2FY2 , 2FY3 , 2FY4 , 2FY5
71-411: 1103 12647 ENSG00000070748 ENSMUSG00000021919 P28329 Q8BQV2 NM_020984 NM_020985 NM_009891 NP_066265 NP_066266 NP_034021 Choline acetyltransferase (commonly abbreviated as ChAT , but sometimes CAT ) is a transferase enzyme responsible for the synthesis of the neurotransmitter acetylcholine . ChAT catalyzes the transfer of an acetyl group from
142-404: A DNA methyltransferase is a transferase that catalyzes the transfer of a methyl group to a DNA acceptor. In practice, many molecules are not referred to using this terminology due to more prevalent common names. For example, RNA polymerase is the modern common name for what was formerly known as RNA nucleotidyltransferase, a kind of nucleotidyl transferase that transfers nucleotides to
213-423: A hydrogen bond between choline's hydroxyl group and a histidine residue, His324. The choline substrate fits into a pocket in the interior of ChAT, while acetyl-CoA fits into a pocket on the surface of the protein. The 3D crystal structure shows the acetyl group of acetyl-CoA abuts the choline binding pocket – minimizing the distance between acetyl-group donor and receiver. ChAT is very conserved across
284-428: A simple sugar . This deficiency occurs when the gene for galactose-1-phosphate uridylyltransferase (GALT) has any number of mutations, leading to a deficiency in the amount of GALT produced. There are two forms of Galactosemia: classic and Duarte. Duarte galactosemia is generally less severe than classic galactosemia and is caused by a deficiency of galactokinase . Galactosemia renders infants unable to process
355-420: A transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups (e.g. a methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor). They are involved in hundreds of different biochemical pathways throughout biology, and are integral to some of life's most important processes. Transferases are involved in myriad reactions in
426-542: A 30 to 90% reduction in activity in several regions of the brain, including the temporal lobe , the parietal lobe and the frontal lobe . However, ChAT deficiency is not believed to be the main cause of this disease. Patients with ALS show a marked decrease in ChAT activity in motor neurons in the spinal cord and brain . Low levels of ChAT activity are an early indication of the disease and are detectable long before motor neurons begin to die. This can even be detected before
497-400: A BMD phenotype. The genetic mutation that leads to Becker muscular dystrophy is an in-frame deletion . This means that, out of the 79 exons that code for dystrophin, one or several in the middle may be removed, without affecting the exons that follow the deletion. This allows for a shorter-than-normal dystrophin protein that maintains a degree of functionality. In Duchenne muscular dystrophy,
568-466: A bond, not a minus sign), X would be the donor, and Y would be the acceptor. R denotes the functional group transferred as a result of transferase activity. The donor is often a coenzyme . Some of the most important discoveries relating to transferases occurred as early as the 1930s. Earliest discoveries of transferase activity occurred in other classifications of enzymes , including beta-galactosidase , protease , and acid/base phosphatase . Prior to
639-484: A carbamoyl group from one molecule to another. Carbamoyl groups follow the formula NH 2 CO. In ATCase such a transfer is written as carbamoyl phosphate + L- aspartate → {\displaystyle \rightarrow } L-carbamoyl aspartate + phosphate . Enzymes that transfer aldehyde or ketone groups and included in EC 2.2. This category consists of various transketolases and transaldolases. Transaldolase,
710-505: A central rod domain consisting of repetitive and partially dispensable segments. Dystrophin’s function is to maintain muscle fiber stability during contraction by linking the extra cellular matrix to the cytoskeleton. Mutations that disrupt the open reading frame within dystrophin create prematurely truncated proteins that are unable to perform their job. Such mutations lead to muscle fiber damage, replacement of muscle tissue by fat and fibrotic tissue, and premature death typically occurring in
781-644: A change in electroretinogram activity. The human gene responsible for encoding ChAT is CHAT. Mutations in CHAT have been linked to congenital myasthenic syndrome , a disease which leads to general motor function deficiency and weakness. Further symptoms include fatal apnea . Out of ten isolated mutants, 1 has been shown to lack activity completely, 8 have been shown to have significantly decreased activity, and 1 has an unknown function. The Alzheimer's disease (AD) involves difficulty in memory and cognition. The concentrations of acetylcholine and ChAT are remarkably reduced in
SECTION 10
#1733085940260852-442: A classification of EC2 . Hydrogen is not considered a functional group when it comes to transferase targets; instead, hydrogen transfer is included under oxidoreductases , due to electron transfer considerations. EC 2.1 includes enzymes that transfer single-carbon groups. This category consists of transfers of methyl , hydroxymethyl , formyl, carboxy, carbamoyl , and amido groups. Carbamoyltransferases, as an example, transfer
923-443: A mutation specific antisense oligonucleotide (AON). An antisense oligonucleotide is a synthesized short nucleic acid polymer, typically fifty or fewer base pairs in length that will bind to the mutation site in the pre-messenger RNA, to induce exon skipping. The AON binds to the mutated exon, so that when the gene is then translated from the mature mRNA, it is “skipped” over, thus restoring the disrupted reading frame. This allows for
994-456: A nerve cell classifies this cell as a "cholinergic" neuron. In humans, the choline acetyltransferase enzyme is encoded by the CHAT gene . Choline acetyltransferase was first described by David Nachmansohn and A. L. Machado in 1943. A German biochemist, Nachmansohn had been studying the process of nerve impulse conduction and utilization of energy-yielding chemical reactions in cells, expanding upon
1065-633: A severe DMD mutation into a less harmful in-frame BMD mutation. One exon-skipping drug was approved in 2016, by the US FDA: eteplirsen (ExonDys51), a Morpholino oligo from Sarepta Therapeutics targeting exon 51 of human dystrophin. Another exon-skipping Morpholino, golodirsen (Vyondys 53) (targeting dystrophin exon 53), was approved in the United States in December 2019. A third antisense oligonucleotide , viltolarsen (Viltepso), targeting dystrophin exon 53
1136-506: A single transmembrane helix , for example numerous glycosyltransferases in Golgi apparatus . Some others are multi-span transmembrane proteins , for example certain oligosaccharyltransferases or microsomal glutathione S-transferase from MAPEG family . Exon skipping In molecular biology , exon skipping is a form of RNA splicing used to cause cells to “skip” over faulty or misaligned sections ( exons ) of genetic code, leading to
1207-691: A sulfate group donor. Within this group is alcohol sulfotransferase which has a broad targeting capacity. Due to this, alcohol sulfotransferase is also known by several other names including "hydroxysteroid sulfotransferase," "steroid sulfokinase," and "estrogen sulfotransferase." Decreases in its activity has been linked to human liver disease. This transferase acts via the following reaction: 3'-phosphoadenylyl sulfate + an alcohol ⇌ {\displaystyle \rightleftharpoons } adenosine 3',5'bisphosphate + an alkyl sulfate. EC 2.9 includes enzymes that transfer selenium -containing groups. This category only contains two transferases, and thus
1278-432: A truncated but still functional protein despite the genetic mutation. Exon skipping is used to restore the reading frame within a gene. Genes are the genetic instructions for creating a protein, and are composed of introns and exons . Exons are the sections of DNA that contain the instruction set for generating a protein; they are interspersed with non-coding regions called introns. The introns are later removed before
1349-501: Is EC 2.6. This includes enzymes like transaminase (also known as "aminotransferase"), and a very small number of oximinotransferases and other nitrogen group transferring enzymes. EC 2.6 previously included amidinotransferase but it has since been reclassified as a subcategory of EC 2.1 (single-carbon transferring enzymes). In the case of aspartate transaminase , which can act on tyrosine , phenylalanine , and tryptophan , it reversibly transfers an amino group from one molecule to
1420-518: Is a component of MoCo biosynthesis in Escherichia coli . The reaction it catalyzes is as follows: adenylyl- molybdopterin + molybdate → {\displaystyle \rightarrow } molybdenum cofactor + AMP. The A and B transferases are the foundation of the human ABO blood group system. Both A and B transferases are glycosyltransferases, meaning they transfer a sugar molecule onto an H-antigen. This allows H-antigen to synthesize
1491-639: Is a subcategory of EC 2.4 transferases that is involved in biosynthesis of disaccharides and polysaccharides through transfer of monosaccharides to other molecules. An example of a prominent glycosyltransferase is lactose synthase which is a dimer possessing two protein subunits . Its primary action is to produce lactose from glucose and UDP-galactose. This occurs via the following pathway: UDP-β-D-galactose + D-glucose ⇌ {\displaystyle \rightleftharpoons } UDP + lactose. EC 2.5 relates to enzymes that transfer alkyl or aryl groups, but does not include methyl groups. This
SECTION 20
#17330859402601562-451: Is called choline acetylase. The acetyl transferase mode of action was unknown at the time of this discovery, however Nachmansohn hypothesized the possibility of acetylphosphate or phosphorylcholine exchanging the phosphate (from ATP ) for choline or acetate ion. It was not until 1945 that Coenzyme A (CoA) was discovered simultaneously and independently by three laboratories, Nachmansohn's being one of these. Subsequently, acetyl-CoA, at
1633-560: Is caused by mutation in the gene OXCT1. Treatments mostly rely on controlling the diet of the patient. Carnitine palmitoyltransferase II deficiency (also known as CPT-II deficiency ) leads to an excess long chain fatty acids , as the body lacks the ability to transport fatty acids into the mitochondria to be processed as a fuel source. The disease is caused by a defect in the gene CPT2. This deficiency will present in patients in one of three ways: lethal neonatal, severe infantile hepatocardiomuscular, and myopathic form. The myopathic
1704-403: Is globular in shape and consists of a single amino acid chain. ChAT functions to transfer an acetyl group from acetyl co-enzyme A to choline in the synapses of nerve cells and exists in two forms: soluble and membrane bound. The ChAT gene is located on chromosome 10 . Decreased expression of ChAT is one of the hallmarks of Alzheimer's disease . Patients with Alzheimer's disease show
1775-521: Is in contrast to functional groups that become alkyl groups when transferred, as those are included in EC 2.3. EC 2.5 currently only possesses one sub-class: Alkyl and aryl transferases. Cysteine synthase , for example, catalyzes the formation of acetic acids and cysteine from O 3 -acetyl-L-serine and hydrogen sulfide : O 3 -acetyl-L-serine + H 2 S ⇌ {\displaystyle \rightleftharpoons } L-cysteine + acetate. The grouping consistent with transfer of nitrogenous groups
1846-402: Is largely dispensable. Dystrophin can maintain a large degree of functionality so long as the essential terminal domains are unaffected, and exon skipping only occurs within the central rod domain. Given these parameters, exon skipping can be used to restore an open reading frame by inducing a deletion of one or several exons within the central rod domain, and thus converting a DMD phenotype into
1917-403: Is one of the smallest categories of transferase. Selenocysteine synthase, which was first added to the classification system in 1999, converts seryl-tRNA(Sec UCA) into selenocysteyl-tRNA(Sec UCA). The category of EC 2.10 includes enzymes that transfer molybdenum or tungsten -containing groups. However, as of 2011, only one enzyme has been added: molybdopterin molybdotransferase . This enzyme
1988-574: Is possible for Homo sapiens to have any of four different blood types : Type A (express A antigens), Type B (express B antigens), Type AB (express both A and B antigens) and Type O (express neither A nor B antigens). The gene for A and B transferases is located on chromosome 9 . The gene contains seven exons and six introns and the gene itself is over 18kb long. The alleles for A and B transferases are extremely similar. The resulting enzymes only differ in 4 amino acid residues. The differing residues are located at positions 176, 235, 266, and 268 in
2059-514: Is the functional group transferred by a peptidyl transferase . The transfer involves the removal of the growing amino acid chain from the tRNA molecule in the A-site of the ribosome and its subsequent addition to the amino acid attached to the tRNA in the P-site . Mechanistically, an enzyme that catalyzed the following reaction would be a transferase: In the above reaction (where the dash represents
2130-516: Is the least severe form of the deficiency and can manifest at any point in the lifespan of the patient. The other two forms appear in infancy. Common symptoms of the lethal neonatal form and the severe infantile forms are liver failure, heart problems, seizures and death. The myopathic form is characterized by muscle pain and weakness following vigorous exercise. Treatment generally includes dietary modifications and carnitine supplements. Galactosemia results from an inability to process galactose,
2201-676: The amino acid sequence is very similar; however, pChAT is missing parts of the sequence present in cChAT. The pChAT isoform was discovered in 2000 based on observations that brain-derived ChAT antibodies failed to stain peripheral cholinergic neurons as they do for those found in the brain. This gene splicing mechanism which leads to cChAT and pChAT differences has been observed in various species, including both vertebrate mammals and invertebrate mollusks, suggesting this mechanism leads to some yet-unidentified evolutionary advantage. Cholinergic systems are implicated in numerous neurologic functions. Alteration in some cholinergic neurons may account for
Choline acetyltransferase - Misplaced Pages Continue
2272-611: The cardiovascular and respiratory systems. CMS is a family of diseases that are characterized by defects in neuromuscular transmission which leads to recurrent bouts of apnea (inability to breathe) that can be fatal. ChAT deficiency is implicated in myasthenia syndromes where the transition problem occurs presynaptically . These syndromes are characterized by the patients’ inability to resynthesize acetylcholine . Terminal transferases are transferases that can be used to label DNA or to produce plasmid vectors . It accomplishes both of these tasks by adding deoxynucleotides in
2343-400: The coenzyme acetyl-CoA to choline , yielding acetylcholine (ACh). ChAT is found in high concentration in cholinergic neurons , both in the central nervous system (CNS) and peripheral nervous system (PNS). As with most nerve terminal proteins, ChAT is produced in the body of the neuron and is transported to the nerve terminal , where its concentration is highest. Presence of ChAT in
2414-477: The glycoprotein and glycolipid conjugates that are known as the A/B antigens . The full name of A transferase is alpha 1-3-N-acetylgalactosaminyltransferase and its function in the cell is to add N-acetylgalactosamine to H-antigen, creating A-antigen. The full name of B transferase is alpha 1-3-galactosyltransferase, and its function in the cell is to add a galactose molecule to H-antigen, creating B-antigen. It
2485-482: The 3’ end of a growing RNA strand. In the EC system of classification, the accepted name for RNA polymerase is DNA-directed RNA polymerase. Described primarily based on the type of biochemical group transferred, transferases can be divided into ten categories (based on the EC Number classification). These categories comprise over 450 different unique enzymes. In the EC numbering system, transferases have been given
2556-579: The CDK-cyclin complex is capable of enacting its function within the cell cycle. The reaction catalyzed by CDK is as follows: ATP + a target protein → {\displaystyle \rightarrow } ADP + a phosphoprotein. Transfer of sulfur-containing groups is covered by EC 2.8 and is subdivided into the subcategories of sulfurtransferases, sulfotransferases, and CoA-transferases, as well as enzymes that transfer alkylthio groups. A specific group of sulfotransferases are those that use PAPS as
2627-399: The animal genome. Among mammals, in particular, there is very high sequence similarity. Human and cat ( Felis catus ) ChAT, for example, have 89% sequence identity. Sequence identity with Drosophila is about 30%. There are two forms of ChAT: Soluble form and membrane-bound form. The soluble form accounts for 80-90% of the total enzyme activity while the membrane-bound form is responsible for
2698-466: The brain and the nucleus accumbens , which is believed to correlate with the decreased cognitive functioning experienced by these patients. Recent studies have shown that SIDS infants show decreased levels of ChAT in both the hypothalamus and the striatum . SIDS infants also display fewer neurons capable of producing ChAT in the vagus system. These defects in the medulla could lead to an inability to control essential autonomic functions such as
2769-411: The cell. Three examples of these reactions are the activity of coenzyme A (CoA) transferase , which transfers thiol esters , the action of N-acetyltransferase , which is part of the pathway that metabolizes tryptophan , and the regulation of pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl CoA . Transferases are also utilized during translation. In this case, an amino acid chain
2840-463: The cerebral neocortex and hippocampus. Although the cellular loss and dysfunction of the cholinergic neurones is considered a contributor to Alzheimer disease, it is generally not considered as a primary factor in the development of this disease. It is proposed that the aggregation and deposition of the Beta amyloid protein, interferes with the metabolism of neurones and further damages the cholinergic axons in
2911-505: The cha-1 gene. All mutations result in a significant drop in ChAT activity. Percent activity loss can be greater than 98% in some cases. Phenotypic effects include slowed growth, decreased size, uncoordinated behavior, and lack of sensitivity toward cholinesterase inhibitors . Isolated temperature-sensitive mutants in Drosophila have all been lethal. Prior to death, affected flies show a change in behavior, including uncontrolled movements and
Choline acetyltransferase - Misplaced Pages Continue
2982-507: The control of visceral functions such as, but not limited to, cardiac muscle contraction and gastrointestinal tract function. It is often used as an immunohistochemical marker for motor neurons (motoneurons). Mutants of ChAT have been isolated in several species, including C. elegans , Drosophila , and humans. Most non-lethal mutants that have a non-wild type phenotype exhibit some activity, but significantly less than wild type. In C. elegans , several mutations in ChAT have been traced to
3053-760: The cortex and cholinergic neurones in the basal forebrain. The amyotrophic lateral sclerosis (ALS) is one of the most common motor neuron diseases. A significant loss of ChAT immunoreactivity is found in ALS. It is hypothesized that the cholinergic function is involved in an uncontrolled increase of intracellular calcium concentration whose reason still remains unclear. Neostigmine methylsulfate, an anticholinesterase agent, has been used to target ChAT. In particular, use of neostigmine methylsulfate has been shown to have positive effects against congenital myasthenic syndrome. Exposure to estradiol has been shown to increase ChAT in female rats. Transferase In biochemistry ,
3124-422: The discovery of uridyl transferase. In 1953, the enzyme UDP-glucose pyrophosphorylase was shown to be a transferase, when it was found that it could reversibly produce UTP and G1P from UDP-glucose and an organic pyrophosphate . Another example of historical significance relating to transferase is the discovery of the mechanism of catecholamine breakdown by catechol-O-methyltransferase . This discovery
3195-418: The disturbances of Alzheimer disease . The protein encoded by this gene synthesizes the neurotransmitter acetylcholine . Acetylcholine acts at two classes of receptors in the central nervous system – muscarinic and nicotinic – which are each implicated in different physiological responses. The role of acetylcholine at the nicotinic receptor is still under investigation. It is likely implicated in
3266-446: The early twenties of DMD patients. Comparatively, mutations that do not upset the open reading frame, lead to a dystrophin protein that is internally deleted and shorter than normal, but still partially functional. Such mutations are associated with the much milder Becker muscular dystrophy. Mildly affected BMD patients carrying deletions that involve over two thirds of the central rod domain have been described, suggesting that this domain
3337-676: The enzymes. . Transferase deficiencies are at the root of many common illnesses . The most common result of a transferase deficiency is a buildup of a cellular product . Succinyl-CoA:3-ketoacid CoA transferase deficiency (or SCOT deficiency ) leads to a buildup of ketones . Ketones are created upon the breakdown of fats in the body and are an important energy source. Inability to utilize ketones leads to intermittent ketoacidosis , which usually first manifests during infancy. Disease sufferers experience nausea, vomiting, inability to feed, and breathing difficulties. In extreme cases, ketoacidosis can lead to coma and death. The deficiency
3408-564: The form of "donor:acceptor grouptransferase." For example, methylamine:L-glutamate N-methyltransferase would be the standard naming convention for the transferase methylamine-glutamate N-methyltransferase , where methylamine is the donor, L-glutamate is the acceptor, and methyltransferase is the EC category grouping. This same action by the transferase can be illustrated as follows: However, other accepted names are more frequently used for transferases, and are often formed as "acceptor grouptransferase" or "donor grouptransferase." For example,
3479-401: The form of a template to the downstream end or 3' end of an existing DNA molecule. Terminal transferase is one of the few DNA polymerases that can function without an RNA primer. The family of glutathione transferases (GST) is extremely diverse, and therefore can be used for a number of biotechnological purposes. Plants use glutathione transferases as a means to segregate toxic metals from
3550-426: The generation of an internally deleted, but largely functional protein. Some mutations require exon skipping at multiple sites, sometimes adjacent to one another, in order to restore the reading frame. Multiple exon skipping has successfully been carried out using a combination of AONs that target multiple exons. Exon skipping is being heavily researched for the treatment of Duchenne muscular dystrophy (DMD), where
3621-454: The genetic mutation is out-of-frame. Out-of-frame mutations cause a premature stop in protein generation - the ribosome is unable to “read” the RNA past the point of initial error - leading to a severely shortened and completely non-functional dystrophin protein. The goal of exon skipping is to manipulate the splicing pattern so that an out-of-frame mutation becomes an in-frame mutation, thus changing
SECTION 50
#17330859402603692-457: The muscular protein dystrophin is prematurely truncated, which leads to a non-functioning protein. Successful treatment by way of exon skipping could lead to a mostly functional dystrophin protein, and create a phenotype similar to the less severe Becker muscular dystrophy (BMD). In the case of Duchenne muscular dystrophy, the protein that becomes compromised is dystrophin. The dystrophin protein has two essential functional domains that flank
3763-519: The namesake of aldehyde transferases, is an important part of the pentose phosphate pathway. The reaction it catalyzes consists of a transfer of a dihydroxyacetone functional group to glyceraldehyde 3-phosphate (also known as G3P). The reaction is as follows: sedoheptulose 7-phosphate + glyceraldehyde 3-phosphate ⇌ {\displaystyle \rightleftharpoons } erythrose 4-phosphate + fructose 6-phosphate . Transfer of acyl groups or acyl groups that become alkyl groups during
3834-635: The only available commercial source of natural rubber is the Hevea plant ( Hevea brasiliensis ). Natural rubber is superior to synthetic rubber in a number of commercial uses. Efforts are being made to produce transgenic plants capable of synthesizing natural rubber, including tobacco and sunflower . These efforts are focused on sequencing the subunits of the rubber transferase enzyme complex in order to transfect these genes into other plants. Many transferases associate with biological membranes as peripheral membrane proteins or anchored to membranes through
3905-420: The only available treatment is early diagnosis followed by adherence to a diet devoid of lactose, and prescription of antibiotics for infections that may develop. Choline acetyltransferase (also known as ChAT or CAT) is an important enzyme which produces the neurotransmitter acetylcholine . Acetylcholine is involved in many neuropsychic functions such as memory, attention, sleep and arousal. The enzyme
3976-429: The other. The reaction, for example, follows the following order: L-aspartate +2-oxoglutarate ⇌ {\displaystyle \rightleftharpoons } oxaloacetate + L-glutamate. While EC 2.7 includes enzymes that transfer phosphorus -containing groups, it also includes nuclotidyl transferases as well. Sub-category phosphotransferase is divided up in categories based on the type of group that accepts
4047-418: The patient is symptomatic . Patients with Huntington's also show a marked decrease in ChAT production. Though the specific cause of the reduced production is not clear, it is believed that the death of medium-sized motor neurons with spiny dendrites leads to the lower levels of ChAT production. Patients with Schizophrenia also exhibit decreased levels of ChAT, localized to the mesopontine tegment of
4118-660: The process of being transferred are key aspects of EC 2.3. Further, this category also differentiates between amino-acyl and non-amino-acyl groups. Peptidyl transferase is a ribozyme that facilitates formation of peptide bonds during translation . As an aminoacyltransferase, it catalyzes the transfer of a peptide to an aminoacyl-tRNA , following this reaction: peptidyl-tRNA A + aminoacyl-tRNA B ⇌ {\displaystyle \rightleftharpoons } tRNA A + peptidyl aminoacyl-tRNA B . EC 2.4 includes enzymes that transfer glycosyl groups, as well as those that transfer hexose and pentose. Glycosyltransferase
4189-400: The protein is made, leaving only the coding exon regions. Splicing naturally occurs in pre-mRNA when introns are being removed to form mature-mRNA that consists solely of exons. Starting in the late 1990s, scientists realized they could take advantage of this naturally occurring cellular splicing to downplay genetic mutations into less harmful ones. The mechanism behind exon skipping is
4260-460: The realization that individual enzymes were capable of such a task, it was believed that two or more enzymes enacted functional group transfers. Transamination , or the transfer of an amine (or NH 2 ) group from an amino acid to a keto acid by an aminotransferase (also known as a "transaminase"), was first noted in 1930 by Dorothy M. Needham , after observing the disappearance of glutamic acid added to pigeon breast muscle. This observance
4331-599: The rest of 10-20% activity. However, there has long been a debate on how the latter form of ChAT is bound to the membrane. The membrane-bound form of ChAT is associated with synaptic vesicles. There exist two isoforms of ChAT, both encoded by the same sequence. The common type ChAT (cChAT) is present in both the CNS and PNS. Peripheral type ChAT (pChAT) is preferentially expressed in the PNS in humans, and arises from exon skipping (exons 6–9) during post-transcriptional modification . Therefore,
SECTION 60
#17330859402604402-600: The rest of the cell. These glutathione transferases can be used to create biosensors to detect contaminants such as herbicides and insecticides. Glutathione transferases are also used in transgenic plants to increase resistance to both biotic and abiotic stress. Glutathione transferases are currently being explored as targets for anti-cancer medications due to their role in drug resistance . Further, glutathione transferase genes have been investigated due to their ability to prevent oxidative damage and have shown improved resistance in transgenic cultigens . Currently
4473-443: The reward/reinforcement pathways, as indicated by the addictive nature of nicotine , which also binds to the nicotinic receptor. The muscarinic action of acetylcholine in the CNS is implicated in learning and memory. The loss of cholinergic innervation in the neocortex has been associated with memory loss, as is evidenced in advanced cases of Alzheimer's disease. In the peripheral nervous system , cholinergic neurons are implicated in
4544-409: The sugars in breast milk, which leads to vomiting and anorexia within days of birth. Most symptoms of the disease are caused by a buildup of galactose-1-phosphate in the body. Common symptoms include liver failure, sepsis , failure to grow, and mental impairment, among others. Buildup of a second toxic substance, galactitol , occurs in the lenses of the eyes, causing cataracts . Currently,
4615-410: The time called “active acetate,” was discovered in 1951. The 3D structure of rat-derived ChAT was not solved until nearly 60 years later, in 2004. The 3D structure of ChAT has been solved by X-ray crystallography PDB : 2FY2 . Choline is bound in the active site of ChAT by non-covalent interactions between the positively charged amine of choline and the hydroxyl group of Tyr552, in addition to
4686-442: The transfer. Groups that are classified as phosphate acceptors include: alcohols, carboxy groups, nitrogenous groups, and phosphate groups. Further constituents of this subclass of transferases are various kinases. A prominent kinase is cyclin-dependent kinase (or CDK), which comprises a sub-family of protein kinases . As their name implies, CDKs are heavily dependent on specific cyclin molecules for activation . Once combined,
4757-482: The works of Nobel laureates Otto Warburg and Otto Meyerhof on fermentation , glycolysis , and muscle contraction . Based on prior research showing that "acetylcholine's actions on structural proteins" were responsible for nerve impulses, Nachmansohn and Machado investigated the origin of acetylcholine. An enzyme has been extracted from brain and nervous tissue which forms acetylcholine. The formation occurs only in presence of adenosinetriphosphate (ATP) . The enzyme
4828-457: Was a large part of the reason for Julius Axelrod ’s 1970 Nobel Prize in Physiology or Medicine (shared with Sir Bernard Katz and Ulf von Euler ). Classification of transferases continues to this day, with new ones being discovered frequently. An example of this is Pipe, a sulfotransferase involved in the dorsal-ventral patterning of Drosophila . Initially, the exact mechanism of Pipe
4899-524: Was approved for medical use in the United States in August 2020. Genetic testing , usually from blood samples, can be used to determine the precise nature and location of the DMD mutation in the dystrophin gene. It is known that these mutations cluster in areas known as the 'hot spot' regions — primarily in exons 45–53 and to a lesser extent exons 2–20. As the majority of DMD mutations occur in these 'hot spot' regions,
4970-532: Was later verified by the discovery of its reaction mechanism by Braunstein and Kritzmann in 1937. Their analysis showed that this reversible reaction could be applied to other tissues. This assertion was validated by Rudolf Schoenheimer 's work with radioisotopes as tracers in 1937. This in turn would pave the way for the possibility that similar transfers were a primary means of producing most amino acids via amino transfer. Another such example of early transferase research and later reclassification involved
5041-408: Was unknown, due to a lack of information on its substrate. Research into Pipe's catalytic activity eliminated the likelihood of it being a heparan sulfate glycosaminoglycan . Further research has shown that Pipe targets the ovarian structures for sulfation. Pipe is currently classified as a Drosophila heparan sulfate 2-O-sulfotransferase . Systematic names of transferases are constructed in
#259740