Summary of aerobic respiration Glycolysis (from glycose, an older term for glucose + -lysis degradation) is the that converts C 6H 12O 6, into, CH 3COCOO − + H +. The released in this process is used to form the high-energy molecules ATP () and NADH (). Glycolysis is a determined sequence of ten -catalyzed reactions.

Biochemistry and Nutrition. Cori cycle: contents in brief. What is the Cori cycle? Where does the Cori cycle occur?

The intermediates provide entry points to glycolysis. For example, most monosaccharides, such as and, can be converted to one of these intermediates. The intermediates may also be directly useful. For example, the intermediate (DHAP) is a source of the glycerol that combines with fatty acids to form fat. Glycolysis is an oxygen independent metabolic pathway, meaning that it does not use molecular oxygen (i.e. Atmospheric oxygen) for any of its reactions. However the products of glycolysis ( and + H +) are sometimes using atmospheric oxygen.

When molecular oxygen is used for the metabolism of the products of glycolysis the process is usually referred to as, whereas if no oxygen is used the process is said to be. Thus, glycolysis occurs, with variations, in nearly all organisms, both and. The wide occurrence of glycolysis indicates that it is one of the most ancient metabolic pathways. Indeed, the reactions that constitute glycolysis and its parallel pathway, the, occur metal-catalyzed under the of the oceans, also in the absence of enzymes. Glycolysis could thus have originated from chemical constraints of the prebiotic world. Glycolysis occurs in most organisms in the of the cell. The most common type of glycolysis is the Embden–Meyerhof–Parnas (EMP pathway), which was discovered by,, and.

Glycolysis also refers to other pathways, such as the and various heterofermentative and homofermentative pathways. However, the discussion here will be limited to the Embden–Meyerhof–Parnas pathway. The entire glycolysis pathway can be separated into two phases: • The Preparatory/Investment Phase – wherein ATP is consumed • The Pay Off Phase – wherein ATP is produced. + 2 [NADH] + 2 H + + 2 [ATP] + 2 H 2O The use of symbols in this equation makes it appear unbalanced with respect to oxygen atoms, hydrogen atoms, and charges.

Atom balance is maintained by the two phosphate (P i) groups: • Each exists in the form of a anion (HPO 4 2−), dissociating to contribute 2 H + overall • Each liberates an oxygen atom when it binds to an ADP () molecule, contributing 2 O overall Charges are balanced by the difference between ADP and ATP. In the cellular environment, all three hydroxyl groups of ADP dissociate into −O − and H +, giving ADP 3−, and this ion tends to exist in an ionic bond with Mg 2+, giving ADPMg −.

ATP behaves identically except that it has four hydroxyl groups, giving ATPMg 2−. When these differences along with the true charges on the two phosphate groups are considered together, the net charges of −4 on each side are balanced. For simple, 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. Many bacteria use inorganic compounds as hydrogen acceptors to regenerate the NAD +. Cells performing synthesize much more ATP, but not as part of glycolysis. These further aerobic reactions use and NADH + H + from glycolysis. Eukaryotic aerobic respiration produces approximately 34 additional molecules of ATP for each glucose molecule, however most of these are produced by a vastly different mechanism to the in glycolysis. The lower-energy production, per glucose, of anaerobic respiration relative to aerobic respiration, results in greater flux through the pathway under hypoxic (low-oxygen) conditions, unless alternative sources of anaerobically oxidizable substrates, such as fatty acids, are found. Metabolism of common, including glycolysis,, and.

History [ ] The pathway of glycolysis as it is known today took almost 100 years to fully discover. The combined results of many smaller experiments were required in order to understand the pathway as a whole. The first steps in understanding glycolysis began in the nineteenth century with the wine industry.

For economic reasons, the French wine industry sought to investigate why wine sometime turned distasteful, instead of fermenting into alcohol. French scientist researched this issue during the 1850s, and the results of his experiments began the long road to elucidating the pathway of glycolysis.

His experiments showed that fermentation occurs by the action of living; and that yeast's glucose consumption decreased under aerobic conditions of fermentation, in comparison to anaerobic conditions (the ). Eduard Buchner. Discovered cell-free fermentation. While Pasteur's experiments were groundbreaking, insight into the component steps of glycolysis were provided by the non-cellular fermentation experiments of during the 1890s.

Buchner demonstrated that the conversion of glucose to ethanol was possible using a non-living extract of yeast (due to the action of in the extract). This experiment not only revolutionized biochemistry, but also allowed later scientists to analyze this pathway in a more controlled lab setting. In a series of experiments (1905-1911), scientists and discovered more pieces of glycolysis.. They discovered the regulatory effects of ATP on glucose consumption during alcohol fermentation. They also shed light on the role of one compound as a glycolysis intermediate: fructose 1,6-bisphosphate. The elucidation of fructose 1,6-diphosphate was accomplished by measuring CO 2 levels when yeast juice was incubated with glucose.

CO 2 production increased rapidly then slowed down. Harden and Young noted that this process would restart if an inorganic phosphate (Pi) was added to the mixture. Harden and Young deduced that this process produced organic phosphate esters, and further experiments allowed them to extract fructose diphosphate (F-1,6-DP).

And along with Nick Sheppard determined, in a second experiment, that a heat-sensitive high-molecular-weight subcellular fraction (the enzymes) and a heat-insensitive low-molecular-weight cytoplasm fraction (ADP, ATP and NAD + and other ) are required together for fermentation to proceed. This experiment begun by observing that dialyzed (purified) yeast juice could not ferment or even create a sugar phosphate. This mixture was rescued with the addition of undialyzed yeast extract that had been boiled.

Boiling the yeast extract renders all proteins inactive (as it denatures them). The ability of boiled extract plus dialyzed juice to complete fermentation suggests that the cofactors were non-protein in character. Otto Meyerhof.

One of the main scientists involved in completing the puzzle of glycolysis In the 1920s was able to link together some of the many individual pieces of glycolysis discovered by Buchner, Harden, and Young. Meyerhof and his team was able to extract different glycolytic enzymes from, and combine them to artificially create the pathway from glycogen to lactic acid. Simple Minds Sparkle In The Rain Rar Files.

In one paper, Meyerhof and scientist Renate Junowicz-Kockolaty investigated the reaction that splits fructose 1,6-diphosohate into the two triose phosphates. Previous work proposed that the split occurred via 1,3-diphosphoglyceraldehye plus an oxidizing enzyme and cozymase. Meyerhoff and Junowicz found that the equilibrium constant for the isomerase and aldoses reaction were not affected by inorganic phosphates or any other cozymase or oxidizing enzymes. They further removed diphosphoglyceraldehyde as a possible intermediate in glycolysis.

With all of these pieces available by the 1930s, proposed a detailed, step-by-step outline of that pathway we now know as glycolysis. The biggest difficulties in determining the intricacies of the pathway were due to the very short lifetime and low steady-state concentrations of the intermediates of the fast glycolytic reactions. By the 1940s, Meyerhof, Embden and many other biochemists had finally completed the puzzle of glycolysis.

The understanding of the isolated pathway has been expanded in the subsequent decades, to include further details of its regulation and integration with other metabolic pathways. 2 × Preparatory phase [ ] The first five steps are regarded as the preparatory (or investment) phase, since they consume energy to convert the glucose into two three-carbon sugar phosphates (). D- ( Glc) ( HK) a α- D- ( G6P) H + + The first step in glycolysis is phosphorylation of glucose by a family of enzymes called to form (G6P). This reaction consumes ATP, but it acts to keep the glucose concentration low, promoting continuous transport of glucose into the cell through the plasma membrane transporters. In addition, it blocks the glucose from leaking out – the cell lacks transporters for G6P, and free diffusion out of the cell is prevented due to the charged nature of G6P. Glucose may alternatively be formed from the or of intracellular starch or glycogen.

In, an of hexokinase called is also used in the liver, which has a much lower affinity for glucose (K m in the vicinity of normal glycemia), and differs in regulatory properties. The different substrate affinity and alternate regulation of this enzyme are a reflection of the role of the liver in maintaining blood sugar levels.

Cofactors: Mg 2+. Α- D- ( G6P) ( PGI) an β- D- ( F6P) G6P is then rearranged into (F6P). Can also enter the glycolytic pathway by phosphorylation at this point.

The change in structure is an isomerization, in which the G6P has been converted to F6P. The reaction requires an enzyme, phosphohexose isomerase, to proceed. This reaction is freely reversible under normal cell conditions. However, it is often driven forward because of a low concentration of F6P, which is constantly consumed during the next step of glycolysis. Sim 2 Clean Pack Installer.

Under conditions of high F6P concentration, this reaction readily runs in reverse. This phenomenon can be explained through. Isomerization to a keto sugar is necessary for carbanion stabilization in the fourth reaction step (below).

Β- D- ( F6P) ( PFK-1) a β- D- ( F1,6BP) ATP H + + ADP The energy expenditure of another ATP in this step is justified in 2 ways: The glycolytic process (up to this step) is now irreversible, and the energy supplied destabilizes the molecule. Because the reaction catalyzed by (PFK-1) is coupled to the hydrolysis of ATP (an energetically favorable step) it is, in essence, irreversible, and a different pathway must be used to do the reverse conversion during. This makes the reaction a key regulatory point (see below). This is also the rate-limiting step. Furthermore, the second phosphorylation event is necessary to allow the formation of two charged groups (rather than only one) in the subsequent step of glycolysis, ensuring the prevention of free diffusion of substrates out of the cell. The same reaction can also be catalyzed by ( PFP or PPi-PFK), which is found in most plants, some bacteria, archea, and protists, but not in animals.

This enzyme uses pyrophosphate (PPi) as a phosphate donor instead of ATP. It is a reversible reaction, increasing the flexibility of glycolytic metabolism. A rarer ADP-dependent PFK enzyme variant has been identified in archaean species. Cofactors: Mg 2+. Β- D- ( F1,6BP) ( ALDO) a D- ( GADP) ( DHAP) + Destabilizing the molecule in the previous reaction allows the hexose ring to be split by into two triose sugars: (a ketose), and (an aldose).

There are two classes of aldolases: class I aldolases, present in animals and plants, and class II aldolases, present in fungi and bacteria; the two classes use different mechanisms in cleaving the ketose ring. Electrons delocalized in the carbon-carbon bond cleavage associate with the alcohol group. The resulting carbanion is stabilized by the structure of the carbanion itself via resonance charge distribution and by the presence of a charged ion prosthetic group. Pay-off phase [ ] The second half of glycolysis is known as the pay-off phase, characterised by a net gain of the energy-rich molecules ATP and NADH. Since glucose leads to two triose sugars in the preparatory phase, each reaction in the pay-off phase occurs twice per glucose molecule. This yields 2 NADH molecules and 4 ATP molecules, leading to a net gain of 2 NADH molecules and 2 ATP molecules from the glycolytic pathway per glucose. ( GADP) ( GAPDH) an D- ( 1,3BPG) NAD + + P i NADH + H + The aldehyde groups of the triose sugars are, and is added to them, forming.

The hydrogen is used to reduce two molecules of, a hydrogen carrier, to give NADH + H + for each triose. Hydrogen atom balance and charge balance are both maintained because the phosphate (P i) group actually exists in the form of a anion (HPO 4 2−), which dissociates to contribute the extra H + ion and gives a net charge of -3 on both sides. Here, (AsO 4 3−), an anion akin to inorganic phosphate may replace phosphate as a substrate to form 1-arseno-3-phoshoglycerate.

This, however, is unstable and readily hydrolyzes to form, the intermediate in the next step of the pathway. As a consequence of bypassing this step, the molecule of ATP generated from in the next reaction will not be made, even though the reaction proceeds. As a result, arsenate is an uncoupler of glycolysis. ( 1,3BPG) ( PGK) a ( 3PG) ADP ATP ( PGK) This step is the enzymatic transfer of a phosphate group from to ADP by, forming ATP and.

At this step, glycolysis has reached the break-even point: 2 molecules of ATP were consumed, and 2 new molecules have now been synthesized. This step, one of the two steps, requires ADP; thus, when the cell has plenty of ATP (and little ADP), this reaction does not occur. Because ATP decays relatively quickly when it is not metabolized, this is an important regulatory point in the glycolytic pathway. ADP actually exists as ADPMg −, and ATP as ATPMg 2−, balancing the charges at -5 both sides.

Cofactors: Mg 2+. Structure of anaerobic glycolysis components showed using Fischer projections, left, and polygonal model, right. The compounds correspond to glucose (GLU), glucose 6-phosphate (G6P), fructose 6-phosphate (F6P), fructose 1,6-bisphosphate ( F16BP), dihydroxyacetone phosphate (DHAP), glyceraldehyde 3-phosphate(GA3P), 1,3-bisphosphoglycerate (13BPG), 3-phosphoglycerate (3PG), 2-phosphoglycerate (2PG), phosphoenolpyruvate (PEP), pyruvate (PIR), and lactate (LAC). The enzymes which participate of this pathway are indicated by underlined numbers, and correspond to hexokinase ( 1), glucose-6-phosphate isomerase ( 2), phosphofructokinase-1 ( 3), fructose-bisphosphate aldolase ( 4), triosephosphate isomerase ( 5), glyceraldehyde-3-phosphate dehydrogenase ( 5), phosphoglycerate kinase ( 7), phosphoglycerate mutase ( 8), phosphopyruvate hydratase (enolase) ( 9), pyruvate kinase ( 10), and lactate dehydrogenase ( 11).

The participant coenzymes (NAD +, NADH + H +, ATP and ADP), inorganic phosphate, H 2O and CO 2 were omitted in these representations. The phosphorylation reactions from ATP, as well the ADP phosphorylation reactions in later steps of glycolysis are shown as ~P respectively entering or going out the pathway.

The oxireduction reactions using NAD + or NADH are observed as hydrogens “2H” going out or entering the pathway. Biochemical logic [ ] The existence of more than one point of regulation indicates that intermediates between those points enter and leave the glycolysis pathway by other processes. For example, in the first regulated step, converts glucose into glucose-6-phosphate. Instead of continuing through the glycolysis pathway, this intermediate can be converted into glucose storage molecules, such as. The reverse reaction, breaking down, e.g., glycogen, produces mainly glucose-6-phosphate; very little free glucose is formed in the reaction. The glucose-6-phosphate so produced can enter glycolysis after the first control point.

In the second regulated step (the third step of glycolysis), converts fructose-6-phosphate into fructose-1,6-bisphosphate, which then is converted into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. The dihydroxyacetone phosphate can be removed from glycolysis by conversion into glycerol-3-phosphate, which can be used to form triglycerides. Conversely, can be broken down into fatty acids and glycerol; the latter, in turn, can be into dihydroxyacetone phosphate, which can enter glycolysis after the second control point.

Regulation of the rate limiting enzymes [ ] The four are,,, and. The through the glycolytic pathway is adjusted in response to conditions both inside and outside the cell. The internal factors that regulate glycolysis do so primarily to provide in adequate quantities for the cell’s needs. The external factors act primarily on the,, and, which can remove large quantities of glucose from the blood after meals (thus preventing by storing the excess glucose as fat or glycogen, depending on the tissue type). The liver is also capable of releasing glucose into the blood between meals, during fasting, and exercise thus preventing by means of and.

These latter reactions coincide with the halting of glycolysis in the liver. In animals, regulation of blood glucose levels by the pancreas in conjunction with the liver is a vital part of. The in the are sensitive to the blood glucose concentration. A rise in the blood glucose concentration causes them to release into the blood, which has an effect particularly on the liver, but also on and cells, causing these tissues to remove glucose from the blood. When the blood sugar falls the pancreatic beta cells cease insulin production, but, instead, stimulate the neighboring pancreatic to release into the blood. This, in turn, causes the liver to release glucose into the blood by breaking down stored, and by means of. If the fall in the blood glucose level is particularly rapid or severe, other glucose sensors cause the release of from the into the blood.

This has the same action as glucagon on glucose metabolism, but its effect is more pronounced. In the liver glucagon and epinephrine cause the of the key, rate limiting enzymes of glycolysis,,,, and. Insulin has the opposite effect on these enzymes. The phosphorylation and dephosphorylation of these enzymes (ultimately in response to the glucose level in the blood) is the dominant manner by which these pathways are controlled in the liver, fat, and muscle cells. Thus the phosphorylation of inhibits glycolysis, whereas its dephosphorylation through the action of insulin stimulates glycolysis.

In addition and act independently of the hormonal effects as controls at the entry points of glucose into the cells of different tissues. Hexokinase responds to the (G6P) level in the cell, or, in the case of, to the blood sugar level in the blood to impart entirely intracellular controls of the glycolytic pathway in different tissues (see ). When glucose has been converted into G6P by hexokinase or glucokinase, it can either be converted to (G1P) for conversion to, or it is alternatively converted by glycolysis to, which enters the where it is converted into and then into.

Excess is exported from the mitochondrion back into to the cytosol, where regenerates and (OAA). The is then used for and, two important ways of utilizing excess glucose when its concentration is high in blood. The rate limiting enzymes catalyzing these reactions perform these functions when they have been dephosphorylated through the action of insulin on the liver cells. Between meals, during, or, glucagon and epinephrine are released into the blood. This causes liver glycogen to be converted back to G6P, and then converted to glucose by the liver-specific enzyme and released into the blood.

Glucagon and epinephrine also stimulate gluconeogenesis, which coverts non-carbohydrate substrates into G6P, which joins the G6P derived from glycogen, or substitutes for it when the liver glycogen store have been depleted. This is critical for brain function, since the brain utilizes glucose as an energy source under most conditions. The simultaneously phosphorylation of, particularly,, but also, to a certain extent, prevents glycolysis occurring at the same time as gluconeogenesis and glycogenolysis. Hexokinase and glucokinase [ ].

B (: ​) All cells contain the enzyme, which catalyzes the conversion of glucose that has entered the cell into (G6P). Since the cell membrane is impervious to G6P, hexokinase essentially acts to transport glucose into the cells from which it can then no longer escape. Hexokinase is inhibited by high levels of G6P in the cell.

Thus the rate of entry of glucose into cells partially depends on how fast G6P can be disposed of by glycolysis, and by (in the cells which store glycogen, namely liver and muscles)., unlike, is not inhibited by G6P. It occurs in liver cells, and will only phosphorylate the glucose entering the cell to form (G6P), when the sugar in the blood is abundant. This being the first step in the glycolytic pathway in the liver, it therefore imparts an additional layer of control of the glycolytic pathway in this organ.

Phosphofructokinase [ ]. (: ​) is an important control point in the glycolytic pathway, since it is one of the irreversible steps and has key allosteric effectors, and (F2,6BP). (F2,6BP) is a very potent activator of phosphofructokinase (PFK-1) that is synthesized when F6P is phosphorylated by a second phosphofructokinase (). In the liver, when blood sugar is low and elevates cAMP, is phosphorylated. The phosphorylation inactivates, and another domain on this protein becomes active as, which converts F2,6BP back to F6P. Both and cause high levels of cAMP in the liver.

The result of lower levels of liver fructose-2,6-bisphosphate is a decrease in activity of and an increase in activity of, so that gluconeogenesis (in essence, 'glycolysis in reverse') is favored. This is consistent with the role of the liver in such situations, since the response of the liver to these hormones is to release glucose to the blood. Competes with for the allosteric effector site on the PFK enzyme. Concentrations in cells are much higher than those of, typically 100-fold higher, but the concentration of does not change more than about 10% under physiological conditions, whereas a 10% drop in results in a 6-fold increase in. Thus, the relevance of as an allosteric effector is questionable.

An increase in is a consequence of a decrease in in the cell. Inhibits phosphofructokinase when tested in vitro by enhancing the inhibitory effect of ATP. However, it is doubtful that this is a meaningful effect in vivo, because citrate in the cytosol is utilized mainly for conversion to for and synthesis. Pyruvate kinase [ ]. Main article: Pyruvate kinase enzyme the last step of glycolysis, in which pyruvate and ATP are formed. Pyruvate kinase catalyzes the transfer of a from (PEP) to, yielding one molecule of and one molecule of.

Liver pyruvate kinase is indirectly regulated by and, through. This protein kinase phosphorylates liver pyruvate kinase to deactivate it. Muscle pyruvate kinase is not inhibited by epinephrine activation of protein kinase A. Glucagon signals fasting (no glucose available). Thus, glycolysis is inhibited in the liver but unaffected in muscle when fasting. An increase in blood sugar leads to secretion of, which activates phosphoprotein phosphatase I, leading to dephosphorylation and activation of pyruvate kinase. These controls prevent pyruvate kinase from being active at the same time as the enzymes that catalyze the reverse reaction ( and ), preventing a.

Post-glycolysis processes [ ] The overall process of glycolysis is: Glucose + 2 NAD + + 2 ADP + 2 P i → 2 Pyruvate + 2 NADH + 2 H + + 2 ATP + 2 H 2O If glycolysis were to continue indefinitely, all of the NAD + would be used up, and glycolysis would stop. To allow glycolysis to continue, organisms must be able to oxidize NADH back to NAD +. How this is performed depends on which external electron acceptor is available. Anoxic regeneration of NAD + [ ] One method of doing this is to simply have the pyruvate do the oxidation; in this process, pyruvate is converted to (the of lactic acid) in a process called: Pyruvate + NADH + H + → Lactate + NAD + This process occurs in the involved in making (the lactic acid causes the milk to curdle).

This process also occurs in animals under hypoxic (or partially anaerobic) conditions, found, for example, in overworked muscles that are starved of oxygen. In many tissues, this is a cellular last resort for energy; most animal tissue cannot tolerate anaerobic conditions for an extended period of time. Some organisms, such as yeast, convert NADH back to NAD + in a process called. In this process, the pyruvate is converted first to acetaldehyde and carbon dioxide, and then to ethanol. And can occur in the absence of oxygen. This anaerobic fermentation allows many single-cell organisms to use glycolysis as their only energy source.

Anoxic regeneration of NAD + is only an effective means of energy production during short, intense exercise in vertebrates, for a period ranging from 10 seconds to 2 minutes during a maximal effort in humans. (At lower exercise intensities it can sustain muscle activity in, such as seals, whales and other aquatic vertebrates, for very much longer periods of time.) Under these conditions NAD + is replenished by NADH donating its electrons to pyruvate to form lactate.

This produces 2 ATP molecules per glucose molecule, or about 5% of glucose's energy potential (38 ATP molecules in bacteria). But the speed at which ATP is produced in this manner is about 100 times that of oxidative phosphorylation. The pH in the cytoplasm quickly drops when hydrogen ions accumulate in the muscle, eventually inhibiting the enzymes involved in glycolysis. The burning sensation in muscles during hard exercise can be attributed to the release of hydrogen ions during the shift to glucose fermentation from glucose oxidation to carbon dioxide and water, when aerobic metabolism can no longer keep pace with the energy demands of the muscles. These hydrogen ions form a part of lactic acid. The body falls back on this less efficient but faster method of producing ATP under low oxygen conditions. This is thought to have been the primary means of energy production in earlier organisms before oxygen reached high concentrations in the atmosphere between 2000 and 2500 million years ago (see diagram above right), and thus would represent a more ancient form of energy production than the aerobic replenishment of NAD + in cells.

The liver in mammals gets rid of this excess lactate by transforming it back into pyruvate under aerobic conditions; see. Fermention of pyruvate to lactate is sometimes also called 'anaerobic glycolysis', however, glycolysis ends with the production of pyruvate regardless of the presence or absence of oxygen. In the above two examples of fermentation, NADH is oxidized by transferring two electrons to pyruvate.

However, anaerobic bacteria use a wide variety of compounds as the terminal electron acceptors in: nitrogenous compounds, such as nitrates and nitrites; sulfur compounds, such as sulfates, sulfites, sulfur dioxide, and elemental sulfur; carbon dioxide; iron compounds; manganese compounds; cobalt compounds; and uranium compounds. Aerobic regeneration of NAD +, and disposal of pyruvate [ ] In, a complex mechanism has been developed to use the oxygen in air as the final electron acceptor. • Firstly, the generated by glycolysis has to be transferred to the mitochondrion to be oxidized, and thus to regenerate the NAD + necessary for glycolysis to continue.

However the inner mitochondrial membrane is impermeable to NADH and NAD +. Use is therefore made of two “shuttles” to transport the electrons from NADH across the mitochondrial membrane. They are the and the. In the former the electrons from NADH are transferred to cytosolic to form. The malate then traverses the inner mitochondrial membrane into the mitochondrial matrix, where it is reoxidized by NAD + forming intra-mitochondrial oxaloacetate and NADH.

The oxaloacetate is then re-cycled to the cytosol via its conversion to aspartate which is readily transported out of the mitochondrion. In the glycerol phosphate shuttle electrons from cytosolic NADH are transferred to to form which readily traverses the outer mitochondrial membrane. Glycerol-3-phosphate is then reoxidized to dihydroxyacetone, donating its electrons to instead of NAD +. This reaction takes place on the inner mitochondrial membrane, allowing FADH 2 to donate its electrons directly to coenzyme Q () which is part of the which ultimately transfers electrons to molecular oxygen (O 2), with the formation of water, and the release of energy eventually captured in the form of. • The glycolytic end-product, pyruvate (plus NAD +) is converted to, CO 2 and NADH + H + within the in a process called. • The resulting acetyl-CoA enters the (or Krebs Cycle), where the acetyl group of the acetyl-CoA is converted into carbon dioxide by two decarboxylation reactions with the formation of yet more intra-mitochondrial NADH + H +. • The intra-mitochondrial NADH + H + is oxidized to NAD + by the, using oxygen as the final electron acceptor to form water.

The energy released during this process is used to create a hydrogen ion (or proton) gradient across the inner membrane of the mitochondrion. • Finally, the proton gradient is used to produce about 2.5 for every NADH + H + oxidized in a process called. Conversion of carbohydrates into fatty acids and cholesterol [ ] The pyruvate produced by glycolysis is an important intermediary in the conversion of carbohydrates into and.

This occurs via the conversion of pyruvate into in the. However, this acetyl CoA needs to be transported into cytosol where the synthesis of fatty acids and cholesterol occurs.

This cannot occur directly. To obtain cytosolic acetyl-CoA, (produced by the condensation of acetyl CoA with ) is removed from the and carried across the inner mitochondrial membrane into the.

There it is cleaved by into acetyl-CoA and oxaloacetate. The oxaloacetate is returned to mitochondrion as malate (and then back into oxaloacetate to transfer more acetyl-CoA out of the mitochondrion). The cytosolic acetyl-CoA can be carboxylated by into, the first committed step in the, or it can be combined with to form 3-hydroxy-3-methylglutaryl-CoA () which is the rate limiting step controlling the. Cholesterol can be used as is, as a structural component of cellular membranes, or it can be used to synthesize the,, and. Conversion of pyruvate into oxaloacetate for the citric acid cycle [ ] Pyruvate molecules produced by glycolysis are across the inner membrane, and into the matrix where they can either be and combined with to form CO 2, acetyl-CoA, and NADH, or they can be (by ) to form. This latter reaction 'fills up' the amount of oxaloacetate in the citric acid cycle, and is therefore an (from the Greek meaning to 'fill up'), increasing the cycle’s capacity to metabolize acetyl-CoA when the tissue's energy needs (e.g. In and ) are suddenly increased by activity.

In the all the intermediates (e.g. Citrate, iso-citrate, alpha-ketoglutarate, succinate, fumarate, malate and oxaloacetate) are regenerated during each turn of the cycle. Adding more of any of these intermediates to the mitochondrion therefore means that that additional amount is retained within the cycle, increasing all the other intermediates as one is converted into the other. Hence the addition of oxaloacetate greatly increases the amounts of all the citric acid intermediates, thereby increasing the cycle's capacity to metabolize acetyl CoA, converting its acetate component into CO 2 and water, with the release of enough energy to form 11 and 1 molecule for each additional molecule of acetyl CoA that combines with oxaloacetate in the cycle. To cataplerotically remove oxaloacetate from the citric cycle, can be transported from the mitochondrion into the cytoplasm, decreasing the amount of oxaloacetate that can be regenerated.

Furthermore, citric acid intermediates are. Intermediates for other pathways [ ] This article concentrates on the role of glycolysis with regard to converting potential chemical energy to usable chemical energy during the oxidation of glucose to pyruvate. Many of the metabolites in the glycolytic pathway are also used by pathways, and, as a consequence, flux through the pathway is critical to maintain a supply of carbon skeletons for biosynthesis. The following metabolic pathways are all strongly reliant on glycolysis as a source of metabolites: and many more. •, which begins with the dehydrogenation of, the first intermediate to be produced by glycolysis, produces various pentose sugars, and for the synthesis of and. • also starts with glucose-6-phosphate at the beginning of the glycolytic pathway.

•, for the formation of and, is produced from the glycolytic intermediate. • Various post-glycolytic pathways: • • • The which in turn leads to: • • • Although and glycolysis share many intermediates the one is not functionally a branch or tributary of the other. There are two regulatory steps in both pathways which, when active in the one pathway, are automatically inactive in the other. The two processes can therefore not be simultaneously active. Indeed, if both sets of reactions were highly active at the same time the net result would be the hydrolysis of four high energy phosphate bonds (two ATP and two GTP) per reaction cycle. Is the oxidizing agent in glycolysis, as it is in most other energy yielding metabolic reactions (e.g.

Of fatty acids, and during the ). The NADH thus produced is primarily used to ultimately transfer electrons to O 2 to produce water, or, when O 2 is not available, to produced compounds such as or (see Anoxic regeneration of NAD + above). NADH is rarely used for synthetic processes, the notable exception being. During and the reducing agent is. This difference exemplifies a general principle that NADPH is consumed during biosynthetic reactions, whereas NADH is generated in energy-yielding reactions.

The source of the NADPH is two-fold. When is oxidatively decarboxylated by “NADP +-linked malic enzyme', CO 2 and NADPH are formed. NADPH is also formed by the which converts glucose into ribose, which can be used in synthesis of and, or it can be catabolized to pyruvate. Glycolysis in disease [ ] Genetic diseases [ ] Glycolytic mutations are generally rare due to importance of the metabolic pathway, this means that the majority of occurring mutations result in an inability for the cell to respire, and therefore cause the death of the cell at an early stage.

However, some mutations are seen with one notable example being, leading to chronic hemolytic anemia. Cancer [ ] Malignant Tumor cells perform glycolysis at a rate that is ten times faster than their noncancerous tissue counterparts. During their genesis, limited capillary support often results in hypoxia (decreased O2 supply) within the tumor cells. Thus, these cells rely on anaerobic metabolic processes such as glycolysis for ATP. Some tumor cells overexpress specific glycolytic enzymes which results in higher rates of glycolysis.

Often these enzymes are Isoenzymes, of traditional glycolysis enzymes, that vary in their susceptibility to traditional feedback inhibition. The increase in glycolytic activity ultimately counteracts the effects of hypoxia by generating sufficient ATP from this anaerobic pathway. This phenomenon was first described in 1930 by and is referred to as the. The claims that cancer is primarily caused by dysfunctionality in mitochondrial metabolism, rather than because of uncontrolled growth of cells. A number of theories have been advanced to explain the Warburg effect. One such theory suggests that the increased glycolysis is a normal protective process of the body and that malignant change could be primarily caused by energy metabolism. This high glycolysis rate has important medical applications, as high aerobic glycolysis by malignant tumors is utilized clinically to diagnose and monitor treatment responses of by uptake of (FDG) (a modified hexokinase ) with (PET).

There is ongoing research to affect mitochondrial metabolism and treat cancer by reducing glycolysis and thus starving cancerous cells in various new ways, including a. Interactive pathway map [ ] Click on genes, proteins and metabolites below to link to respective articles. • The interactive pathway map can be edited at WikiPathways:. Alternative nomenclature [ ] Some of the metabolites in glycolysis have alternative names and nomenclature. In part, this is because some of them are common to other pathways, such as the. This article Alternative names Alternative nomenclature 1 Glc Dextrose 2 G6P 3 F6P 4 F1,6BP Fructose 1,6-diphosphate FBP, FDP, F1,6DP 5 DHAP Glycerone phosphate 6 GADP 3-Phosphoglyceraldehyde PGAL, G3P, GALP, GAP, TP 7 1,3BPG Glycerate-1,3-bisphosphate, glycerate-1,3-diphosphate, 1,3-diphosphoglycerate PGAP, BPG, DPG 8 3PG Glycerate-3-phosphate PGA, GP 9 2PG Glycerate-2-phosphate 10 PEP 11 Pyr Pyruvic acid See also [ ].