Pages in category "Glycolysis"
The following 38 pages are in this category, out of 38 total. This list may not reflect recent changes (learn more).
The following 38 pages are in this category, out of 38 total. This list may not reflect recent changes (learn more).
1. Glycolysis – Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+. The free energy released in this process is used to form the high-energy molecules ATP, glycolysis is a determined sequence of ten enzyme-catalyzed reactions. The intermediates provide entry points to glycolysis, for example, most monosaccharides, such as fructose and galactose, can be converted to one of these intermediates. The intermediates may also be directly useful, for example, the intermediate dihydroxyacetone phosphate is a source of the glycerol that combines with fatty acids to form fat. Glycolysis is an oxygen independent metabolic pathway, meaning that it not use molecular oxygen for any of its reactions. However the products of glycolysis are sometimes metabolized using atmospheric oxygen, when molecular oxygen is used for the metabolism of the products of glycolysis the process is usually referred to as aerobic, whereas if no oxygen is used the process is said to be anaerobic. Thus, glycolysis occurs, with variations, in all organisms. The wide occurrence of glycolysis indicates that it is one of the most ancient metabolic pathways, glycolysis could thus have originated from chemical constraints of the prebiotic world. Glycolysis occurs in most organisms in the cytosol of the cell, the most common type of glycolysis is the Embden–Meyerhof–Parnas, which was discovered by Gustav Embden, Otto Meyerhof, and Jakub Karol Parnas. Glycolysis also refers to other pathways, such as the Entner–Doudoroff pathway, however, the discussion here will be limited to the Embden–Meyerhof–Parnas pathway. The overall reaction of glycolysis is, The use of symbols in this equation makes it appear unbalanced with respect to oxygen atoms, hydrogen atoms, and charges. In the cellular environment, all three groups of ADP dissociate into −O− and H+, giving ADP3−, and this ion tends to exist in an ionic bond with Mg2+. ATP behaves identically except that it has four groups, giving ATPMg2−. When these differences along with the charges on the two phosphate groups are considered together, the net charges of −4 on each side are balanced. For simple fermentations, the metabolism of one molecule of glucose to two molecules of pyruvate has a net yield of two molecules of ATP, most cells will then carry out further reactions to repay the used NAD+ and produce a final product of ethanol or lactic acid. Many bacteria use inorganic compounds as hydrogen acceptors to regenerate the NAD+, cells performing aerobic respiration synthesize much more ATP, but not as part of glycolysis. These further aerobic reactions use pyruvate and NADH + H+ from glycolysis, the pathway of glycolysis as it is known today took almost 100 years to fully discover. The combined results of many experiments were required in order to understand the pathway as a whole
2. Aldolase A – Aldolase A, also known as fructose-bisphosphate aldolase, is an enzyme that in humans is encoded by the ALDOA gene on chromosome 16. The protein encoded by this gene is an enzyme that catalyzes the reversible conversion of fructose-1, 6-bisphosphate to glyceraldehyde 3-phosphate. Three aldolase isozymes, encoded by three different genes, are expressed during development. Aldolase A is found in the embryo and is produced in even greater amounts in adult muscle. Aldolase A expression is repressed in adult liver, kidney and intestine and similar to aldolase C levels in brain, aldolase A deficiency has been associated with myopathy and hemolytic anemia. Alternative splicing and alternative promoter usage results in transcript variants. Related pseudogenes have been identified on chromosomes 3 and 10, ALDOA is a homotetramer and one of the three aldolase isozymes, encoded by three different genes. The ALDOA gene contains 8 exons and the 5 UTR IB, key amino acids responsible for its catalytic function have been identified. Residue Glu187 participates in multiple functions, including FBP aldolase catalysis, acid–base catalysis during substrate binding, dehydration, though ALDOA localizes to the nucleus, it lacks any known nuclear localization signals. In mammalian aldolase, the key amino acid residues involved in the reaction are lysine and tyrosine. The tyrosine acts as an efficient hydrogen acceptor while the lysine covalently binds, many bacteria use two magnesium ions in place of the lysine. Compound C05378 at KEGG Pathway Database, enzyme 188.8.131.52 at KEGG Pathway Database. Compound C00111 at KEGG Pathway Database, compound C00118 at KEGG Pathway Database. The numbering of the carbon atoms indicates the fate of the according to their position in fructose 6-phosphate. ALDOA is a key enzyme in the step of glycolysis. It catalyzes the conversion of fructose-1, 6-bisphosphate to glyceraldehydes-3-phosphate. As a result, it is a player in ATP biosynthesis. ALDOA likely regulates actin cytoskeleton remodeling through interacting with cytohesin-2 and Arf6, ALDOA is ubiquitously expressed in most tissues, though it is predominantly expressed in developing embryo and adult muscle
3. Aldolase B – In mammals, aldolase B is preferentially expressed in the liver, while aldolase A is expressed in muscle and erythrocytes and aldolase C is expressed in the brain. Slight differences in isozyme structure result in different activities for the two molecules, FBP and fructose 1-phosphate. Aldolase B exhibits no preference and thus catalyzes both reactions, while aldolases A and C prefer FBP, in humans, aldolase B is encoded by the ALDOB gene located on chromosome 9. The gene is 14,500 base pairs long and contains 9 exons, defects in this gene have been identified as the cause of hereditary fructose intolerance. The generic fructose bisphosphate aldolase enzyme cleaves a 6-carbon fructose sugar into two 3-carbon products in an aldol reaction. After Schiff base formation, the hydroxyl group on the fructose backbone is then deprotonated by an aspartate residue. Schiff base hydrolysis yields two 3-carbon products, depending on the reactant, F1P or FBP, the products are DHAP and glyceraldehyde or glyceraldehyde 3-phosphate, respectively. The ΔG°’ of this reaction is +23.9 kJ/mol, though the reaction may seem too uphill to occur, it is of note that under physiological conditions, the ΔG of the reaction falls to close to or below zero. For example, the ΔG of this reaction under physiological conditions in erythrocytes is -0.23 kJ/mol, click on genes, proteins and metabolites below to link to respective articles. Aldolase B is an enzyme, composed of four subunits with molecular weights of 36 kDa with local 222 symmetry. Each subunit has a weight of 36 kDa and contains an eight-stranded α/β barrel. Such regions have been denoted isozyme-specific regions and these regions are thought to give isozymes their specificities and structural differences. ISRs 1-3 are all found in exon 3 of the ALDOB gene, ISR4 is the most variable of the four and is found at the c-terminal end of the protein. ISRs 1-3 are found predominantly in patches on the surface of the enzyme and these patches do not overlap with the active site, indicating that ISRs may change specific isozyme substrate specificity from a distance or cause the C-terminus interactions with the active site. A recent theory suggests that ISRs may allow for different conformational dynamics in the enzyme that account for its specificity. Aldolase B plays a key role in metabolism as it catalyzes one of the major steps of the glycolytic-gluconeogenic pathway. Though it does catalyze the breakdown of glucose, it plays an important role in fructose metabolism, which occurs mostly in the liver, renal cortex. When fructose is absorbed, it is phosphorylated by fructokinase to form fructose 1-phosphate, aldolase B then catalyzes F1P breakdown into glyceraldehyde and DHAP
4. Alpha-enolase – Enolase 1, more commonly known as alpha-enolase, is a glycolytic enzyme expressed in most tissues, one of the isozymes of enolase. Each isoenzyme is a composed of 2 alpha,2 gamma, or 2 beta subunits. Alpha-enolase, in addition, functions as a structural protein in the monomeric form. Alternative splicing of this results in a shorter isoform that has been shown to bind to the c-myc promoter. Several pseudogenes have been identified, including one on the arm of chromosome 1. Alpha-enolase has also identified as an autoantigen in Hashimoto encephalopathy. ENO1 is one of three isoforms, the other two being ENO2 and ENO3. Each isoform is a subunit that can hetero- or homodimerize to form αα, αβ, αγ, ββ. The ENO1 gene spans 18 kb and lacks a TATA box while possessing multiple transcription start sites, a hypoxia-responsive element can be found in the ENO1 promoter and allows the enzyme to function in aerobic glycolysis and contribute to the Warburg effect in tumor cells. The mRNA transcript of the ENO1 gene can be translated into a cytoplasmic protein, with a molecular weight of 48 kDa, or a nuclear protein. The nuclear form was identified as Myc-binding protein-1, which downregulates the protein level of the c-myc protooncogene. A start codon at codon 97 of ENO1 and a Kozak consensus sequence were found preceding the 3 region of ENO1 encoding the MBP1 protein, in addition, the N-terminal region of the MBP1 protein it critical to DNA binding and, thus, its inhibitory function. As an enolase, ENO1 is a glycolytic enzyme the catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate and this isozyme is ubiquitously expressed in adult human tissues, including liver, brain, kidney, and spleen. Within cells, ENO1 predominantly localizes to the cytoplasm, though an alternatively translated form is localizes to the nucleus, in many of these tumors, ENO1 promoted cell proliferation by regulating the PI3K/AKT signaling pathway and induced tumorigenesis by activating plasminogen. Moreover, ENO1 is expressed on the cell surface during pathological conditions such as inflammation, autoimmunity. Its role as a receptor leads to extracellular matrix degradation. Due to its expression, targeting surface ENO1 enables selective targeting of tumor cells while leaving the ENO1 inside normal cells functional. Considering these factors, ENO1 holds great potential to serve as a therapeutic target for treating many types of tumors in patients
5. 1,3-Bisphosphoglyceric acid – 1, 3-Bisphosphoglyceric acid is a 3-carbon organic molecule present in most, if not all, living organisms. It primarily exists as an intermediate in both glycolysis during respiration and the Calvin cycle during photosynthesis. 1, 3BPG is a stage between glycerate 3-phosphate and glyceraldehyde 3-phosphate during the fixation/reduction of CO2. 1, 3BPG is also a precursor to 2, 3-bisphosphoglycerate which in turn is an intermediate in the glycolytic pathway. 1, 3-Bisphosphoglycerate is the base of 1, 3-bisphosphoglyceric acid. It is phosphorylated at the number 1 and 3 carbons, the result of this phosphorylation gives 1, 3BPG important biological properties such as the ability to phosphorylate ADP to form the energy storage molecule ATP. Compound C00118 at KEGG Pathway Database, enzyme 184.108.40.206 at KEGG Pathway Database. Compound C00236 at KEGG Pathway Database, enzyme 220.127.116.11 at KEGG Pathway Database. Compound C00197 at KEGG Pathway Database, as previously mentioned 1, 3BPG is a metabolic intermediate in the glycolytic pathway. It is created by the oxidation of the aldehyde in G3P. The result of oxidation is the conversion of the aldehyde group into a carboxylic acid group which drives the formation of an acyl phosphate bond. This is incidentally the only step in the pathway in which NAD+ is converted into NADH. The formation reaction of 1, 3BPG requires the presence of an enzyme called glyceraldehyde-3-phosphate dehydrogenase, the high-energy acyl phosphate bond of 1, 3BPG is important in respiration as it assists in the formation of ATP. The molecule of ATP created during the reaction is the first molecule produced during respiration. This is as a result of one acyl phosphate bond being cleaved whilst another is created and this reaction is not naturally spontaneous and requires the presence of a catalyst. This role is performed by the enzyme phosphoglycerate kinase, during the reaction phosphoglycerate kinase undergoes a substrate induced conformational change similar to another metabolic enzyme called hexokinase. Glycolysis also uses two molecules of ATP in its initial stages as a committed and irreversible step, for this reason glycolysis is not reversible and has a net produce of 2 molecules of ATP and two of NADH. The two molecules of NADH themselves go on to produce approximately 3 molecules of ATP each, click on genes, proteins and metabolites below to link to respective articles
6. Coenzyme Q10 – Coenzyme Q10, also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ10 /ˌkoʊ ˌkjuː ˈtɛn/, CoQ, or Q10 is a coenzyme that is ubiquitous in the bodies of most animals. It is a 1, 4-benzoquinone, where Q refers to the chemical group and 10 refers to the number of isoprenyl chemical subunits in its tail. This fat-soluble substance, which resembles a vitamin, is present in most eukaryotic cells and it is a component of the electron transport chain and participates in aerobic cellular respiration, which generates energy in the form of ATP. Ninety-five percent of the bodys energy is generated this way. Therefore, those organs with the highest energy requirements—such as the heart, liver, there are three redox states of CoQ10, fully oxidized, semiquinone, and fully reduced. There are two factors that lead to deficiency of CoQ10 in humans, reduced biosynthesis, and increased use by the body. Biosynthesis is the source of CoQ10. Biosynthesis requires at least 12 genes, and mutations in many of them cause CoQ deficiency, CoQ10 levels also may be affected by other genetic defects. The role of statins in deficiencies is controversial, some chronic disease conditions also are thought to reduce the biosynthesis of and increase the demand for CoQ10 in the body, but there are no definite data to support these claims. Usually, toxicity is not observed with high doses of CoQ10, a daily dosage up to 3600 mg was found to be tolerated by healthy as well as unhealthy persons. Some adverse effects, however, largely gastrointestinal, are reported with high intakes. The observed safe level risk assessment method indicated that the evidence of safety is strong at intakes up to 1200 mg/day, although CoQ10 may be measured in blood plasma, these measurements reflect dietary intake rather than tissue status. Currently, most clinical centers measure CoQ10 levels in cultured skin fibroblasts, muscle biopsies, culture fibroblasts can be used also to evaluate the rate of endogenous CoQ10 biosynthesis, by measuring the uptake of 14C-labelled p-hydroxybenzoate. CoQ10 shares a biosynthetic pathway with cholesterol, the synthesis of an intermediary precursor of CoQ10, mevalonate, is inhibited by some beta blockers, blood pressure-lowering medication, and statins, a class of cholesterol-lowering drugs. Statins can reduce levels of CoQ10 by up to 40%. CoQ10 is not approved by the U. S. Food and it is sold as a dietary supplement. In the U. S. supplements are not regulated as drugs, how CoQ10 is manufactured is not regulated and different batches and brands may vary significantly. A2004 laboratory analysis by ConsumerLab. com of CoQ10 supplements on the found that some did not contain the quantity identified on the product label
7. Dihydrolipoamide dehydrogenase – Dihydrolipoamide dehydrogenase, also known as dihydrolipoyl dehydrogenase, mitochondrial, is an enzyme that in humans is encoded by the DLD gene. DLD is an enzyme that oxidizes dihydrolipoamide to lipoamide. Dihydrolipoamide dehydrogenase is an enzyme that plays a vital role in energy metabolism in eukaryotes. This enzyme is required for the reaction of at least five different multi-enzyme complexes. Additionally, DLD is a flavoenzyme oxidoreductase that contains a disulfide bridge. The enzyme associates into tightly bound homodimers required for its enzymatic activity, the protein encoded by the DLD gene comes together with another protein to form a dimer in the central metabolic pathway. Several amino acids within the catalytic pocket have been identified as important to DLD function, including R281, when bound the NAD+ molecule, required for catalysis, is not close to the FAD moiety. However, when NADH is bound instead, it is stacked directly op top of the FAD central structure. The current hE3 structures show directly that the disease-causing mutations occur at three locations in the enzyme, the dimer interface, the active site, and the FAD. In these complexes, DLD converts dihydrolipoic acid and NAD+ into lipoic acid, DLD also has diaphorase activity, being able to catalyze the oxidation of NADH to NAD+ by using different electron acceptors such as O2, labile ferric iron, nitric oxide, and ubiquinone. DLD is thought to have a pro-oxidant role by reducing oxygen to a superoxide or ferric to ferrous iron, diaphorase activity of DLD may have an antioxidant role through its ability to scavenge nitric oxide and to reduce ubiquinone to ubiquinol. The dihyrolipamide dehydrogenase gene is known to have multiple splice variants, certain DLD mutations can simultaneously induce the loss of a primary metabolic activity and the gain of a moonlighting proteolytic activity. The moonlighting proteolytic activity of DLD is revealed by conditions that destabilize the DLD homodimer, the moonlighting proteolytic activity of DLD could also arise under pathological conditions. With its proteolytic function, DLD removes a functionally vital domain from the N-terminus of frataxin, in humans, mutations in DLD are linked to a severe disorder of infancy with failure to thrive, hypotonia, and metabolic acidosis. With its proteolytic function, DLD causes a deficiency in frataxin and this protein may use the morpheein model of allosteric regulation
8. Dihydrolipoyl transacetylase – Dihydrolipoyl transacetylase is an enzyme component of the multienzyme pyruvate dehydrogenase complex. The pyruvate dehydrogenase complex is responsible for the decarboxylation step that links glycolysis to the citric acid cycle. This involves the transformation of pyruvate from glycolysis into acetyl-CoA which is used in the citric acid cycle to carry out cellular respiration. There are three different enzyme components in the pyruvate dehydrogenase complex, pyruvate dehydrogenase is responsible for the oxidation of pyruvate, dihydrolipoyl transacetylase transfers the acetyl group to coenzyme A, and dihydrolipoyl dehydrogenase regenerates the lipoamide. In humans, dihydrolipoyl transacetylase enzymatic activity resides in the pyruvate dehydrogenase complex component E2 that is encoded by the DLAT gene, the systematic name of this enzyme class is acetyl-CoA, enzyme N6-lysine S-acetyltransferase. Other names in use include, All dihydrolipoyl transacetylases have a unique multidomain structure consisting of,3 lipoyl domains, an interaction domain. Interestingly all the domains are connected by disordered, low complexity linker regions, depending on the species, multiple subunits of dihydrolipoyl transacetylase enzymes can arrange together into either a cubic or dodecahedral shape. The cubic core structure, found in such as Azotobacter vinelandii, is made up of 24 subunits total. The catalytic domains are assembled into trimers with the site located at the subunit interface. The topology of this active site is identical to that of chloramphenicol acetyltransferase. Eight of these trimers are then arranged into a truncated cube. The two main substrates, CoA and the lipoamide, are found at two opposite entrances of a 30 Å long channel which runs between the subunits and forms the catalytic center, CoA enters from the inside of the cube, and the lipoamide enters from the outside. The subunits are arranged in sets of three, similar to the trimers in the cubic shape, with each set making up one of the 20 dodecahedral vertices. Dihydrolipoyl transacetylase participates in the decarboxylation reaction that links glycolysis to the citric acid cycle. The various parts of cellular respiration take place in different parts of the cell, thus pyruvate dehydrogenase complexes are found in the mitochondria of eukaryotes. Pyruvate decarboxylation requires a few cofactors in addition to the enzymes that make up the complex, the first is thiamine pyrophosphate, which is used by pyruvate dehydrogenase to oxidize pyruvate and to form a hydroxyethyl-TPP intermediate. This intermediate is taken up by dihydrolipoyl transacetylase and reacted with a second lipoamide cofactor to generate an acetyl-dihydrolipoyl intermediate and this second intermediate can then be attacked by the nucleophilic sulfur attached to Coenzyme A, and the dihydrolipoamide is released. This results in the production of acetyl CoA, which is the end goal of pyruvate decarboxylation, the dihydrolipoamide is taken up by dihydrolipoyl dehydrogenase, and with the additional cofactors FAD and NAD+, regenerates the original lipoamide