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36-680: SDH may refer to: Biology and medicine [ edit ] Serine dehydratase Sorbitol dehydrogenase L-sorbose 1-dehydrogenase Subdural haematoma Succinate dehydrogenase Organizations and places [ edit ] St David's Hall Social Democrats of Croatia Society for Digital Humanities Sydney Dental Hospital Transportation [ edit ] Sudbury Hill Harrow railway station , England, National Rail station code Other [ edit ] Shubnikov–de Haas effect Social Determinants of Health Southern Kurdish , by ISO 639-3 code Subtitles for

72-416: A coenzyme in all transamination reactions, and in certain decarboxylation , deamination , and racemization reactions of amino acids . The aldehyde group of PLP forms a Schiff-base linkage (internal aldimine ) with the ε-amino group of a specific lysine group of the aminotransferase enzyme. The α-amino group of the amino acid substrate displaces the ε-amino group of the active-site lysine residue in

108-497: A phosphoric acid. Several inhibitors of PLP enzymes are known. One type of inhibitor forms an electrophile with PLP, causing it to irreversibly react with the active site lysine. Acetylenic compounds (e.g. propargylglycine) and vinylic compounds (e.g. vinylglycine) are such inhibitors. A different type of inhibitor inactivates PLP, and such are α-methyl and amino-oxy substrate analogs (e.g. α-methylglutamate). Still other inhibitors have good leaving groups that nucleophilically attack

144-414: A process known as transaldimination. The resulting external aldimine can lose a proton, carbon dioxide, or an amino acid sidechain to become a quinonoid intermediate, which in turn can act as a nucleophile in several reaction pathways. In transamination, after deprotonation the quinonoid intermediate accepts a proton at a different position to become a ketimine . The resulting ketimine is hydrolysed so that

180-467: A step catalyzed by PLP-synthase, an enzyme composed of two subunits. PdxS catalyzes the condensation of ribulose 5-phosphate, glyceraldehyde-3-phosphate, and ammonia , this latter molecules is produced by PdxT which catalyzes the production of ammonia from glutamine . PdxS is a (β/α)8 barrel (also known as a TIM-barrel) that forms a dodecamer. The widespread utilization of PLP in central metabolism, especially in amino acid biosynthesis, and its activity in

216-461: Is pyridoxine 5'-phosphate . The condensation is catalyzed by PNP synthase , encoded by pdxJ , which creates PNP (pyridoxine 5' phosphate). The final enzyme is PNP oxidase ( pdxH ), which catalyzes the oxidation of the 4' hydroxyl group to an aldehyde using dioxigen, resulting in hydrogen peroxide. The first branch is catalyzed in E. coli by enzymes encoded by epd , pdxB , serC and pdxA . These share mechanistical similarities and homology with

252-441: Is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent activities, corresponding to ~4% of all classified activities. The versatility of PLP arises from its ability to covalently bind the substrate, and then to act as an electrophilic catalyst, thereby stabilizing different types of carbanionic reaction intermediates. PLP acts as

288-436: Is a precursor to polyamines. Pyridoxal phosphate has numerous roles in human body. A few examples below: PLP is also found on glycogen phosphorylase in the liver, where it is used to break down glycogen in glycogenolysis when glucagon or epinephrine signals it to do so. However, this enzyme does not exploit the reactive aldehyde group, but instead utilizes the phosphate group on PLP to perform its reaction. Although

324-492: Is an example of such an enzyme. Human Serine hydroxymethyltransferase 2 regulates one-carbon transfer reactions required for amino acid and nucleotide metabolism, and exists in dimeric and tetrameric forms. The dimeric SHMT2 variant is a potent inhibitor of the BRISC deubiquitylase enzyme complex, which regulates immune-based cell signaling. Recent studies show that SJMT2 tetramerization is induced by PLP. This prevents interaction with

360-623: Is augmented by high-protein diets and starvation. During periods of low carbohydrates , serine is converted into pyruvate via SDH. This pyruvate enters the mitochondria where it can be converted into oxaloacetate , and, thus, glucose. Little is known about the properties and the function of human SDH because human liver has low SDH activity. In a study done by Yoshida and Kikuchi, routes of glycine breakdown were measured. Glycine can be converted into serine and either become pyruvate via serine dehydratase or undergo oxidative cleavage into methylene-THF , ammonia , and carbon dioxide. Results showed

396-496: Is different from Wikidata All article disambiguation pages All disambiguation pages Serine dehydratase This enzyme has one substrate , L -serine , and two products , pyruvate and NH 3 , and uses one cofactor , pyridoxal phosphate (PLP). The enzyme's main role is in gluconeogenesis in the liver's cytoplasm . Serine Dehydratase is also known as: The holoenzyme SDH contains 319 residues , one PLP cofactor molecule. The overall fold of

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432-466: Is generated, commonly referred to as the external aldimine. After this step, the pathway for each PLP-catalyzed reactions diverge. Specificity is conferred by the fact that, of the four bonds of the alpha-carbon of the amino acid aldimine state, the bond perpendicular to the pyridine ring will be broken ( Dunathan Stereoelectronic Hypothesis ). Consequently, specificity is dictated by how the enzymes bind their substrates. An additional role in specificity

468-437: Is hydrogen-bonded to the side chain of Asn 67, and the phosphate group of PLP is coordinated by main chain amides from the tetraglycine loop. (Figure 3 and Figure 4). The reaction catalyzed by serine dehydratase follows the pattern seen by other PLP-dependent reactions. A Schiff base linkage is made and the aminoacrylate group is released which undergoes non-enzymatic hydrolytic deamination to pyruvate . According to

504-450: Is known to accelerate glycolysis and repress induction of liver serine dehydratase in adult diabetic rats. Studies have been conducted to show insulin causes a 40-50% inhibition of the induction serine dehydratase by glucagon in hepatocytes of rats. Studies have also shown that insulin and epinephrine inhibit Serine Dehydratase activity by inhibiting transcription of the SDH gene in

540-413: Is played by the ease of protonation of the pyridine ring nitrogen. PLP is retained in the active site not only thanks to the lysine, but also thanks to the interaction of the phosphate group and a phosphate binding pocket and to a lesser extent thanks to base stacking of the pyridine ring with an overhanging aromatic residue, generally tyrosine (which may also partake in the acid–base catalysis). Despite

576-474: Is synthesized from pyridoxal by the enzyme pyridoxal kinase , requiring one ATP molecule. PLP is metabolized in the liver. Two natural pathways for PLP are currently known: one requires deoxyxylulose 5-phosphate (DXP), while the other does not, hence they are known as DXP-dependent and DXP-independent. These pathways have been studied extensively in Escherichia coli and Bacillus subtilis , respectively. Despite

612-517: The monomer is very similar to that of other PLP-dependent enzymes of the Beta-family. The enzyme contains a large catalytic domain that binds PLP and a small domain. The domains are linked by two residues 32-35 and 138-146, with the internal gap created being the space for the active site The PLP cofactor is positioned in between the Beta-strands 7 and 10 of the large domain and lies on

648-460: The BRISC deubiqutylase complex, potentially linking vitamin B6 levels and metabolism to inflammation. The pyridoxal-5′-phosphate-dependent enzymes (PLP enzymes) catalyze myriad reactions. Although the scope of PLP-catalyzed reactions appears to be immense, the unifying principle is the formation of an internal lysine-derived aldimine. Once the amino substrate interacts with the active site, a new Schiff base

684-525: The PLP. Such is chloroalanine , which inhibits a large number of enzymes. Examples of inhibitors: Pyridoxal-5-phosphate (vitamin B6) -dependent enzymes have multiple evolutionary origins. The overall B6 enzymes diverged into four independent evolutionary lines: α family (i.e. aspartate aminotransferase ), β family ( serine dehydratase ),D- alanine aminotransferase family and the alanine racemase family. An example of

720-457: The absence of enzymes, suggests PLP may be a "prebiotic" compound—that is, one that predates the origin of organic life (not to be confused with prebiotic compounds , substances which serve as a food source for beneficial bacteria). In fact, heating NH3 and Glycolaldehyde spontaneously forms a variety of pyridines, including pyridoxal. Under certain conditions, PLP is formed from cyanoacetylene, diacetylene, carbon monoxide, hydrogen, water, and

756-451: The amino group remains on the complex. In addition, PLP is used by aminotransferases (or transaminases) that act upon unusual sugars such as perosamine and desosamine . In these reactions, the PLP reacts with glutamate , which transfers its alpha-amino group to PLP to make pyridoxamine phosphate (PMP). PMP then transfers its nitrogen to the sugar, making an amino sugar . PLP is also involved in various beta-elimination reactions such as

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792-515: The deaf and hard-of-hearing Synchronous digital hierarchy , in telecommunications Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title SDH . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=SDH&oldid=1215390817 " Category : Disambiguation pages Hidden categories: Short description

828-535: The disparity in the starting compounds and the different number of steps required, the two pathways possess many commonalities. The DXP-dependent biosynthetic route requires several steps and a convergence of two branches, one producing 3-hydroxy-1-aminoacetone phosphate from erythrose 4-phosphate , while the other (single enzyme) producing deoxyxylulose 5-phosphate (DXP) from glyceraldehyde 3-phosphate (GAP) and pyruvate . The condensation product of 3-hydroxy-1-aminoacetone phosphate and deoxyxylulose 5-phosphate

864-429: The hepatocytes. Similarly, increasing levels of glucagon , increase the activity of SDH because this hormone up-regulates the SDH enzyme. This makes sense in the context of gluconeogenesis . The main role of SDH is to create pyruvate that can be converted into free glucose. And glucagon gives the signal to repress gluconeogenesis and increase the amount of free glucose in the blood by releasing glycogen stores from

900-473: The large internal gap made between small and large domain. The cofactor is covalently bonded through a Schiff base linkage to Lys41 . The cofactor is sandwiched between the side chain of Phe 40 and the main chain of Ala222 . Each of the polar substituents of PLP is coordinated by functional groups: the pyridinium nitrogen of PLP is hydrogen-bonded to the side chain of Cys 303, the C3-hydroxyl group of PLP

936-446: The limited requirements for a PLP binding pocket, PLP enzymes belong to only five different families. These families do not correlate well with a particular type of reaction. The five families are classified as fold types followed by a Roman numeral. Animals are auxotroph for this enzyme co-factor and require it or an intermediate to be supplemented, hence its classification as a vitamin B 6 , unlike MoCo or CoQ10 for example. PLP

972-648: The liver. Homocysteine , a compound that SDH combines with Serine to create cystathionine , also noncompetitively inhibits the action of SDH. Studies have shown that homocysteine reacts with SDH's PLP coenzyme to create a complex. This complex is devoid of coenzyme activity and SDH is not able to function (See Enzyme Mechanism Section). In general, homocysteine is an amino acid and metabolite of methionine ; increased levels of homocysteine can lead to homocystinuria (see section Disease Relevance). In general, SDH levels decrease with increasing mammalian size. SDH enzyme plays an important role in gluconeogenesis. Activity

1008-424: The reactions carried out by serine dehydratase and GDP-4-keto-6-deoxymannose-3-dehydratase (ColD) . It is also active in the condensation reaction in heme synthesis. PLP plays a role in the conversion of levodopa into dopamine , facilitates the conversion of the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter GABA , and allows SAM to be decarboxylated to form propylamine , which

1044-426: The secondary importance of the SDH pathway. SDH may be significant in the development of hyperglycemia and tumors. Nonketotic hyperglycemia is due to the deficiency of threonine dehydratase , a close relative of serine dehydratase. Serine dehydratase has also been found to be absent in human colon carcinoma and rat sarcoma . The observed enzyme imbalance in these tumors shows that an increased capacity for

1080-507: The series of assays performed by Cleland (1967), the linear rate of pyruvate formation at various concentrations of inhibitors demonstrated that L- cysteine and D- serine competitively inhibit the enzyme SDH. The reason that SDH activity is inhibited by L-cysteine is because an inorganic sulfur is created from L- Cysteine via Cystine Desulfrase and sulfur-containing groups are known to promote inhibition. L-threonine competitively inhibits Serine Dehydratase as well. Moreover, insulin

1116-514: The synthesis of serine is coupled to its utilization for nucleotide biosynthesis as a part of the commitment to cellular replication in cancer cells. This pattern is found in sarcomas and carcinomas , and in tumors of human and rodent origin. Human and rat serine dehydratase cDNA are identical except for a 36 amino acid residue stretch. Similarities have also been shown between yeast and E. coli threonine dehydratase and human serine dehydratase. Human SDH shows sequence homology of 27% with

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1152-409: The three enzymes in serine biosynthesis ( serA (homologue of pdxB ), serC , serB — however, epd is a homologue of gap ), which points towards a shared evolutionary origin of the two pathways. In several species there are two homologues of the E. coli serC gene, generally one in a ser operon ( serC ), and the other in a pdx operon, in which case it is called pdxF . A "serendipitous pathway"

1188-415: The vast majority of PLP-dependent enzymes form an internal aldimine with PLP via an active site lysine residue, some PLP-dependent enzymes do not have this lysine residue, but instead have a histidine in the active site. In such a case, the histidine cannot form the internal aldimine, and, therefore, the co-factor does not become covalently tethered to the enzyme. GDP-4-keto-6-deoxymannose-3-dehydratase (ColD)

1224-407: The yeast enzyme and 27% with the E. coli enzyme. Overall PLP enzymes exhibit high conservation of the active site residues. (See Template:Leucine metabolism in humans – this diagram does not include the pathway for β-leucine synthesis via leucine 2,3-aminomutase) Pyridoxal phosphate Pyridoxal phosphate ( PLP , pyridoxal 5'- phosphate , P5P ), the active form of vitamin B 6 ,

1260-408: Was dephosphorylated, resulting in an unstable intermediate that decarboxylates spontaneously (hence the presence of the phosphate in the serine biosynthetic pathway) to glycaldehyde. Glycaldehyde was condensed with glycine and the phosphorylated product was 4-phosphohydroxythreonine (4PHT), the canonical substrate for 4-PHT dehydrogenase ( pdxA ). The DXP-independent PLP-biosynthetic route consists of

1296-443: Was found in an overexpression library that could suppress the auxotrophy caused by the deletion of pdxB (encoding erythronate 4 phosphate dehydrogenase) in E. coli . The serendipitous pathway was very inefficient, but was possible due to the promiscuous activity of various enzymes. It started with 3-phosphohydroxypyruvate (the product of the serA -encoded enzyme in serine biosynthesis) and did not require erythronate-4-phosphate. 3PHP

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