Glycolysis
Glycolysis is the
The wide occurrence of glycolysis in other species indicates that it is an ancient metabolic pathway.
The most common type of glycolysis is the Embden–Meyerhof–Parnas (EMP) pathway, which was discovered by
The glycolysis pathway can be separated into two phases:[5]
- Investment phase – wherein ATP is consumed
- Yield phase – wherein more ATP is produced than originally consumed
Overview
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. Atom balance is maintained by the two phosphate (Pi) groups:[6]
- Each exists in the form of a hydrogen phosphate anion ([HPO4]2−), dissociating to contribute 2H+ overall
- Each liberates an oxygen atom when it binds to an adenosine diphosphate (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 ADP3−, and this ion tends to exist in an ionic bond with Mg2+, giving ADPMg−. ATP behaves identically except that it has four hydroxyl groups, giving ATPMg2−. 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
Cells performing
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 monosaccharides, including glycolysis, gluconeogenesis, glycogenesis and glycogenolysis |
---|
History
The pathway of glycolysis as it is known today took almost 100 years to fully elucidate.[7] The combined results of many smaller experiments were required in order to understand the intricacies of the entire pathway.
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 sometimes turned distasteful, instead of fermenting into alcohol. French scientist Louis Pasteur researched this issue during the 1850s, and the results of his experiments began the long road to elucidating the pathway of glycolysis.[8] His experiments showed that fermentation occurs by the action of living microorganisms, yeasts, and that yeast's glucose consumption decreased under aerobic conditions of fermentation, in comparison to anaerobic conditions (the Pasteur effect).[9]
Insight into the component steps of glycolysis were provided by the non-cellular fermentation experiments of Eduard Buchner during the 1890s.[10][11] Buchner demonstrated that the conversion of glucose to ethanol was possible using a non-living extract of yeast, due to the action of enzymes in the extract.[12]: 135–148 This experiment not only revolutionized biochemistry, but also allowed later scientists to analyze this pathway in a more controlled laboratory setting. In a series of experiments (1905-1911), scientists Arthur Harden and William Young discovered more pieces of glycolysis.[13] 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.[12]: 151–158
The elucidation of fructose 1,6-bisphosphate was accomplished by measuring CO2 levels when yeast juice was incubated with glucose. CO2 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).
Arthur Harden and William Young 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 cofactors) 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.[13]
In the 1920s
In one paper, Meyerhof and scientist Renate Junowicz-Kockolaty investigated the reaction that splits fructose 1,6-diphosphate into the two triose phosphates. Previous work proposed that the split occurred via 1,3-diphosphoglyceraldehyde 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.[15]
With all of these pieces available by the 1930s, Gustav Embden proposed a detailed, step-by-step outline of that pathway we now know as glycolysis.[16] 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.[15] 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.
Sequence of reactions
Summary of reactions
+
dehydrogenase
2 × Pyruvate
Preparatory phase
The first five steps of Glycolysis are regarded as the preparatory (or investment) phase, since they consume energy to convert the glucose into two three-carbon sugar phosphates[5] (G3P).
d-Glucose (Glc) | Hexokinase glucokinase (HK) a transferase |
α-d- Glucose-6-phosphate (G6P)
| |
ATP | H+ + ADP | ||
Once glucose enters the cell, the first step is phosphorylation of glucose by a family of enzymes called hexokinases to form glucose 6-phosphate (G6P). This reaction consumes ATP, but it acts to keep the glucose concentration inside the cell low, promoting continuous transport of blood glucose into the cell through the plasma membrane transporters. In addition, phosphorylation 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 phosphorolysis or hydrolysis of intracellular starch or glycogen.
In animals, an isozyme of hexokinase called glucokinase is also used in the liver, which has a much lower affinity for glucose (Km 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: Mg2+
α-d-Glucose 6-phosphate (G6P) | Phosphoglucoisomerase (PGI)
an isomerase |
β-d-Fructose 6-phosphate (F6P) | |
G6P is then rearranged into
The change in structure is an isomerization, in which the G6P has been converted to F6P. The reaction requires an enzyme, phosphoglucose 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. Under conditions of high F6P concentration, this reaction readily runs in reverse. This phenomenon can be explained through
β-d-Fructose 6-phosphate (F6P) | Phosphofructokinase (PFK-1) a transferase |
β-d-Fructose 1,6-bisphosphate (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) becomes irreversible, and the energy supplied destabilizes the molecule. Because the reaction catalyzed by phosphofructokinase 1 (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 gluconeogenesis. This makes the reaction a key regulatory point (see below).
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 pyrophosphate-dependent phosphofructokinase (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.[17] A rarer ADP-dependent PFK enzyme variant has been identified in archaean species.[18]
Cofactors: Mg2+
β-d-Fructose 1,6-bisphosphate (F1,6BP) | Fructose-bisphosphate aldolase (ALDO) a lyase |
d-Glyceraldehyde 3-phosphate (GADP) | Dihydroxyacetone phosphate (DHAP) | ||
+ | |||||
Destabilizing the molecule in the previous reaction allows the hexose ring to be split by aldolase into two triose sugars: dihydroxyacetone phosphate (a ketose), and glyceraldehyde 3-phosphate (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.
Dihydroxyacetone phosphate (DHAP) | Triosephosphate isomerase (TPI) an isomerase |
d-Glyceraldehyde 3-phosphate (GADP) | |
Triosephosphate isomerase rapidly interconverts dihydroxyacetone phosphate with glyceraldehyde 3-phosphate (GADP) that proceeds further into glycolysis. This is advantageous, as it directs dihydroxyacetone phosphate down the same pathway as glyceraldehyde 3-phosphate, simplifying regulation.
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.[5] 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.
Glyceraldehyde 3-phosphate (GADP) | Glyceraldehyde phosphate dehydrogenase (GAPDH)
an oxidoreductase |
d- 1,3-Bisphosphoglycerate (1,3BPG)
| |
NAD+ + Pi | NADH + H+ | ||
The aldehyde groups of the triose sugars are
The hydrogen is used to reduce two molecules of
Hydrogen atom balance and charge balance are both maintained because the phosphate (Pi) group actually exists in the form of a hydrogen phosphate anion (HPO2−4),[6] which dissociates to contribute the extra H+ ion and gives a net charge of -3 on both sides.
Here,
1,3-Bisphosphoglycerate (1,3BPG)
|
Phosphoglycerate kinase (PGK) a transferase |
3-Phosphoglycerate (3PG)
| |
ADP | ATP | ||
Phosphoglycerate kinase (PGK) |
This step is the enzymatic transfer of a phosphate group from
ADP actually exists as ADPMg−, and ATP as ATPMg2−, balancing the charges at −5 both sides.
Cofactors: Mg2+
3-Phosphoglycerate (3PG)
|
Phosphoglycerate mutase (PGM) a mutase |
2-Phosphoglycerate (2PG)
| |
Cofactors: 2 Mg2+, one "conformational" ion to coordinate with the carboxylate group of the substrate, and one "catalytic" ion that participates in the dehydration.
Phosphoenolpyruvate (PEP)
|
Pyruvate kinase (PK) a transferase |
Pyruvate (Pyr)
| |
ADP + H+ | ATP | ||
A final
Cofactors: Mg2+
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, hexokinase converts glucose into glucose-6-phosphate. Instead of continuing through the glycolysis pathway, this intermediate can be converted into glucose storage molecules, such as glycogen or starch. 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), phosphofructokinase 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.[20] Conversely, triglycerides can be broken down into fatty acids and glycerol; the latter, in turn, can be converted into dihydroxyacetone phosphate, which can enter glycolysis after the second control point.
Free energy changes
Compound | Concentration / mM |
---|---|
Glucose | 5.0 |
Glucose-6-phosphate | 0.083 |
Fructose-6-phosphate | 0.014 |
Fructose-1,6-bisphosphate | 0.031 |
Dihydroxyacetone phosphate | 0.14 |
Glyceraldehyde-3-phosphate | 0.019 |
1,3-Bisphosphoglycerate | 0.001 |
2,3-Bisphosphoglycerate | 4.0 |
3-Phosphoglycerate | 0.12 |
2-Phosphoglycerate | 0.03 |
Phosphoenolpyruvate | 0.023 |
Pyruvate | 0.051 |
ATP | 1.85 |
ADP | 0.14 |
Pi | 1.0 |
The change in free energy, ΔG, for each step in the glycolysis pathway can be calculated using ΔG = ΔG°′ + RTln Q, where Q is the
Using the measured concentrations of each step, and the standard free energy changes, the actual free energy change can be calculated. (Neglecting this is very common - the delta G of ATP hydrolysis in cells is not the standard free energy change of ATP hydrolysis quoted in textbooks).
Step | Reaction | ΔG°′ (kJ/mol) |
ΔG (kJ/mol) |
---|---|---|---|
1 | Glucose + ATP4− → Glucose-6-phosphate2− + ADP3− + H+ | −16.7 | −34 |
2 | Glucose-6-phosphate2− → Fructose-6-phosphate2− | 1.67 | −2.9 |
3 | Fructose-6-phosphate2− + ATP4− → Fructose-1,6-bisphosphate4− + ADP3− + H+ | −14.2 | −19 |
4 | Fructose-1,6-bisphosphate4− → Dihydroxyacetone phosphate2− + Glyceraldehyde-3-phosphate2− | 23.9 | −0.23 |
5 | Dihydroxyacetone phosphate2− → Glyceraldehyde-3-phosphate2− | 7.56 | 2.4 |
6 | Glyceraldehyde-3-phosphate2− + Pi2− + NAD+ → 1,3-Bisphosphoglycerate4− + NADH + H+ | 6.30 | −1.29 |
7 | 1,3-Bisphosphoglycerate4− + ADP3− → 3-Phosphoglycerate3− + ATP4− | −18.9 | 0.09 |
8 | 3-Phosphoglycerate3− → 2-Phosphoglycerate3− | 4.4 | 0.83 |
9 | 2-Phosphoglycerate3− → Phosphoenolpyruvate3− + H2O | 1.8 | 1.1 |
10 | Phosphoenolpyruvate3− + ADP3− + H+ → Pyruvate− + ATP4− | −31.7 | −23.0 |
From measuring the physiological concentrations of metabolites in an erythrocyte it seems that about seven of the steps in glycolysis are in equilibrium for that cell type. Three of the steps — the ones with large negative free energy changes — are not in equilibrium and are referred to as irreversible; such steps are often subject to regulation.
Step 5 in the figure is shown behind the other steps, because that step is a side-reaction that can decrease or increase the concentration of the intermediate glyceraldehyde-3-phosphate. That compound is converted to dihydroxyacetone phosphate by the enzyme triose phosphate isomerase, which is a
Regulation
The enzymes that catalyse glycolysis are regulated via a range of biological mechanisms in order to control overall
- Gene Expression: Firstly, the cellular concentrations of glycolytic enzymes are modulated via transcription factors,[25] with several glycolysis enzymes themselves acting as regulatory protein kinases in the nucleus.[26]
- Allosteric inhibition and activation by Protein-protein interactions (PPI).[28] Indeed, some proteins interact with and regulate multiple glycolytic enzymes.[29]
- Post-translational modification (PTM).[30] In particular, phosphorylation and dephosphorylation is a key mechanism of regulation of pyruvate kinase in the liver.
- Localization[27]
Regulation by insulin in animals
In animals, regulation of blood glucose levels by the pancreas in conjunction with the liver is a vital part of
Regulated Enzymes in Glycolysis
The three
In addition hexokinase and
When glucose has been converted into G6P by hexokinase or glucokinase, it can either be converted to
Hexokinase and glucokinase
All cells contain the enzyme
Phosphofructokinase
Phosphofructokinase is an important control point in the glycolytic pathway, since it is one of the irreversible steps and has key allosteric effectors, AMP and fructose 2,6-bisphosphate (F2,6BP).
ATP competes with AMP for the allosteric effector site on the PFK enzyme. ATP concentrations in cells are much higher than those of AMP, typically 100-fold higher,[35] but the concentration of ATP does not change more than about 10% under physiological conditions, whereas a 10% drop in ATP results in a 6-fold increase in AMP.[36] Thus, the relevance of ATP as an allosteric effector is questionable. An increase in AMP is a consequence of a decrease in energy charge in the cell.
TIGAR, a p53 induced enzyme, is responsible for the regulation of phosphofructokinase and acts to protect against oxidative stress.[37] TIGAR is a single enzyme with dual function that regulates F2,6BP. It can behave as a phosphatase (fructuose-2,6-bisphosphatase) which cleaves the phosphate at carbon-2 producing F6P. It can also behave as a kinase (PFK2) adding a phosphate onto carbon-2 of F6P which produces F2,6BP. In humans, the TIGAR protein is encoded by C12orf5 gene. The TIGAR enzyme will hinder the forward progression of glycolysis, by creating a build up of fructose-6-phosphate (F6P) which is isomerized into glucose-6-phosphate (G6P). The accumulation of G6P will shunt carbons into the pentose phosphate pathway.[38][39]
Pyruvate kinase
The final step of glycolysis is catalysed by pyruvate kinase to form pyruvate and another ATP. It is regulated by a range of different transcriptional, covalent and non-covalent regulation mechanisms, which can vary widely in different tissues.[40][41][42] For example, in the liver, pyruvate kinase is regulated based on glucose availability. During fasting (no glucose available), glucagon activates protein kinase A which phosphorylates pyruvate kinase to inhibit it.[43] An increase in blood sugar leads to secretion of insulin, which activates protein phosphatase 1, leading to dephosphorylation and re-activation of pyruvate kinase.[43] These controls prevent pyruvate kinase from being active at the same time as the enzymes that catalyze the reverse reaction (pyruvate carboxylase and phosphoenolpyruvate carboxykinase), preventing a futile cycle.[43] Conversely, the isoform of pyruvate kinasein found in muscle is not affected by protein kinase A (which is activated by adrenaline in that tissue), so that glycolysis remains active in muscles even during fasting.[43]
Post-glycolysis processes
The overall process of glycolysis is:
- Glucose + 2 NAD+ + 2 ADP + 2 Pi → 2 Pyruvate + 2 NADH + 2 H+ + 2 ATP + 2 H2O
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
- Pyruvate + NADH + H+ → Lactate + NAD+
This process occurs in the
Some organisms, such as yeast, convert NADH back to NAD+ in a process called ethanol fermentation. In this process, the pyruvate is converted first to acetaldehyde and carbon dioxide, and then to ethanol.
Lactic acid fermentation and ethanol fermentation 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
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, 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 Cori cycle.
Fermentation 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 cellular respiration: 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 further catabolism of pyruvate
In
- Firstly, the ubiquinone) which is part of the electron transport chain which ultimately transfers electrons to molecular oxygen O2, with the formation of water, and the release of energy eventually captured in the form of ATP.
- The glycolytic end-product, pyruvate (plus NAD+) is converted to mitochondria in a process called pyruvate decarboxylation.
- The resulting acetyl-CoA enters the citric acid cycle (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 electron transport chain, 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 ATP for every NADH + H+ oxidized in a process called oxidative phosphorylation.[44]
Conversion of carbohydrates into fatty acids and cholesterol
The pyruvate produced by glycolysis is an important intermediary in the conversion of carbohydrates into
Conversion of pyruvate into oxaloacetate for the citric acid cycle
Pyruvate molecules produced by glycolysis are
To cataplerotically remove oxaloacetate from the citric cycle,
Intermediates for other pathways
This article concentrates on the
The following metabolic pathways are all strongly reliant on glycolysis as a source of metabolites: and many more.
- glucose-6-phosphate, the first intermediate to be produced by glycolysis, produces various pentose sugars, and NADPH for the synthesis of fatty acids and cholesterol.
- Glycogen synthesis also starts with glucose-6-phosphate at the beginning of the glycolytic pathway.
- glyceraldehyde-3-phosphate.
- Various post-glycolytic pathways:
- Fatty acid synthesis
- Cholesterol synthesis
- The citric acid cycle which in turn leads to:
Although gluconeogenesis 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.[49] 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.[49]
Glycolysis in disease
Diabetes
Cellular uptake of glucose occurs in response to insulin signals, and glucose is subsequently broken down through glycolysis, lowering blood sugar levels. However, the low insulin levels seen in diabetes result in hyperglycemia, where glucose levels in the blood rise and glucose is not properly taken up by cells. Hepatocytes further contribute to this hyperglycemia through gluconeogenesis. Glycolysis in hepatocytes controls hepatic glucose production, and when glucose is overproduced by the liver without having a means of being broken down by the body, hyperglycemia results.[50]
Genetic diseases
Glycolytic mutations are generally rare due to importance of the metabolic pathway; the majority of occurring mutations result in an inability of the cell to respire, and therefore cause the death of the cell at an early stage. However, some mutations (glycogen storage diseases and other inborn errors of carbohydrate metabolism) are seen with one notable example being pyruvate kinase deficiency, leading to chronic hemolytic anemia.[citation needed]
Cancer
Malignant tumor cells perform glycolysis at a rate that is ten times faster than their noncancerous tissue counterparts.[51] 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 (adenosine triphosphate). Some tumor cells overexpress specific glycolytic enzymes which result in higher rates of glycolysis.[52] 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.[53] This phenomenon was first described in 1930 by Otto Warburg and is referred to as the Warburg effect. The Warburg hypothesis claims that cancer is primarily caused by dysfunctionality in mitochondrial metabolism, rather than because of the 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.[54]
This high glycolysis rate has important medical applications, as high
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 ketogenic diet.[57][58][59]
Interactive pathway map
The diagram below shows human protein names. Names in other organisms may be different and the number of isozymes (such as HK1, HK2, ...) is likely to be different too.
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
- ^ The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".
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 Calvin cycle.
This article | Alternative | |||
---|---|---|---|---|
1 | Glucose | Glc | Dextrose | |
2 | Glucose-6-phosphate
|
G6P | ||
3 | Fructose-6-phosphate
|
F6P | ||
4 | Fructose-1,6-bisphosphate
|
F1,6BP | Fructose 1,6-diphosphate | FBP; FDP; F1,6DP |
5 | Dihydroxyacetone phosphate | DHAP | Glycerone phosphate | |
6 | Glyceraldehyde-3-phosphate
|
GADP | 3-Phosphoglyceraldehyde | PGAL; G3P; GALP; GAP; TP |
7 | 1,3-Bisphosphoglycerate
|
1,3BPG | Glycerate-1,3-bisphosphate, glycerate-1,3-diphosphate, 1,3-diphosphoglycerate |
PGAP; BPG; DPG |
8 | 3-Phosphoglycerate
|
3PG | Glycerate-3-phosphate | PGA; GP |
9 | 2-Phosphoglycerate
|
2PG | Glycerate-2-phosphate | |
10 | Phosphoenolpyruvate
|
PEP | ||
11 | Pyruvate
|
Pyr | Pyruvic acid conjugate base |
Structure of glycolysis components in Fischer projections and polygonal model
The intermediates of glycolysis depicted in Fischer projections show the chemical changing step by step. Such image can be compared to polygonal model representation.[60] Another comparation of Fischer projections and Poligonal Model in glycolysis is shown in a video.[61] Video animations in the same channel in YouTube can be seen for another metabolic pathway (Krebs Cycle) and the representation and applying of Polygonal Model in Organic Chemistry [62]
See also
- Carbohydrate catabolism
- Citric acid cycle
- Cori cycle
- Fermentation (biochemistry)
- Gluconeogenesis
- Glycolytic oscillation
- Glycogenoses (glycogen storage diseases)
- Inborn errors of carbohydrate metabolism
- Pentose phosphate pathway
- Pyruvate decarboxylation
- Triose kinase
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- ^ Bonafe C (23 September 2019). "Introduction to Polygonal Model - PART 1. Glycolysis and Structure of the Participant Molecules". YouTube. Archived from the original on 2021-11-04.
- ^ "Metabolism Animation and Polygonal Model". YouTube. Retrieved 2019-12-11.
External links
- A Detailed Glycolysis Animation provided by IUBMB (Adobe FlashRequired)
- The Glycolytic enzymes in Glycolysis at RCSB PDB
- Glycolytic cycle with animations at wdv.com
- Metabolism, Cellular Respiration and Photosynthesis - The Virtual Library of Biochemistry, Molecular Biology and Cell Biology
- The chemical logic behind glycolysis at ufp.pt
- Expasy biochemical pathways poster at ExPASy
- MedicalMnemonics.com: 317 5468
- metpath: Interactive representation of glycolysis