was to determine the feasibility of a nuclear reactor using light water as a moderator and coolant, and clad solid uranium as fuel. The results showed that, with a lightly enriched uranium, criticality could be reached. This experiment was the first practical step toward the light-water reactor.

After World War II and with the availability of enriched uranium, new reactor concepts became feasible. In 1946, Eugene Wigner and Alvin Weinberg proposed and developed the concept of a reactor using enriched uranium as a fuel, and light water as a moderator and coolant. This concept was proposed for a reactor whose purpose was to test the behavior of materials under neutron flux. This reactor, the Material Testing Reactor (MTR), was built in Idaho at INL and reached criticality on March 31, 1952. For the design of this reactor, experiments were necessary, so a mock-up of the MTR was built at ORNL, to assess the hydraulic performances of the primary circuit and then to test its neutronic characteristics. This MTR mock-up, later called the Low Intensity Test Reactor (LITR), reached criticality on February 4, 1950 and was the world's first light-water reactor.

Pressurized water reactors

Immediately after the end of World War II the United States Navy started a program under the direction of Captain (later Admiral) Hyman Rickover, with the goal of nuclear propulsion for ships. It developed the first pressurized water reactors in the early 1950s, and led to the successful deployment of the first nuclear submarine, the USS Nautilus (SSN-571).

The Soviet Union independently developed a version of the PWR in the late 1950s, under the name of VVER. While functionally very similar to the American effort, it also has certain design distinctions from Western PWRs.

Boiling water reactor

Researcher Samuel Untermyer II led the effort to develop the BWR at the US National Reactor Testing Station (now the Idaho National Laboratory) in a series of tests called the BORAX experiments.

PIUS reactor

PIUS, standing for Process Inherent Ultimate Safety, was a Swedish design designed by ASEA-ATOM. It is a concept for a light-water reactor system. Along with the SECURE reactor, it relied on passive measures, not requiring operator actions or external energy supplies, to provide safe operation. No units were ever built.

OPEN100

In 2020, the Energy Impact Center announced publication of an open-sourced engineering design of a pressurized water reactor capable of producing 300 MWth/100 MWe of energy called OPEN100.

Overview

The Koeberg nuclear power station, consisting of two pressurized water reactors fueled with uranium

The family of nuclear reactors known as light-water reactors (LWR), cooled and moderated using ordinary water, tend to be simpler and cheaper to build than other types of nuclear reactors; due to these factors, they make up the vast majority of civil nuclear reactors and naval propulsion reactors in service throughout the world as of 2009. LWRs can be subdivided into three categories – pressurized water reactors (PWRs), boiling water reactors (BWRs), and supercritical water reactors (SCWRs). The SCWR remains hypothetical as of 2009; it is a Generation IV design that is still a light-water reactor, but it is only partially moderated by light water and exhibits certain characteristics of a fast neutron reactor.

The leaders in national experience with PWRs, offering reactors for export, are the United States (which offers the passively safe AP1000, a Westinghouse design, as well as several smaller, modular, passively safe PWRs, such as the Babcock & Wilcox MPower, and the NuScale MASLWR), the Russian Federation (offering both the VVER-1000 and the VVER-1200 for export), the Republic of France (offering the AREVA EPR for export), and Japan (offering the Mitsubishi Advanced Pressurized Water Reactor for export); in addition, both the People's Republic of China and the Republic of Korea are both noted to be rapidly ascending into the front rank of PWR-constructing nations as well, with the Chinese being engaged in a massive program of nuclear power expansion, and the Koreans currently designing and constructing their second generation of indigenous designs. The leaders in national experience with BWRs, offering reactors for export, are the United States and Japan, with the alliance of General Electric (of the US) and Hitachi (of Japan), offering both the Advanced Boiling Water Reactor (ABWR) and the Economic Simplified Boiling Water Reactor (ESBWR) for construction and export; in addition, Toshiba offers an ABWR variant for construction in Japan, as well. West Germany was also once a major player with BWRs. The other types of nuclear reactor in use for power generation are the heavy water moderated reactor, built by Canada (CANDU) and the Republic of India (AHWR), the advanced gas cooled reactor (AGCR), built by the United Kingdom, the liquid metal cooled reactor (LMFBR), built by the Russian Federation, the Republic of France, and Japan, and the graphite-moderated, water-cooled reactor (RBMK or LWGR), found exclusively within the Russian Federation and former Soviet states.

Though electricity generation capabilities are comparable between all these types of reactor, due to the aforementioned features, and the extensive experience with operations of the LWR, it is favored in the vast majority of new nuclear power plants. In addition, light-water reactors make up the vast majority of reactors that power naval nuclear-powered vessels. Four out of the five great powers with nuclear naval propulsion capacity use light-water reactors exclusively: the British Royal Navy, the Chinese People's Liberation Army Navy, the French Marine nationale, and the United States Navy. Only the Russian Federation's Navy has used a relative handful of liquid-metal cooled reactors in production vessels, specifically the Alfa class submarine, which used lead-bismuth eutectic as a reactor moderator and coolant, but the vast majority of Russian nuclear-powered boats and ships use light-water reactors exclusively. The reason for near exclusive LWR use aboard nuclear naval vessels is the level of inherent safety built into these types of reactors. Since light water is used as both a coolant and a neutron moderator in these reactors, if one of these reactors suffers damage due to military action, leading to a compromise of the reactor core's integrity, the resulting release of the light-water moderator will act to stop the nuclear reaction and shut the reactor down. This capability is known as a negative void coefficient of reactivity.

Currently offered LWRs include the following

LWR statistics

Data from the International Atomic Energy Agency in 2009:

Reactors in operation. 359
Reactors under construction. 27
Number of countries with LWRs. 27
Generating capacity (gigawatts). 328.4

Reactor design

The light-water reactor produces heat by controlled nuclear fission. The nuclear reactor core is the portion of a nuclear reactor where the nuclear reactions take place. It mainly consists of nuclear fuel and control elements. The pencil-thin nuclear fuel rods, each about 12 feet (3.7 m) long, are grouped by the hundreds in bundles called fuel assemblies. Inside each fuel rod, pellets of uranium, or more commonly uranium oxide, are stacked end to end. The control elements, called control rods, are filled with pellets of substances like hafnium or cadmium that readily capture neutrons. When the control rods are lowered into the core, they absorb neutrons, which thus cannot take part in the chain reaction. On the converse, when the control rods are lifted out of the way, more neutrons strike the fissile uranium-235 or plutonium-239 nuclei in nearby fuel rods, and the chain reaction intensifies. All of this is enclosed in a water-filled steel pressure vessel, called the reactor vessel.

In the boiling water reactor, the heat generated by fission turns the water into steam, which directly drives the power-generating turbines. But in the pressurized water reactor, the heat generated by fission is transferred to a secondary loop via a heat exchanger. Steam is produced in the secondary loop, and the secondary loop drives the power-generating turbines. In either case, after flowing through the turbines, the steam turns back into water in the condenser.

The water required to cool the condenser is taken from a nearby river or ocean. It is then pumped back into the river or ocean, in warmed condition. The heat can also be dissipated via a cooling tower into the atmosphere. The United States uses LWR reactors for electric power production, in comparison to the heavy water reactors used in Canada.

Control

A pressurized water reactor head, with the control rods visible on the top

Control rods are usually combined into control rod assemblies — typically 20 rods for a commercial pressurized water reactor assembly — and inserted into guide tubes within a fuel element. A control rod is removed from or inserted into the central core of a nuclear reactor in order to control the number of neutrons which will split further uranium atoms. This in turn affects the thermal power of the reactor, the amount of steam generated, and hence the electricity produced. The control rods are partially removed from the core to allow a chain reaction to occur. The number of control rods inserted and the distance by which they are inserted can be varied to control the reactivity of the reactor.

Usually there are also other means of controlling reactivity. In the PWR design a soluble neutron absorber, usually boric acid, is added to the reactor coolant allowing the complete extraction of the control rods during stationary power operation ensuring an even power and flux distribution over the entire core. Operators of the BWR design use the coolant flow through the core to control reactivity by varying the speed of the reactor recirculation pumps. An increase in the coolant flow through the core improves the removal of steam bubbles, thus increasing the density of the coolant/moderator with the result of increasing power.

Coolant

The light-water reactor also uses ordinary water to keep the reactor cooled. The cooling source, light water, is circulated past the reactor core to absorb the heat that it generates. The heat is carried away from the reactor and is then used to generate steam. Most reactor systems employ a cooling system that is physically separate from the water that will be boiled to produce pressurized steam for the turbines, like the pressurized-water reactor. But in some reactors the water for the steam turbines is boiled directly by the reactor core, for example the boiling-water reactor.

Many other reactors are also light-water cooled, notably the RBMK and some military plutonium-production reactors. These are not regarded as LWRs, as they are moderated by graphite, and as a result their nuclear characteristics are very different. Although the coolant flow rate in commercial PWRs is constant, it is not in nuclear reactors used on U.S. Navy ships.

Fuel

A nuclear fuel pellet
Nuclear fuel pellets that are ready for fuel assembly completion

The use of ordinary water makes it necessary to do a certain amount of enrichment of the uranium fuel before the necessary criticality of the reactor can be maintained. The light-water reactor uses uranium 235 as a fuel, enriched to approximately 3 percent. Although this is its major fuel, the uranium 238 atoms also contribute to the fission process by converting to plutonium 239; about one-half of which is consumed in the reactor. Light-water reactors are generally refueled every 12 to 18 months, at which time, about 25 percent of the fuel is replaced.

The enriched UF6 is converted into uranium dioxide powder that is then processed into pellet form. The pellets are then fired in a high-temperature, sintering furnace to create hard, ceramic pellets of enriched uranium. The cylindrical pellets then undergo a grinding process to achieve a uniform pellet size. The uranium oxide is dried before inserting into the tubes to try to eliminate moisture in the ceramic fuel that can lead to corrosion and hydrogen embrittlement. The pellets are stacked, according to each nuclear core's design specifications, into tubes of corrosion-resistant metal alloy. The tubes are sealed to contain the fuel pellets: these tubes are called fuel rods.

The finished fuel rods are grouped in special fuel assemblies that are then used to build up the nuclear fuel core of a power reactor. The metal used for the tubes depends on the design of the reactor – stainless steel was used in the past, but most reactors now use a zirconium alloy. For the most common types of reactors the tubes are assembled into bundles with the tubes spaced precise distances apart. These bundles are then given a unique identification number, which enables them to be tracked from manufacture through use and into disposal.

Pressurized water reactor fuel consists of cylindrical rods put into bundles. A uranium oxide ceramic is formed into pellets and inserted into zirconium alloy tubes that are bundled together. The zirconium alloy tubes are about 1 cm in diameter, and the fuel cladding gap is filled with helium gas to improve the conduction of heat from the fuel to the cladding. There are about 179-264 fuel rods per fuel bundle and about 121 to 193 fuel bundles are loaded into a reactor core. Generally, the fuel bundles consist of fuel rods bundled 14x14 to 17x17. PWR fuel bundles are about 4 meters in length. The zirconium alloy tubes are pressurized with helium to try to minimize pellet cladding interaction which can lead to fuel rod failure over long periods.

In boiling water reactors, the fuel is similar to PWR fuel except that the bundles are "canned"; that is, there is a thin tube surrounding each bundle. This is primarily done to prevent local density variations from affecting neutronics and thermal hydraulics of the nuclear core on a global scale. In modern BWR fuel bundles, there are either 91, 92, or 96 fuel rods per assembly depending on the manufacturer. A range between 368 assemblies for the smallest and 800 assemblies for the largest U.S. BWR forms the reactor core. Each BWR fuel rod is back filled with helium to a pressure of about three atmospheres (300 kPa).

Moderator

A neutron moderator is a medium which reduces the velocity of fast neutrons, thereby turning them into thermal neutrons capable of sustaining a nuclear chain reaction involving uranium-235. A good neutron moderator is a material full of atoms with light nuclei which do not easily absorb neutrons. The neutrons strike the nuclei and bounce off. After sufficient impacts, the velocity of the neutron will be comparable to the thermal velocities of the nuclei; this neutron is then called a thermal neutron.

The light-water reactor uses ordinary water, also called light water, as its neutron moderator. The light water absorbs too many neutrons to be used with unenriched natural uranium, and therefore uranium enrichment or nuclear reprocessing becomes necessary to operate such reactors, increasing overall costs. This differentiates it from a heavy water reactor, which uses heavy water as a neutron moderator. While ordinary water has some heavy water molecules in it, it is not enough to be important in most applications. In pressurized water reactors the coolant water is used as a moderator by letting the neutrons undergo multiple collisions with light hydrogen atoms in the water, losing speed in the process. This moderating of neutrons will happen more often when the water is denser, because more collisions will occur.

The use of water as a moderator is an important safety feature of PWRs, as any increase in temperature causes the water to expand and become less dense; thereby reducing the extent to which neutrons are slowed down and hence reducing the reactivity in the reactor. Therefore, if reactivity increases beyond normal, the reduced moderation of neutrons will cause the chain reaction to slow down, producing less heat. This property, known as the negative temperature coefficient of reactivity, makes PWRs very stable. In event of a loss-of-coolant accident, the moderator is also lost and the active fission reaction will stop. Heat is still produced after the chain reaction stops from the radioactive byproducts of fission, at about 5% of rated power. This "decay heat" will continue for 1 to 3 years after shut down, whereupon the reactor finally reaches "full cold shutdown". Decay heat, while dangerous and strong enough to melt the core, is not nearly as intense as an active fission reaction. During the post shutdown period the reactor requires cooling water to be pumped or the reactor will overheat. If the temperature exceeds 2200 °C, cooling water will break down into hydrogen and oxygen, which can form a (chemically) explosive mixture. Decay heat is a major risk factor in LWR safety record.

Malonyl-CoA decarboxylase

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Malonyl-CoA_decarboxylase

Malonyl-CoA decarboxylase (EC 4.1.1.9), (which can also be called MCD and malonyl-CoA carboxyl-lyase) is found in bacteria and humans and has important roles in regulating fatty acid metabolism and food intake, and it is an attractive target for drug discovery. It is an enzyme associated with Malonyl-CoA decarboxylase deficiency. In humans, it is encoded by the MLYCD gene.

Its main function is to catalyze the conversion of malonyl-CoA into acetyl-CoA and carbon dioxide. It is involved in fatty acid biosynthesis. To some degree, it reverses the action of Acetyl-CoA carboxylase.

malonyl-CoA decarboxylase
Human mitochondrial Malonyl-CoA decarboxylase. PDB 2ygw
Identifiers
EC no.4.1.1.9
CAS no.9024-99-1
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

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Structure

malonyl-CoA decarboxylase
Malonyl-CoA decarboxylase (mitochondrial, peroxisomal isoform) homotetramer, Human
Identifiers
SymbolMLYCD
NCBI gene23417
HGNC7150
OMIM606761
RefSeqNM_012213
UniProtO95822
Other data
EC number4.1.1.9
LocusChr. 16 q23-q24

MCD presents two isoforms which can be transcribed form one gene: a long isoform (54kDa), distributed in mitochondria, and a short isoform (49kDa) that can be found in peroxisomes and cytosol. The long isoform includes a sequence of signaling towards mitochondria in the N-terminus; whereas the short one only contains the typical sequence of peroxisomal signaling PTS1 in the C-terminus, also shared by the long isoform.

MCD is a protein tetramer, an oligomer formed by a dimer of heterodimers related by an axis of binary symmetry with a rotation angle of about 180 degrees. The strong structural asymmetry between the monomers of the heterodimer suggests a half of the sites reactivity, in which only half of the active sites are functional simultaneously. Each monomer contains basically two domains:

  • The N-terminus one, which is involved in oligomerization and has a helical structure of eight helixes organised as a bundle of four antiparallel helixes with two pairs of inserted helixes.
  • The C-terminus one is where malonyl-CoA catalysis takes place and which is present in GCN5- Histone acetyiltranferase family. It also includes a cluster of seven helixes.

However, the binding site for malonyl-CoA in MCD presents a variation with respect to their homologous: the center of the binding site has a glutamic residue instead of a glycine, acting as a molecular lever in the substrate releasing.

As said before, MCD presents a half of the sites reactivity, due to the fact that each heterodimer has two different structural conformations: B state (bound), in which the substrate is united; and U conformation (unbound), where the substrate union isn't allowed. According to this, the half of the sites mechanism might present a consumption of catalytic energy. Nevertheless, the conformational change produced in a subunit when changing from the B state to the U state (which produces the release of the product) coincides with the formation of a new union site in the active site of the neighbour subunit when changing from the U stat to B state. As a result, the conformational changes synchronised in the pair of subunits facilitates the catalysis despite the reduction of the number of available active sites.

Each monomer of that structure exhibits a large hydrophobic interface with the possibility to form an inter subunit disulfide bridge. Heterodimers are also interconnected by a small C-terminus domain interface, where a pair of cysteines is properly disposed. The disulfide bonds gives to MCD the capability to form a tetrameric enzyme linked by inter subunits covalent bonds in the presence of oxidants such as hydrogen peroxide.

Gene: MLYCD

The malonyl-CoA decarboxylase gene (MLYCD) is located in chromosome 16 (locus: 16q23.3). This gene has 2 transcripts or splice variants, one of which encodes MCD (the other doesn’t encode any protein). It has also 59 orthologues, 1 paralogue and it is associated with 5 phenotypes.

MLYCD is strongly expressed in heart, liver and some other tissues like kidney. This gene is also weakly expressed in many other tissues such as brain, placenta, testis, etc.

Processing and post-translational modifications

Malonyl-CoA decarboxylase is firstly processed as a pro-protein or proenzyme, in which the transit peptide, whose role is to transport the enzyme to a specific organelle (in this case the mitochondria), comprises the first 39 amino acids (beginning with a methionine and ending with an alanine). The polypeptide chain in the mature protein is comprised between amino acid 40 and 493.

In order to turn into an active enzyme, MCD undergoes 8 post-translational modifications (PTM) in different amino acids. The last one, which consists of an acetylation in the amino acid lysine in position 472, activates malonyl-CoA decarboxylase activity. Similarly, a deacetylation in this specific amino acid by SIRT4 (a mitochondrial protein) represses the enzyme activity, inhibiting fatty acid oxidation in muscle cells. Another important PTM is the formation of an interchain disulfide bond in the amino acid cysteine in position 206, which may take place in peroxisomes, as the cytosolic and mitochondrial environments are too reducing for this process.

Functions

The enzyme malonyl-CoA decarboxylase (MCD) functions as an indirect via of conversion from malonic semi aldehyde to acetyl-CoA in peroxisomes. This is due to the fact that the beta oxidation of long chain fatty acids with an odd number of carbons produces propionyl-CoA. Most part of this metabolite is transformed into succinyl-CoA, which is an intermediate of the tricarboxylic acid cycle. The major alternative route by which the propionyl-CoA is metabolized is based on its conversion to acrylyl-CoA. After that, it is converted to 3-hydroxy propionic acid and finally to malonic semi-aldehyde. As soon as malonic semi aldehyde is produced, it is indirectly transformed into acetyl-CoA. This conversion has been detected only in bacteria, in the other natural kingdoms there is no scientific evidence to prove it.

Malonyl-CoA is an important metabolite in some parts of the cell. In peroxisomes, the accumulation of this substance causes malonic aciduria, a highly pathogenic disease. To avoid it malonyl-CoA decarboxylase (MCD) converts malonyl-CoA into acetyl-CoA through the following reaction:

Reaction by which MDC transforms malonyl-CoA into acetyl-CoA

In the cytosol, malonyl-CoA can inhibit the entrance of fatty acids into the mitochondria and it can also act as a precursor for the fatty acids synthesis. Malonyl-CoA also plays an important role inside the mitochondria, where it is an intermediary between fatty acids and acetyl-CoA, which will be a reserve for the Krebs cycle.

Cytoplasmic MCD is thought to play a role in the regulation of cytoplasmic malonyl-CoA abundance and, therefore, of mitochondrial fatty acid uptake and oxidation.[9] It has been observed that MCD mRNA is most abundant in cardiac and skeletal muscles, tissues in which cytoplasmic malonyl-CoA is a strong inhibitor of mitochondrial fatty acid oxidation and which derive significant amounts of energy from fatty acid oxidation.

In peroxisomes, it is proposed that this enzyme could be involved in degrading intraperoxisomal malonyl-CoA, which is produced by the peroxisomal beta oxidation of odd chain length dicarboxylic fatty acids (odd chain length DFAs). While long and medium chain fatty acids are oxidized mainly in the mitochondria, DFAs are oxidized primarily in peroxisomes, which degrade DFAs completely to malonyl-CoA (in the case of odd chain length DFAs) and oxalyl-CoA (for even chain length DFAs). The peroxisomal form of MCD could function to eliminate this final malonyl-CoA.

Malonyl-CoA acts as an intermediary between fatty acids and acetyl-CoA in the mitochondria, where MCD is believed to participate in the elimination of the residual malonyl-CoA, so that acetyl-CoA can enter the Krebs cycle.

MCD also plays a role in the regulation of glucose and lipids as fuels in human tissues. Malonyl-CoA concentrations are crucial in the intracellular energetic regulation and the production or degradation of this metabolite delimits the use of glucose or lipids to produce ATP.

Pathology

The diseases related with MCD can be caused by its mislocalization, mutations affecting the gene MLYCD, its accumulation in peroxisomes and, mainly, its deficiency.

MCS deficiency is a rare autosomal disorder that is widely diagnosed by neonatal screening and it is caused by mutations in MLYCD. It causes many symptoms: brain abnormalities, mild mental retardation, seizures, hypotonia, metabolic acidosis, vomiting, excretion of malonic and methylmalonic acids in urine, cardiomyopathies, and hypoglycemia. More rarely, it can cause rheumatoid arthritis too.

In peroxisomes, the accumulation of MCD substance also causes pathological symptoms, which are similar to MCS deficiency: malonic aciduria, a lethal disease in which patients (normally children) have delayed development and can suffer from seizures, diarrhoea, hypoglycaemia and cardiomyopathy, as well.

Others symptoms caused by an altered action of MCD can be abdominal pain and chronic constipation.

Localization

Malonyl-CoA decarboxylase is present in the cytosolic, mitochondrial and peroxisomal compartments. MCD is found from bacteria to plants. In humans, MCD has been identified in heart, skeletal tissue, pancreas and kidneys. In rats, MCD has been detected in fat, heart and liver.

Enzyme regulation

Because the formation of interchain disulfide bonds leads to positive cooperativity between active sites and increases the affinity for malonyl-CoA and the catalytic efficiency (in vitro), MCD activity doesn't need the intervention of any cofactors or divalent metal ions.

Medical applications

MCD is involved in regulating cardiac malonyl-CoA levels, inhibition of MCD can limit rates of fatty acid oxidation, leading to a secondary increase in glucose oxidation associated with an improvement in the functional recovery of the heart during ischaemia/reperfusion injury. MCD is a potential novel target for cancer treatment.

Uranium in the environment

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Uranium_in_the_environment

Uranium in the environment is a global health concern, and comes from both natural and man-made sources. Mining, phosphates in agriculture, weapons manufacturing, and nuclear power are sources of uranium in the environment.

In the natural environment, radioactivity of uranium is generally low, but uranium is a toxic metal that can disrupt normal functioning of the kidney, brain, liver, heart, and numerous other systems. Chemical toxicity can cause public health issues when uranium is present in groundwater, especially if concentrations in food and water are increased by mining activity. The biological half-life (the average time it takes for the human body to eliminate half the amount in the body) for uranium is about 15 days.

Uranium's radioactivity can present health and environmental issues in the case of nuclear waste produced by nuclear power plants or weapons manufacturing.

Uranium is weakly radioactive and remains so because of its long physical half-life (4.468 billion years for uranium-238). The use of depleted uranium (DU) in munitions is controversial because of questions about potential long-term health effects.

Natural occurrence

Uranium ore

Uranium is a naturally occurring element found in low levels within all rock, soil, and water. This is the highest-numbered element to be found naturally in significant quantities on earth. According to the United Nations Scientific Committee on the Effects of Atomic Radiation the normal concentration of uranium in soil is 300 μg/kg to 11.7 mg/kg.

It is considered to be more plentiful than antimony, beryllium, cadmium, gold, mercury, silver, or tungsten and is about as abundant as tin, arsenic or molybdenum. It is found in many minerals including uraninite (most common uranium ore), autunite, uranophane, torbernite, and coffinite. Significant concentrations of uranium occur in some substances such as phosphate rock deposits, and minerals such as lignite, and monazite sands in uranium-rich ores (it is recovered commercially from these sources). Coal fly ash from uranium bearing coal is particularly rich in uranium and there have been several proposals to "mine" this waste product for its uranium content. Due to the fact that part of the ash of a coal power plant escapes through the smokestack, the radioactive contamination released by coal power plants in regular operation is actually higher than that of nuclear power plants.

Seawater contains about 3.3 parts per billion of uranium by weight, approximately (3.3 µg/kg) or, 3.3 micrograms per liter of seawater.

Sources of uranium

Mining and milling

Mining is the largest source of uranium contamination in the environment. Uranium milling creates radioactive waste in the form of tailings, which contain uranium, radium, and polonium. Consequently, uranium mining results in "the unavoidable radioactive contamination of the environment by solid, liquid and gaseous wastes".

Seventy percent of global uranium resources are on or adjacent to traditional lands belonging to Indigenous people, and perceived environmental risks associated with uranium mining have resulted in environmental conflicts involving multiple actors wherein local campaigns become national or international debates.

Some of these environmental conflicts have limited uranium exploration. Incidents at Ranger uranium mine in the Northern Territory of Australia and disputes over Indigenous land rights led to increased opposition to development of the nearby Jabiluka deposits and suspension of that project in the early 2000s. Similarly, environmental damage from Uranium mining on traditional Navajo lands in the southwestern United States resulted in restrictions on additional mining in Navajo lands in 2005.

Occupational hazards

The radiation hazards of uranium mining and milling were not appreciated in the early years, resulting in workers exposed to high levels of radiation. Inhalation of radon gas caused sharp increases in lung cancers among underground uranium miners employed in the 1940s and 1950s.

Military activity

DU penetrator from the PGU-14/B incendiary 30 mm round

Military activity is a source of uranium, especially at nuclear or munitions testing sites. Depleted uranium (DU) is a byproduct of uranium enrichment that is used for defensive armor plating and armor-piercing projectiles. Uranium contamination has been found at testing sites in the UK, in Kazakhstan, and in several countries as a result of DU munitions used in the Gulf War and the Yugoslav wars. During a three-week period of conflict in 2003 in Iraq, 1,000 to 2,000 tonnes of DU munitions were used.

Combustion and impact of DU munitions can produce aerosols that disperse uranium metal into the air and water where it can be inhaled or ingested by humans. A United Nations Environment Programme (UNEP) study has expressed concerns about groundwater contamination from these munitions. Studies of DU aerosol exposure suggest that uranium particles would quickly settle out of the air, and thus should not affect populations more than a few kilometres from target areas.

Sites in Kosovo and southern Central Serbia where NATO aviation used depleted uranium munitions during 1999 bombing

Nuclear energy and waste

The nuclear power industry is also a source of uranium in the environment in the form of radioactive waste or through nuclear accidents such as Three Mile Island or the Chernobyl disaster. Perceived risks of contamination associated with this industry contribute to the anti-nuclear movement.

In 2020, there were over 250,000 metric tons of high-level radioactive waste being stored globally in temporary containers. This waste is produced by nuclear power plants and weapons facilities, and is a serious human health and environmental issue. There are plans to permanently dispose of high-level waste in deep geological repositories, but none of these are operational. Corrosion of aging temporary containers has caused some waste to leak into the environment.

Spent uranium dioxide fuel is very insoluble in water, it is likely to release uranium (and fission products) even more slowly than borosilicate glass when in contact with water.

Health effects

Tiron

Soluble uranium salts are toxic, though less so than those of other heavy metals such as lead or mercury. The organ which is most affected is the kidney. Soluble uranium salts are readily excreted in the urine, although some accumulation in the kidneys does occur in the case of chronic exposure. The World Health Organization has established a daily "tolerated intake" of soluble uranium salts for the general public of 0.5 μg/kg body weight (or 35 μg for a 70 kg adult): exposure at this level is not thought to lead to any significant kidney damage.

Tiron may be used to remove uranium from the human body, in a form of chelation therapy. Bicarbonate may also be used as uranium (VI) forms complexes with the carbonate ion.

Public health

Uranium mining produces toxic tailings that are radioactive and may contain other toxic elements such as radon. Dust and water leaving tailing sites may carry long-lived radioactive elements that enter water sources and the soil, increase background radiation, and eventually be ingested by humans and animals. A 2013 analysis in a medical journal found that, "The effects of all these sources of contamination on human health will be subtle and widespread, and therefore difficult to detect both clinically and epidemiologically." A 2019 analysis of the global uranium industry said that the industry was shifting mining activities toward the Global South where environmental regulations are typically less stringent; and that people in impacted communities would "surely experience adverse environmental consequences" and public health issues arising from mining activities carried out by powerful multi-national corporations or mining companies based in foreign countries.

Cancer

In 1950, the US Public Health service began a comprehensive study of uranium miners, leading to the first publication of a statistical correlation between cancer and uranium mining, released in 1962. The federal government eventually regulated the standard amount of radon in mines, setting the level at 0.3 WL on January 1, 1969.

Out of 69 present and former uranium milling sites in 12 states, 24 have been abandoned, and are the responsibility of the US Department of Energy. Accidental releases from uranium mills include the 1979 Church Rock uranium mill spill in New Mexico, called the largest accident of nuclear-related waste in US history, and the 1986 Sequoyah Corporation Fuels Release in Oklahoma.

In 1990, Congress passed the Radiation Exposure Compensation Act (RECA), granting reparations for those affected by mining, with amendments passed in 2000 to address criticisms with the original act.

Depleted uranium exposure studies

The use of depleted uranium (DU) in munitions is controversial because of questions about potential long-term health effects. Normal functioning of the kidney, brain, liver, heart, and numerous other systems can be affected by uranium exposure, because uranium is a toxic metal. Some people have raised concerns about the use of DU munitions because of its mutagenicity, teratogenicity in mice, neurotoxicity, and its suspected carcinogenic potential. Additional concerns address unexploded DU munitions leeching into groundwater over time.

The toxicity of DU is a point of medical controversy. Multiple studies using cultured cells and laboratory rodents suggest the possibility of leukemogenic, genetic, reproductive, and neurological effects from chronic exposure. A 2005 epidemiology review concluded: "In aggregate the human epidemiological evidence is consistent with increased risk of birth defects in offspring of persons exposed to DU." The World Health Organization states that no risk of reproductive, developmental, or carcinogenic effects have been reported in humans due to DU exposure. This report has been criticized by Dr. Keith Baverstock for not including possible long-term effects.

Birth defects

Most scientific studies have found no link between uranium and birth defects, but some claim statistical correlations between soldiers exposed to DU, and those who were not, concerning reproductive abnormalities.

One study found epidemiological evidence for increased risk of birth defects in the offspring of persons exposed to DU. Several sources have attributed an increased rate of birth defects in the children of Gulf War veterans and in Iraqis to inhalation of depleted uranium. A 2001 study of 15,000 Gulf War combat veterans and 15,000 control veterans found that the Gulf War veterans were 1.8 (fathers) to 2.8 (mothers) times more likely to have children with birth defects. A study of Gulf War Veterans from the UK found a 50% increased risk of malformed pregnancies reported by men over non-Gulf War veterans. The study did not find correlations between Gulf war deployment and other birth defects such as stillbirth, chromosomal malformations, or congenital syndromes. The father's service in the Gulf War was associated with increased rate of miscarriage, but the mother's service was not.

In animals

Uranium causes reproductive defects and other health problems in rodents, frogs and other animals. Uranium was also shown to have cytotoxic, genotoxic and carcinogenic effects in animals. It has been shown in rodents and frogs that water-soluble forms of uranium are teratogenic.

In soil and microbiology

Bacteria and Pseudomonadota, such as Geobacter and Burkholderia fungorum (strain Rifle), can reduce and fix uranium in soil and groundwater.These bacteria change soluble U(VI) into the highly insoluble complex-forming U(IV) ion, hence stopping chemical leaching.

It has been suggested that it is possible to form a reactive barrier by adding something to the soil which will cause the uranium to become fixed. One method of doing this is to use a mineral (apatite) while a second method is to add a food substance such as acetate to the soil. This will enable bacteria to reduce the uranium(VI) to uranium(IV), which is much less soluble. In peat-like soils, the uranium will tend to bind to the humic acids; this tends to fix the uranium in the soil.

Steroid hormone

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Steroid_hormone
 
Steroid hormone

Estradiol, an important estrogen steroid hormone in both women and men.
Class identifiers
SynonymsAdrenal steroid; Gonadal steroid
UseVarious
Biological targetSteroid hormone receptors
Chemical classSteroidal; Nonsteroidal

A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence cortico-) and sex steroids (typically made in the gonads or placenta). Within those two classes are five types according to the receptors to which they bind: glucocorticoids and mineralocorticoids (both corticosteroids) and androgens, estrogens, and progestogens (sex steroids). Vitamin D derivatives are a sixth closely related hormone system with homologous receptors. They have some of the characteristics of true steroids as receptor ligands.

Steroid hormones help control metabolism, inflammation, immune functions, salt and water balance, development of sexual characteristics, and the ability to withstand injury and illness. The term steroid describes both hormones produced by the body and artificially produced medications that duplicate the action for the naturally occurring steroids.

Synthesis

Steroidogenesis with enzymes and intermediates.

The natural steroid hormones are generally synthesized from cholesterol in the gonads and adrenal glands. These forms of hormones are lipids. They can pass through the cell membrane as they are fat-soluble, and then bind to steroid hormone receptors (which may be nuclear or cytosolic depending on the steroid hormone) to bring about changes within the cell. Steroid hormones are generally carried in the blood, bound to specific carrier proteins such as sex hormone-binding globulin or corticosteroid-binding globulin. Further conversions and catabolism occurs in the liver, in other "peripheral" tissues, and in the target tissues.

Synthetic steroids and sterols

A variety of synthetic steroids and sterols have also been contrived. Most are steroids, but some nonsteroidal molecules can interact with the steroid receptors because of a similarity of shape. Some synthetic steroids are weaker or stronger than the natural steroids whose receptors they activate.

Some examples of synthetic steroid hormones:

Some steroid antagonists:

Transport

Free hormone hypothesis 2

Steroid hormones are transported through the blood by being bound to carrier proteins—serum proteins that bind them and increase the hormones' solubility in water. Some examples are sex hormone-binding globulin (SHBG), corticosteroid-binding globulin, and albumin. Most studies say that hormones can only affect cells when they are not bound by serum proteins. In order to be active, steroid hormones must free themselves from their blood-solubilizing proteins and either bind to extracellular receptors, or passively cross the cell membrane and bind to nuclear receptors. This idea is known as the free hormone hypothesis. This idea is shown in Figure 1 to the right.

This shows a possible pathway through which steroid hormones are endocytosed and proceed to affect cells via a genomic pathway.

One study has found that these steroid-carrier complexes are bound by megalin, a membrane receptor, and are then taken into cells via endocytosis. One possible pathway is that once inside the cell these complexes are taken to the lysosome, where the carrier protein is degraded and the steroid hormone is released into the cytoplasm of the target cell. The hormone then follows a genomic pathway of action. This process is shown in Figure 2 to the right. The role of endocytosis in steroid hormone transport is not well understood and is under further investigation.

In order for steroid hormones to cross the lipid bilayer of cells, they must overcome energetic barriers that would prevent their entering or exiting the membrane. Gibbs free energy is an important concept here. These hormones, which are all derived from cholesterol, have hydrophilic functional groups at either end and hydrophobic carbon backbones. When steroid hormones are entering membranes free energy barriers exist when the functional groups are entering the hydrophobic interior of membrane, but it is energetically favorable for the hydrophobic core of these hormones to enter lipid bilayers. These energy barriers and wells are reversed for hormones exiting membranes. Steroid hormones easily enter and exit the membrane at physiologic conditions. They have been shown experimentally to cross membranes near a rate of 20 μm/s, depending on the hormone.

Though it is energetically more favorable for hormones to be in the membrane than in the ECF or ICF, they do in fact leave the membrane once they have entered it. This is an important consideration because cholesterol—the precursor to all steroid hormones—does not leave the membrane once it has embedded itself inside. The difference between cholesterol and these hormones is that cholesterol is in a much larger negative Gibb's free energy well once inside the membrane, as compared to these hormones. This is because the aliphatic tail on cholesterol has a very favorable interaction with the interior of lipid bilayers.

Mechanisms of action and effects

There are many different mechanisms through which steroid hormones affect their target cells. All of these different pathways can be classified as having either a genomic effect or a non-genomic effect. Genomic pathways are slow and result in altering transcription levels of certain proteins in the cell; non-genomic pathways are much faster.

Flowchart showing the binding of a steroid hormone to a target cell

Genomic pathways

The first identified mechanisms of steroid hormone action were the genomic effects. In this pathway, the free hormones first pass through the cell membrane because they are fat soluble. In the cytoplasm, the steroid may or may not undergo an enzyme-mediated alteration such as reduction, hydroxylation, or aromatization. Then the steroid binds to a specific steroid hormone receptor, also known as a nuclear receptor, which is a large metalloprotein. Upon steroid binding, many kinds of steroid receptors dimerize: two receptor subunits join together to form one functional DNA-binding unit that can enter the cell nucleus. Once in the nucleus, the steroid-receptor ligand complex binds to specific DNA sequences and induces transcription of its target genes.

Non-genomic pathways

Because non-genomic pathways include any mechanism that is not a genomic effect, there are various non-genomic pathways. However, all of these pathways are mediated by some type of steroid hormone receptor found at the plasma membrane. Ion channels, transporters, G-protein coupled receptors (GPCR), and membrane fluidity have all been shown to be affected by steroid hormones. Of these, GPCR linked proteins are the most common. For more information on these proteins and pathways, visit the steroid hormone receptor page.

Introduction to entropy

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