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Dehydrogenase24
  • In enzymology, a succinate-semialdehyde dehydrogenase [NAD(P)+] (EC 1.2.1.16) is an enzyme that catalyzes the chemical reaction succinate semialdehyde + NAD(P)+ + H2O ⇌ {\displaystyle \rightleftharpoons } succinate + NAD(P)H + 2 H+ The 4 substrates of this enzyme are succinate semialdehyde, NAD+, NADP+, and H2O, whereas its 4 products are succinate, NADH, NADPH, and H+. (wikipedia.org)
  • Other names in common use include succinate semialdehyde dehydrogenase (nicotinamide adenine, dinucleotide (phosphate)), and succinate-semialdehyde dehydrogenase [NAD(P)+]. This enzyme participates in 3 metabolic pathways: glutamate metabolism, tyrosine metabolism, and butanoate metabolism. (wikipedia.org)
  • 3 2 Under physiological hypoxia, low oxygen levels lead to reduced activity of succinate dehydrogenase (SDH), which metabolizes succinate, and other oxygen-dependent enzymes in the electron transport chain, causing succinate accumulation. (haematologica.org)
  • Following the formation of isocitrate there are four oxidation-reduction reactions, the first of which, the oxidative decarboxylation of isocitrate, is catalyzed by isocitrate dehydrogenase. (encyclopedia.com)
  • Succinate-Semialdehyde Dehydrogenase" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (harvard.edu)
  • This graph shows the total number of publications written about "Succinate-Semialdehyde Dehydrogenase" by people in Harvard Catalyst Profiles by year, and whether "Succinate-Semialdehyde Dehydrogenase" was a major or minor topic of these publication. (harvard.edu)
  • Below are the most recent publications written about "Succinate-Semialdehyde Dehydrogenase" by people in Profiles. (harvard.edu)
  • Molecular docking analysis for different enzymes involved in aging (collagenase, elastase and hyaluronidase), antioxidant enzymes (superoxide dismutase, glutathione-s-transferase, glutathione peroxidase and catalase) and mitochondrial enzymes (nicotinamide adenine dinucleotide (NAD)+hydrogen (H) dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and adenosine triphosphate synthase) was carried out for epigallocatechin gallate alone (1), withaferin A alone (2), epigallocatechin gallate and withaferin A in combination (3) and a reference molecule. (ijpsonline.com)
  • Learning Objectives Succinate dehydrogenase deficiency (type B) is associated with Pheochromocytoma-Paraganglioma syndrome, which can result in wide metastatic extra-adrenal paragangliomas. (snmjournals.org)
  • Pheocromocytoma-Paraganglioma syndromes are associated with mutations in 3 different genes that encode subunits B, C, and D of the mitochondrial enzyme succinate dehydrogenase (SDH), which catalyzes the oxidation of succinate to fumarate in the Krebs cycle [1-2]. (snmjournals.org)
  • Succinate dehydrogenase deficiency contributes to the predisposition to metastatic paragangliomas. (snmjournals.org)
  • The patient was identified with succinate dehydrogenase deficiency (type B), which is associated with Pheochromocytoma-Paraganglioma syndrome, Type 4, and can result in extra-adrenal paragangliomas which tend to metastasize widely. (snmjournals.org)
  • Subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). SDH1 and SDH2 form the catalytic dimer. (ymdb.ca)
  • Cloning and characterization of the iron-sulfur subunit gene of succinate dehydrogenase from Saccharomyces cerevisiae. (ymdb.ca)
  • Use of the DNA polymerase chain reaction for homology probing: isolation of partial cDNA or genomic clones encoding the iron-sulfur protein of succinate dehydrogenase from several species. (ymdb.ca)
  • Almost all of the enzymes of the citric acid cycle are soluble, with the single exception of the enzyme succinate dehydrogenase, which is embedded in the inner membrane of the mitochondrion. (ubooks.pub)
  • Pyruvate may be reduced to lactate in the cytoplasm or may be transported into the mitochondria for anabolic reactions, such as gluconeogenesis and lipogenesis, or for oxidation to acetyl CoA by the pyruvate dehydrogenase (PDH) complex (PDC). (bmj.com)
  • Complex II catalyzes the oxidation of succinate to fumarate (Succinate dehydrogenase: sdh) and transfers i. (bvsalud.org)
  • Succinate dehydrogenase inhibitors (SDHi) are fungicides used to control the proliferation of pathogenic fungi in crops. (bvsalud.org)
  • Their mode of action is based on blocking the activity of succinate dehydrogenase (SDH), a universal enzyme expressed by all species harboring mitochondria. (bvsalud.org)
  • Here, we show that succinate dehydrogenase (SDH) is required for maintenance of myocardial homeostasis of FAO/glycolysis. (bvsalud.org)
  • Succinate dehydrogenase B (SDHB), a mitochondrial gene, is related to the metabolic activities of cells and tissues throughout the body. (bvsalud.org)
  • SQR consists of a membrane-peripheral heterodimer domain (often called succinate dehydrogenase) which is tightly bound to a membrane-spanning anchor, which is a cytochrome with one or two heme groups depending on the organism. (lu.se)
  • However, the E. coli cells did not show increased succinate dehydrogenase activity nor did the operon complement a sdhCDAB defective E. coli mutant [7]. (lu.se)
Mitochondrial9
  • Here we propose that succinate has evolved as a signaling modality because its concentration reflects the coenzyme Q (CoQ) pool redox state, a central redox couple confined to the mitochondrial inner membrane. (nature.com)
  • Fig. 2: Succinate controls mitochondrial superoxide production through mitochondrial complex I. (nature.com)
  • Fig. 3: Accumulated mitochondrial succinate regulates cellular αKG-dependent dioxygenases. (nature.com)
  • SDH mutation caused enzymatic activity change in the mitochondrial electron transport chain can activate a hypoxic-angiogenic pathway with an accumulation of succinate and the transcription of a number of genes involved in tumorigenesis, angiogenesis, and resistance to apoptosis [1-2]. (snmjournals.org)
  • So, Shanta Dhar and colleagues from Sylvester Comprehensive Cancer Center at the University of Miami wanted to develop a therapy that would inhibit fatty acid oxidation in cancer cells by targeting a mitochondrial protein that is vital to the metabolic process, making the cells susceptible to cisplatin. (acs.org)
  • Pyruvate oxidation is the second step that occurs in the mitochondrial matrix of eukaryotes or the cytoplasm of prokaryotes. (stemcelldaily.com)
  • Determination of mitochondrial membrane potential has shown that in the presence of NADH-dependent substrates the membrane potential was dissipated by BHP but was completely restored after addition of succinate. (mitoeagle.org)
  • The SDH is involved in two interconnected metabolic processes for energy production: the transfer of electrons in the mitochondrial respiratory chain and the oxidation of succinate to fumarate in the Krebs cycle. (bvsalud.org)
  • Dicarboxylic aciduria and secondary impairment of long-chain fatty acid oxidation (LCFAO) may occur in mitochondrial disorders. (medscape.com)
NADH7
  • NADH and FADH 2 are coenzymes that accept the electrons released in oxidation reactions, and are utilized in oxidative phosphorylation . (citizendium.org)
  • NAD+ is then reduced to NADH and H+ during the final oxidation. (brighthub.com)
  • The oxidation of isocitrate is coupled with the reduction of NAD þ to NADH and the production of CO2. (encyclopedia.com)
  • Factor B produces several-fold stimulation of ATP-driven Nad reduction, and of net phosphorylation coupled to Nadh or succinate oxidation in ammonia particles. (eurekamag.com)
  • Reducing equivalents (NADH, FADH 2 ) are generated by reactions catalysed by the PDC and the tricarboxylic acid cycle and donate electrons (e - ) that enter the respiratory chain at NADH ubiquinone oxidoreductase (complex I) or at succinate ubiquinone oxidoreductase (complex II). (bmj.com)
  • Ethanol is a most efficient reduced substrate (as ED) because its biooxidation can provide energy (ATP) and reducing equivalents (NADH), and acetyl-CoA to drive the reverse β-oxidation for chain elongation. (biomedcentral.com)
  • Lactate has also been described to generate the acetyl-CoA to provide the two carbon atoms for the acetate to n -butyrate elongation via reverse β-oxidation, in which the oxidation of lactate to pyruvate produces NADH and the conversion of pyruvate to acetyl-CoA with ATP generation. (biomedcentral.com)
Pyruvate4
Citric acid4
  • In many tissues, especially heart tissue, fatty acids are broken down through a process known as beta oxidation which results in acetyl-CoA which can be used in the citric acid cycle. (citizendium.org)
  • Among these, the citric acid cycle intermediate succinate stands out owing to its multiple roles in disparate pathways, its dramatic concentration changes and its selective cell release. (nature.com)
  • If this transfer does not occur, the oxidation steps of the citric acid cycle also do not occur. (ubooks.pub)
  • Succinate:quinone oxidoreductase (SQR) is both a Krebs´ citric acid cycle enzyme and a component (Complex II) of the respiratory chain in aerobic cells. (lu.se)
Krebs3
  • Murphy, M. P. & O'Neill, L. A. J. Krebs cycle reimagined: the emerging roles of succinate and itaconate as signal transducers. (nature.com)
  • The enzymatic steps of glycolysis and the subsequent synthesis of acetyl-CoA involve a linear sequence, whereas the oxidation of acetyl-CoA in the Krebs cycle is a cyclic sequence of reactions in which the starting substrate is subsequently regenerated with each turn of the cycle. (encyclopedia.com)
  • Krebs cycle metabolites and preferential succinate oxidation following neonatal hypoxic-ischemic brain injury in mice. (cornell.edu)
GLUTAMATE2
  • An enzyme that plays a role in the GLUTAMATE and butanoate metabolism pathways by catalyzing the oxidation of succinate semialdehyde to SUCCINATE using NAD+ as a coenzyme. (harvard.edu)
  • Their oxygen consumption rates with succinate plus glutamate as substrates were measured with an oxygen electrode at ambient temperatures between 18-55°C. 3. (bgu.ac.il)
Glycolysis7
  • Nonetheless, when cells rely on anaerobic glycolysis, like cancer cells and certain innate immune cells upon activation, other metabolic pathways sustain succinate levels, including glutamine-dependent anerplerosis to α-ketoglutarate, and eventually citrate by reductive carboxylation. (haematologica.org)
  • Previously, researchers have shown in mouse models that as the disease advances, tumor cells shift from glycolysis toward fatty acid oxidation to support their growth and division. (acs.org)
  • In glycolysis, what removes electrons during oxidation? (medicoholic.com)
  • A hallmark of heart failure is a metabolic switch away from fatty acids ß-oxidation (FAO) to glycolysis. (bvsalud.org)
  • Succinate induced DNA hypermethylation and depressed the expression of FAO genes in myocardium, leading to imbalanced FAO/glycolysis. (bvsalud.org)
  • The authors found that the aerobic oxidation of glucose was reduced, and the anaerobic glycolysis was significantly enhanced in the myocardium in the early stage of CPR. (dirjournal.org)
  • The rate of aerobic oxidation of free fatty acids and glucose in cardiomyocytes is decreased, yet the rate of anaerobic glycolysis is enhanced. (dirjournal.org)
Oxidoreductase2
  • The systematic name of this enzyme class is succinate-semialdehyde:NAD(P)+ oxidoreductase. (wikipedia.org)
  • Complex II (Succinate-ubiquinone oxidoreductase) is an importnat enzyme complex for the tricarboxylic acid cycle and the aerobic respiratory chain of motochondria and procaryotic organisms (12, 24). (bvsalud.org)
Mitochondria3
  • Succinate, by equilibrating with the CoQ pool, enables the status of this central bioenergetic parameter to be communicated from mitochondria to the rest of the cell, into the circulation and to other cells. (nature.com)
  • Dicarboxylate carriers (DIC) and voltage-dependent anion channels (VDAC) control succinate release from mitochondria to cytosol. (haematologica.org)
  • The addition of carbonyl- cyanide -m- chlorophenylhydrazone to H2O2 or untreated mitochondria resulted in an increase in oxygen consumption in the presence of succinate. (cdc.gov)
Fumarate3
  • Fumarate is then formed through the oxidation of the succinate. (brighthub.com)
  • and Lovley, DR, "Genetic characterization of a single bifunctional enzyme for fumarate reduction and succinate oxidation in Geobacter sulfurreducens and engineering of fumarate reduction in Geobacter metallireducens" (2006). (umass.edu)
  • The enzyme has a central role in carbon and energy metabolism by catalyzing the oxidation of succinate to form fumarate coupled to the reduction of quinone in the respiratory chain. (lu.se)
Accumulation3
  • Accumulation of succinate associates with succinylation, i.e. addition of succinyl group to a lysine residue of a protein. (haematologica.org)
  • The cellular and molecular mechanisms related to such genetic inactivation have been well described in neuroendocrine tumors, in which it induces an oxidative stress, a pseudohypoxic phenotype, a metabolic, epigenetic and transcriptomic remodeling, and alterations in the migration and invasion capacities of cancer cells, in connection with the accumulation of succinate, an oncometabolite, substrate of the SDH. (bvsalud.org)
  • SDH-deficient hearts exhibited an increase in genome-wide DNA methylation associated with accumulation of succinate, a metabolite known to inhibit DNA demethylases, resulting in changes of myocardial transcriptomic landscape. (bvsalud.org)
Metabolites2
  • Energy resources including glucose, glutamine, free fatty acids, and other metabolites such as succinate largely alter the functions of macrophages, neutrophils, and T cells. (wjgnet.com)
  • In addition, aerobic glucose oxidation metabolites were significantly increased ( P P (dirjournal.org)
Coenzyme3
  • The fourth step involves carbon dioxide being taken out again, the oxidation of the alpha-ketoglutarate, and the adding of coenzyme A. Succinyl-CoA, a four-carbon compound is then formed. (brighthub.com)
  • Succinate is produced by taking away the coenzyme A from succinyl-CoA. (brighthub.com)
  • The metabolite succinate or succinic acid is at the hub of the tricarboxylic acid (TCA) cycle, and it is mainly produced by succinyl coenzyme A synthetase from succinyl coenzyme A, in a reversible reaction that generally occurs under aerobic conditions ( Figure 1 ). (haematologica.org)
Alpha-ketoglutarate1
  • Simultaneously, the authors also tested the expression levels of the total adenosine triphosphate (ATP) and the key intermediate products of glucose ovidation as alpha ketoglutarate, citrate, and succinate in the myocardium. (dirjournal.org)
Glucose oxidation1
Anaerobic conditions1
  • Succinate is an intermediate of several metabolic pathways, i.e. tricarboxylic acid (TCA) cycle under normoxic conditions (blue lines), and glutamine-dependent anerplerosis and γ-aminobutyric acid (GABA) shunt under anaerobic conditions (red lines). (haematologica.org)
Metabolic2
  • The cisplatin prodrug Platin-L, which has a cisplatin molecule bound to a 12-carbon fatty acid on one side and succinate on the other side, had the greatest effect by binding to a key protein required for long chain fatty acid transport, a primary step in this metabolic process. (acs.org)
  • Inhibition of succinate by α-ketoglutarate restored transcriptional profiles and metabolic disorders in SDH-deficient cardiomyocytes. (bvsalud.org)
Citrate1
  • Succinate is released to the extracellular space through sodium-coupled citrate transporters (SLC13). (haematologica.org)
Fatty3
  • FAO: Fatty acid oxidation. (wjgnet.com)
  • The researchers verified that human prostate cancer cells thrive using fatty acid oxidation by assessing the biopsies of 38 people with the disease. (acs.org)
  • Then they screened several cisplatin-containing prodrug compounds, which release the platinum-based molecule when they're broken down, to see if they could inhibit fatty acid oxidation. (acs.org)
Intermediate1
  • Succinate is an essential intermediate of the tricarboxylic acid cycle that exerts pleiotropic roles beyond metabolism in both physiological and pathological conditions. (haematologica.org)
Dioxygenases1
  • Succinate further inhibits several dioxygenases involved in epigenetic regulation like ten-eleven translocation methylcytosine dioxygenase (TET) and jumonji C domain-containing histone lysine demethylases (JMJD3). (haematologica.org)
Acetyl1
  • The carbon atom of the methyl group of acetyl-CoA is very resistant to chemical oxidation, and under ordinary circumstances, the reaction would require very harsh conditions, incompatible with the cellular environment, to oxidize the carbon atoms of acetyl-CoA to CO2. (encyclopedia.com)
Metabolism1
  • Hence, succinate links metabolism to processes like gene expression and intercellular communication. (haematologica.org)
Pathway1
  • 1 Similarly, succinate may derive from the γ-aminobutyric acid shunt pathway that correlates with levels of expression of the γ-aminobutyric acid transporters solute carrier family 6 members 12 and 13 (SLC6A12, SLC6A13). (haematologica.org)
Impairment1
  • Hepatic Impairment: Consider initiating metoprolol succinate therapy at low doses and gradually increase dosage to optimize therapy, while monitoring closely for adverse events. (nih.gov)
Bound1
Oxoglutarate1
  • Strong inhibitory effect at low concentrations of BHP (15-30 microM) was found for oxoglutarate and palmitoyl carnitine oxidation. (mitoeagle.org)
Physiology2
  • Fig. 4: pH-gated succinate secretion regulates systemic physiology. (nature.com)
  • The peak values of delta psi and ROS generation are under succinate oxidation and delta psi is modified using either an uncoupler or complex II inhibitor, so, as so often, we are a long way from physiology here but the general principle that ROS generation rises rapidly above a threshold delta psi appears to hold good today. (blogspot.com)
Protein1
  • GPR91 is a G protein-coupled cell surface receptor for extracellular succinate (Sucnr1). (haematologica.org)
Cellular1
  • Interestingly, succinate plays key dual roles during inflammatory responses, leading to net inflammation or anti-inflammation depending on factors like the cellular context. (haematologica.org)
Roles1
  • The logic of this form of regulation explains many emerging roles of succinate in biology, and suggests future research questions. (nature.com)
Cancer1
  • 6 3 In fact, one of the first pieces of evidence for a role of succinate in cancer development was provided by the discovery of pseudohypoxia, which refers to activation of hypoxia signaling pathways under normal oxygen levels. (haematologica.org)
Show1
  • Our data also show that succinate could be an important nutritional substrate protecting hepatocytes during peroxidative damage. (mitoeagle.org)
Release3
  • These highlights do not include all the information needed to use METOPROLOL SUCCINATE EXTENDED-RELEASE TABLETS safely and effectively. (nih.gov)
  • Switching from immediate-release metoprolol to metoprolol succinate extended-release tablets: use the same total daily dose of metoprolol succinate extended-release tablets. (nih.gov)
  • Metoprolol succinate extended-release tablets are indicated for the treatment of hypertension, to lower blood pressure. (nih.gov)
Steps1
  • Figure 1 summarises the major steps of carbohydrate oxidation in mammalian cells. (bmj.com)
Functions1
  • 5 4 Succinate functions as a competitive inhibitor for prolyl hydroxylase domain (PHD) proteins that are central to degradation of hypoxia-inducible factor (HIF)-1α subunit. (haematologica.org)
Production2