Glycolysis
Overview
 
Glycolysis is the metabolic pathway
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...

 that converts glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 C6H12O6, into pyruvate, CH3COCOO + H+. The free energy
Thermodynamic free energy
The thermodynamic free energy is the amount of work that a thermodynamic system can perform. The concept is useful in the thermodynamics of chemical or thermal processes in engineering and science. The free energy is the internal energy of a system less the amount of energy that cannot be used to...

 released in this process is used to form the high-energy compounds ATP (adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

) and NADH (reduced nicotinamide adenine dinucleotide).

Glycolysis is a definite sequence of ten reactions involving ten intermediate compounds (one of the steps involves two intermediates).
Encyclopedia
Glycolysis is the metabolic pathway
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...

 that converts glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 C6H12O6, into pyruvate, CH3COCOO + H+. The free energy
Thermodynamic free energy
The thermodynamic free energy is the amount of work that a thermodynamic system can perform. The concept is useful in the thermodynamics of chemical or thermal processes in engineering and science. The free energy is the internal energy of a system less the amount of energy that cannot be used to...

 released in this process is used to form the high-energy compounds ATP (adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

) and NADH (reduced nicotinamide adenine dinucleotide).

Glycolysis is a definite sequence of ten reactions involving ten intermediate compounds (one of the steps involves two intermediates). The intermediates provide entry points to glycolysis. For example, most monosaccharides, such as fructose
Fructose
Fructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...

, glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

, and galactose
Galactose
Galactose , sometimes abbreviated Gal, is a type of sugar that is less sweet than glucose. It is a C-4 epimer of glucose....

, can be converted to one of these intermediates. The intermediates may also be directly useful. For example, the intermediate dihydroxyacetone phosphate (DHAP) is a source of the glycerol that combines with fatty acids to form fat.

It occurs, with variations, in nearly all organisms, both aerobic and anaerobic
Anaerobic respiration
Anaerobic respiration is a form of respiration using electron acceptors other than oxygen. Although oxygen is not used as the final electron acceptor, the process still uses a respiratory electron transport chain; it is respiration without oxygen...

. The wide occurrence of glycolysis indicates that it is one of the most ancient known metabolic pathways.

The most common type of glycolysis is the Embden-Meyerhof-Parnas pathway (EMP pathway), which was first discovered by Gustav Embden
Gustav Embden
Gustav Georg Embden was a German chemist who conducted studies on carbohydrate metabolism and muscle contraction, and was the first to discover and link together all the steps involved in the conversion of glycogen to lactic acid...

, Otto Meyerhof and Jakub Karol Parnas
Jakub Karol Parnas
Jakub Karol Parnas, also known as Yakov Oskarovich Parnas was a prominent Jewish-Polish–Soviet biochemist who contributed to the discovery of the Embden–Meyerhof–Parnas pathway, together with Otto Fritz Meyerhof and Gustav Georg Embden...

. Glycolysis also refers to other pathways, such as the Entner–Doudoroff pathway and various heterofermentative and homofermentative pathways. However, the discussion here will be limited to the Embden-Meyerhof pathway.

The entire glycolysis pathway can be separated into two phases:
  1. The Preparatory Phase - in which ATP is consumed and is hence also known as the investment phase
  2. The Pay Off Phase - in which ATP is produced.

Overview

The overall reaction of glycolysis is:
D-[Glucose] [Pyruvate]
+ 2 [NAD]+ + 2 [ADP] + 2 [P]i 2 + 2 [NADH] + 2 H+ + 2 [ATP] + 2 H2O
>
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:
  • each exists in the form of a hydrogen phosphate anion (HPO42-), dissociating to contribute 2 H+ overall
  • each liberates an oxygen atom when it binds to an ADP (adenosine diphosphate
    Adenosine diphosphate
    Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....

    ) molecule, contributing 2 O overall

Charges are balanced by the difference between ADP and ATP. In the cellular environment, all three hydroxy 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 hydroxy 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 anaerobic
Anaerobic respiration
Anaerobic respiration is a form of respiration using electron acceptors other than oxygen. Although oxygen is not used as the final electron acceptor, the process still uses a respiratory electron transport chain; it is respiration without oxygen...

 fermentations
Fermentation (biochemistry)
Fermentation is the process of extracting energy from the oxidation of organic compounds, such as carbohydrates, using an endogenous electron acceptor, which is usually an organic compound. In contrast, respiration is where electrons are donated to an exogenous electron acceptor, such as oxygen,...

, 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
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

 or lactic acid
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...

. 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. 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 substrate-level phosphorylation
Substrate-level phosphorylation
Substrate-level phosphorylation is a type of metabolism that results in the formation and creation of adenosine triphosphate or guanosine triphosphate by the direct transfer and donation of a phosphoryl group to adenosine diphosphate or guanosine diphosphate from a phosphorylated reactive...

 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.

Elucidation of the pathway

In 1860, Louis Pasteur
Louis Pasteur
Louis Pasteur was a French chemist and microbiologist born in Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of diseases. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies and anthrax. His experiments...

 discovered that microorganism
Microorganism
A microorganism or microbe is a microscopic organism that comprises either a single cell , cell clusters, or no cell at all...

s are responsible for fermentation
Fermentation (biochemistry)
Fermentation is the process of extracting energy from the oxidation of organic compounds, such as carbohydrates, using an endogenous electron acceptor, which is usually an organic compound. In contrast, respiration is where electrons are donated to an exogenous electron acceptor, such as oxygen,...

. In 1897, Eduard Buchner
Eduard Buchner
Eduard Buchner was a German chemist and zymologist, awarded with the 1907 Nobel Prize in Chemistry thanks to his work on fermentation.-Early years:...

 found that extracts of certain cells can cause fermentation. In 1905, Arthur Harden
Arthur Harden
Sir Arthur Harden FRS was an English biochemist. He shared the Nobel Prize in Chemistry in 1929 with Hans Karl August Simon von Euler-Chelpin for their investigations into the fermentation of sugar and fermentative enzymes....

 and William Young
William John Young
William John Young was an English biochemist.-Beginnings and Education:William John Young was born on 26 January 1878 in Withington, Manchester, England. He received a B.Sc. in 1898 and a M.Sc. in 1902 at Owen College, Manchester...

along with Nick Sheppard determined 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
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....

) are required together for fermentation to proceed. The details of the pathway were eventually determined by 1940, with a major input from Otto Meyerhof and some years later by Luis Leloir. 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.

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 (G3P
Glyceraldehyde 3-phosphate
Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GADP, GAP, TP, GALP or PGAL, is a chemical compound that occurs as an intermediate in several central metabolic pathways of all organisms...

).
The first step in glycolysis is phosphorylation of glucose by a family of enzymes called hexokinase
Hexokinase
A hexokinase is an enzyme that phosphorylates a six-carbon sugar, a hexose, to a hexose phosphate. In most tissues and organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate the most important product....

s to form glucose 6-phosphate (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 from the phosphorolysis
Phosphorolysis
Phosphorolysis is the cleavage of a compound in which inorganic phosphate is the attacking group. It is analogous to hydrolysis.An example of this is glycogen breakdown by glycogen phosphorylase, which catalyzes attack by inorganic phosphate on the terminal glycosyl residue at the nonreducing end...

 or hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

 of intracellular starch or glycogen.

In animal
Animal
Animals are a major group of multicellular, eukaryotic organisms of the kingdom Animalia or Metazoa. Their body plan eventually becomes fixed as they develop, although some undergo a process of metamorphosis later on in their life. Most animals are motile, meaning they can move spontaneously and...

s, an isozyme
Isozyme
Isozymes are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. These enzymes usually display different kinetic parameters Isozymes (also known as isoenzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. These enzymes...

 of hexokinase called glucokinase
Glucokinase
Glucokinase is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Glucokinase occurs in cells in the liver, pancreas, gut, and brain of humans and most other vertebrates...

 is also used in the liver, which has a much lower affinity for glucose (Km in the vicinity of normal glycemia
Glycemia
Glycemia means the presence, or the level, of glucose in one's blood. Related words include:* Hyperglycemia, an unusually high concentration of sugar in the blood* Hypoglycemia, an unusually low concentration of sugar in the blood...

), 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+


G6P is then rearranged into fructose 6-phosphate
Fructose 6-phosphate
Fructose 6-phosphate is fructose sugar phosphorylated on carbon 6 . The β-D-form of this compound is very common in cells. The vast majority of glucose and fructose entering a cell will become converted to this at some point...

 (F6P) by glucose phosphate isomerase. Fructose
Fructose
Fructose, or fruit sugar, is a simple monosaccharide found in many plants. It is one of the three dietary monosaccharides, along with glucose and galactose, that are absorbed directly into the bloodstream during digestion. Fructose was discovered by French chemist Augustin-Pierre Dubrunfaut in 1847...

 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. Under conditions of high F6P concentration, this reaction readily runs in reverse. This phenomenon can be explained through Le Chatelier's Principle
Le Châtelier's principle
In chemistry, Le Chatelier's principle, also called the Chatelier's principle, can be used to predict the effect of a change in conditions on a chemical equilibrium. The principle is named after Henry Louis Le Chatelier and sometimes Karl Ferdinand Braun who discovered it independently...

. Isomerization to a keto sugar is necessary for carbanion stabilization in the fourth reaction step (below).


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 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
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

. 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 pyrophosphate-dependent phosphofructokinase
PFP (enzyme)
Diphosphate—fructose-6-phosphate 1-phosphotransferase also known as PFP is an enzyme of carbohydrate metabolism in plants and some bacteria...

 (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:
Mg2+


Destabilizing the molecule in the previous reaction allows the hexose ring to be split by aldolase into two triose sugars, dihydroxyacetone phosphate, a ketone, and glyceraldehyde 3-phosphate
Glyceraldehyde 3-phosphate
Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GADP, GAP, TP, GALP or PGAL, is a chemical compound that occurs as an intermediate in several central metabolic pathways of all organisms...

, an aldehyde. 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.


Triosephosphate isomerase rapidly interconverts dihydroxyacetone phosphate with glyceraldehyde 3-phosphate
Glyceraldehyde 3-phosphate
Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GADP, GAP, TP, GALP or PGAL, is a chemical compound that occurs as an intermediate in several central metabolic pathways of all organisms...

 (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. 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.
The triose sugars are dehydrogenated and inorganic phosphate is added to them, forming 1,3-bisphosphoglycerate
1,3-Bisphosphoglycerate
1,3-Bisphosphoglyceric acid is a 3-carbon organic molecule present in most, if not all, living organisms. It primarily exists as a metabolic intermediate in both glycolysis during respiration and the Calvin cycle during photosynthesis...

.

The hydrogen is used to reduce two molecules of NAD+, a hydrogen carrier, to give NADH + H+ for each triose.

Hydrogen atom balance and charge balance are both maintained because the phosphate (Pi) group actually exists in the form of a hydrogen phosphate anion (HPO42-), which dissociates to contribute the extra H+ ion and gives a net charge of -3 on both sides.


This step is the enzymatic transfer of a phosphate group from 1,3-bisphosphoglycerate
1,3-Bisphosphoglycerate
1,3-Bisphosphoglyceric acid is a 3-carbon organic molecule present in most, if not all, living organisms. It primarily exists as a metabolic intermediate in both glycolysis during respiration and the Calvin cycle during photosynthesis...

 to ADP by phosphoglycerate kinase
Phosphoglycerate kinase
Phosphoglycerate kinase is a transferase enzyme used in the seventh step of glycolysis. It transfers a phosphate group from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-Phosphoglycerate....

, forming ATP and 3-phosphoglycerate. 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 substrate-level phosphorylation
Substrate-level phosphorylation
Substrate-level phosphorylation is a type of metabolism that results in the formation and creation of adenosine triphosphate or guanosine triphosphate by the direct transfer and donation of a phosphoryl group to adenosine diphosphate or guanosine diphosphate from a phosphorylated reactive...

 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 ATPMg2-, balancing the charges at -5 both sides.

Cofactors:
Mg2+


Phosphoglycerate mutase
Phosphoglycerate mutase
-Overview:Phosphoglycerate mutase is an enzyme that catalyzes step 8 of glycolysis. It catalyzes the internal transfer of a phosphate group from C-3 to C-2 which results in the conversion of 3-phosphoglycerate to 2-phosphoglycerate through a 2,3-bisphosphoglycerate intermediate.This enzyme is...

 now forms 2-phosphoglycerate
2-Phosphoglycerate
2-Phosphoglyceric acid , or 2-phosphoglycerate, is a glyceric acid which serves as the substrate in the ninth step of glycolysis. It is catalyzed by enolase into phosphoenolpyruvate , the penultimate step in the conversion of glucose to pyruvate.-In Glycolysis: -References:...

.


Enolase
Enolase
Enolase, also known as phosphopyruvate dehydratase, is a metalloenzyme responsible for the catalysis of the conversion of 2-phosphoglycerate to phosphoenolpyruvate , the ninth and penultimate step of glycolysis. Enolase belongs to the class Lyase. Enolase can also catalyze the reverse reaction,...

 next forms phosphoenolpyruvate
Phosphoenolpyruvate
Phosphoenolpyruvic acid , or phosphoenolpyruvate as the anion, is an important chemical compound in biochemistry. It has the high-energy phosphate bond found in living organisms, and is involved in glycolysis and gluconeogenesis...

 from 2-phosphoglycerate
2-Phosphoglycerate
2-Phosphoglyceric acid , or 2-phosphoglycerate, is a glyceric acid which serves as the substrate in the ninth step of glycolysis. It is catalyzed by enolase into phosphoenolpyruvate , the penultimate step in the conversion of glucose to pyruvate.-In Glycolysis: -References:...

.

Cofactors:
2 Mg2+: one "conformational" ion to coordinate with the carboxylate group of the substrate, and one "catalytic" ion that participates in the dehydration.


A final substrate-level phosphorylation
Substrate-level phosphorylation
Substrate-level phosphorylation is a type of metabolism that results in the formation and creation of adenosine triphosphate or guanosine triphosphate by the direct transfer and donation of a phosphoryl group to adenosine diphosphate or guanosine diphosphate from a phosphorylated reactive...

 now forms a molecule of pyruvate and a molecule of ATP by means of the enzyme pyruvate kinase
Pyruvate kinase
Pyruvate kinase is an enzyme involved in glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate to ADP, yielding one molecule of pyruvate and one molecule of ATP.-Reaction:The reaction with pyruvate kinase:...

. This serves as an additional regulatory step, similar to the phosphoglycerate kinase step.

Cofactors:
Mg2+

Regulation

Glycolysis is regulated by slowing down or speeding up certain steps in the glycolysis pathway. This is accomplished by inhibiting or activating the enzymes that are involved. The steps that are regulated may be determined by calculating the change in free energy, ΔG, for each step. If a step's products and reactants are in equilibrium, then the step is assumed to not be regulated. Since the change in free energy is zero for a system at equilibrium, any step with a free energy change near zero is not being regulated. If a step is being regulated, then that step's enzyme is not converting reactants into products as fast as it could, resulting in a build-up of reactants, which would be converted to products if the enzyme were operating faster. Since the reaction is thermodynamically favorable, the change in free energy for the step will be negative. A step with a large negative change in free energy is assumed to be regulated.

Free energy changes

Concentrations of metabolites in erythrocytes
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...

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 reaction quotient
Reaction quotient
In chemistry, a reaction quotient: Qr is a function of the activities or concentrations of the chemical species involved in a chemical reaction. In the special case that the reaction is at equilibrium the reaction quotient is equal to the equilibrium constant....

. This requires knowing the concentrations of the metabolites
Metabolomics
Metabolomics is the scientific study of chemical processes involving metabolites. Specifically, metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind", the study of their small-molecule metabolite profiles...

. All of these values are available for erythrocytes
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...

, with the exception of the concentrations of NAD+ and NADH. The ratio of NAD+ to NADH in the cytoplasm is approximately 1000 in the step 6, something that makes the oxidation of glyceraldehyde-3-phosphate more favourable.

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).
Change in free energy for each step of glycolysis
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 catalytically perfect
Kinetic perfection
Kinetic perfection, also known as catalytic perfection, refers to enzymes that are diffusion-limited; that is, the reaction they catalyze occurs as quickly as the reactants diffuse to the enzyme...

 enzyme; its rate is so fast that the reaction can be assumed to be in equilibrium. The fact that ΔG is not zero indicates that the actual concentrations in the erythrocyte are not accurately known.

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
Hexokinase
A hexokinase is an enzyme that phosphorylates a six-carbon sugar, a hexose, to a hexose phosphate. In most tissues and organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate the most important product....

 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
Glycogen
Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...

 or starch
Starch
Starch or amylum is a carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds. This polysaccharide is produced by all green plants as an energy store...

. 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
Phosphofructokinase
Phosphofructokinase-1 is the most important regulatory enzyme of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by many activators and inhibitors...

 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. On the converse, triglyceride
Triglyceride
A triglyceride is an ester derived from glycerol and three fatty acids. There are many triglycerides, depending on the oil source, some are highly unsaturated, some less so....

s 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.

Regulation

The three regulated enzymes are hexokinase
Hexokinase
A hexokinase is an enzyme that phosphorylates a six-carbon sugar, a hexose, to a hexose phosphate. In most tissues and organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate the most important product....

, phosphofructokinase, and pyruvate kinase
Pyruvate kinase
Pyruvate kinase is an enzyme involved in glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate to ADP, yielding one molecule of pyruvate and one molecule of ATP.-Reaction:The reaction with pyruvate kinase:...

.

The flux
Flux (biochemistry)
Flux, or metabolic flux is the rate of turnover of molecules through a metabolic pathway. Flux is regulated by the enzymes involved in a pathway. Within cells, regulation of flux is vital for all metabolic pathways to regulate the metabolic pathway's activity under different conditions...

 through the glycolytic pathway is adjusted in response to conditions both inside and outside the cell. The rate in liver is regulated to meet major cellular needs: (1) the production of ATP, (2) the provision of building blocks for biosynthetic reactions, and (3) to lower blood glucose, one of the major functions of the liver. When blood sugar falls, glycolysis is halted in the liver to allow the reverse process, gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

. In glycolysis, the reactions catalyzed by hexokinase, phosphofructokinase, and pyruvate kinase are effectively irreversible
Irreversible
Irreversible may refer to:*Irreversible process, in thermodynamics, a process that is not reversible*Irréversible, a 2002 film*Irréversible , soundtrack to the film Irréversible...

 in most organisms. In metabolic pathways, such enzymes are potential sites of control, and all three enzymes serve this purpose in glycolysis.

Hexokinase

In animals, regulation of blood glucose levels by the pancreas in conjunction with the liver is a vital part of homeostasis
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...

. In liver cells, extra G6P (glucose-6-phosphate) may be converted to G1P for conversion to glycogen
Glycogen
Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...

, or it is alternatively converted by glycolysis to acetyl-CoA
Acetyl-CoA
Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...

 and then citrate
Citrate
A citrate can refer either to the conjugate base of citric acid, , or to the esters of citric acid. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate.-Other citric acid ions:...

. Excess citrate
Citrate
A citrate can refer either to the conjugate base of citric acid, , or to the esters of citric acid. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate.-Other citric acid ions:...

 is exported to the cytosol, where ATP citrate lyase
ATP citrate lyase
ATP citrate lyase is an enzyme that represents an important step in fatty acid biosynthesis. This step in fatty acid biosynthesis occurs because ATP citrate lyase is the link between the metabolism of carbohydrates to the production of fatty acids.-Function:ATP citrate lyase is the primary enzyme...

 will regenerate acetyl-CoA
Acetyl-CoA
Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...

 and OAA. The acetyl-CoA
Acetyl-CoA
Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...

 is then used for fatty acid synthesis
Fatty acid synthesis
Fatty acid synthesis is the creation of fatty acids from acetyl-CoA and malonyl-CoA precursors through action of enzymes called fatty acid synthases...

 and cholesterol synthesis, two important ways of utilizing excess glucose when its concentration is high in blood. Liver contains both hexokinase
Hexokinase
A hexokinase is an enzyme that phosphorylates a six-carbon sugar, a hexose, to a hexose phosphate. In most tissues and organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate the most important product....

 and glucokinase
Glucokinase
Glucokinase is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Glucokinase occurs in cells in the liver, pancreas, gut, and brain of humans and most other vertebrates...

; the latter catalyses the phosphorylation of glucose to G6P and is not inhibited by G6P. Thus, it allows glucose to be converted into glycogen, fatty acids, and cholesterol even when hexokinase activity is low. This is important when blood glucose levels are high. During hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...

, the glycogen can be converted back to G6P and then converted to glucose by the liver-specific enzyme glucose 6-phosphatase
Glucose 6-phosphatase
Glucose 6-phosphatase is an enzyme that hydrolyzes glucose-6-phosphate resulting in the creation of a phosphate group and free glucose. Glucose is then exported from the cell via glucose transporter membrane proteins...

. This reverse reaction is an important role of liver cells to maintain blood sugars levels during fasting. This is critical for brain function, since the brain utilizes glucose as an energy source under most conditions.

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
Adenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...

 and fructose 2,6-bisphosphate
Fructose 2,6-bisphosphate
Fructose 2,6-bisphosphate abbreviated Fru-2,6-P2, is a metabolite that allosterically affects the activity of the enzymes phosphofructokinase 1 and fructose 1,6-bisphosphatase to regulate glycolysis and gluconeogenesis...

 (F2,6BP).

Fructose 2,6-bisphosphate
Fructose 2,6-bisphosphate
Fructose 2,6-bisphosphate abbreviated Fru-2,6-P2, is a metabolite that allosterically affects the activity of the enzymes phosphofructokinase 1 and fructose 1,6-bisphosphatase to regulate glycolysis and gluconeogenesis...

 (F2,6BP) is a very potent activator of phosphofructokinase (PFK-1), which is synthesised when F6P is phosphorylated by a second phosphofructokinase (PFK2
PFK2
Phosphofructokinase 2 or fructose biphosphatase 2 , is an enzyme responsible for regulating the rates of glycolysis and gluconeogenesis in the human body. It is a homodimer of 55 kDa subunits arranged in a head-to-head fashion, with each polypeptide chain consisting of independent kinase and...

). In liver, when blood sugar is low and glucagon
Glucagon
Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...

 elevates cAMP, PFK2
PFK2
Phosphofructokinase 2 or fructose biphosphatase 2 , is an enzyme responsible for regulating the rates of glycolysis and gluconeogenesis in the human body. It is a homodimer of 55 kDa subunits arranged in a head-to-head fashion, with each polypeptide chain consisting of independent kinase and...

 is phosphorylated by protein kinase A. The phosphorylation inactivates PFK2
PFK2
Phosphofructokinase 2 or fructose biphosphatase 2 , is an enzyme responsible for regulating the rates of glycolysis and gluconeogenesis in the human body. It is a homodimer of 55 kDa subunits arranged in a head-to-head fashion, with each polypeptide chain consisting of independent kinase and...

, and another domain on this protein becomes active as fructose 2,6-bisphosphatase, which converts F2,6BP back to F6P. Both glucagon
Glucagon
Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...

 and epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

 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 phosphofructokinase
Phosphofructokinase
Phosphofructokinase-1 is the most important regulatory enzyme of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by many activators and inhibitors...

 and an increase in activity of fructose 1,6-bisphosphatase, 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.

ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 competes with AMP
Adenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...

 for the allosteric effector site on the PFK enzyme. ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 concentrations in cells are much higher than those of AMP
Adenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...

, typically 100-fold higher, but the concentration of ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 does not change more than about 10% under physiological conditions, whereas a 10% drop in ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 results in a 6-fold increase in AMP
Adenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...

. Thus, the relevance of ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 as an allosteric effector is questionable. An increase in AMP
Adenosine monophosphate
Adenosine monophosphate , also known as 5'-adenylic acid, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid and the nucleoside adenosine. AMP consists of a phosphate group, the sugar ribose, and the nucleobase adenine...

 is a consequence of a decrease in energy charge
Energy charge
Energy charge is an index used to measure the energy status of biological cells. It is related to ATP and ADP concentrations and its value effects rates of metabolism.From Stryer:"Many reactions in metabolism are controlled by the energy status of the cell...

 in the cell.

Citrate
Citrate
A citrate can refer either to the conjugate base of citric acid, , or to the esters of citric acid. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate.-Other citric acid ions:...

 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 acetyl-CoA
Acetyl-CoA
Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...

 for fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...

 and cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

 synthesis.

Pyruvate kinase

This enzyme catalyzes the last step of glycolysis, in which pyruvate and ATP are formed. Regulation of this enzyme is discussed in the main topic, pyruvate kinase
Pyruvate kinase
Pyruvate kinase is an enzyme involved in glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate to ADP, yielding one molecule of pyruvate and one molecule of ATP.-Reaction:The reaction with pyruvate kinase:...

.

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+.

Fermentation

One method of doing this is to simply have the pyruvate do the oxidation; in this process, the pyruvate is converted to lactate
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...

 (the conjugate base of lactic acid) in a process called lactic acid fermentation
Lactic acid fermentation
Lactic acid fermentation is a biological process by which sugars such as glucose, fructose, and sucrose, are converted into cellular energy and the metabolic byproduct lactate. It is an anaerobic fermentation reaction that occurs in some bacteria and animal cells, such as muscle cells, in the...

:
pyruvate + NADH + H+ → lactate + NAD+


This process occurs in the bacteria involved in making yogurt (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, or in infarcted heart muscle cells. In many tissues, this is a cellular last resort for energy; most animal tissue cannot maintain anaerobic respiration for an extended length of time.

Some organisms, such as yeast, convert NADH back to NAD+ in a process called ethanol fermentation
Ethanol fermentation
Ethanol fermentation, also referred to as alcoholic fermentation, is a biological process in which sugars such as glucose, fructose, and sucrose are converted into cellular energy and thereby produce ethanol and carbon dioxide as metabolic waste products...

. In this process, the pyruvate is converted first to acetaldehyde and carbon dioxide, then to ethanol.

Lactic acid fermentation
Lactic acid fermentation
Lactic acid fermentation is a biological process by which sugars such as glucose, fructose, and sucrose, are converted into cellular energy and the metabolic byproduct lactate. It is an anaerobic fermentation reaction that occurs in some bacteria and animal cells, such as muscle cells, in the...

 and ethanol fermentation
Ethanol fermentation
Ethanol fermentation, also referred to as alcoholic fermentation, is a biological process in which sugars such as glucose, fructose, and sucrose are converted into cellular energy and thereby produce ethanol and carbon dioxide as metabolic waste products...

 can occur in the absence of oxygen. This anaerobic fermentation allows many single-cell organisms to use glycolysis as their only energy source.

Anaerobic respiration

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
Cellular respiration
Cellular respiration is the set of the metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products. The reactions involved in respiration are catabolic reactions that involve...

: 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 respiration

In aerobic organism
Aerobic organism
An aerobic organism or aerobe is an organism that can survive and grow in an oxygenated environment.Faculitative anaerobes grow and survive in an oxygenated environment and so do aerotolerant anaerobes.-Glucose:...

s, a complex mechanism has been developed to use the oxygen in air as the final electron acceptor of respiration.
  • First, pyruvate is converted to acetyl-CoA
    Acetyl-CoA
    Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...

     and CO2 within the mitochondria in a process called pyruvate decarboxylation.
  • Second, the acetyl-CoA enters the citric acid cycle
    Citric acid cycle
    The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...

    , also known as Krebs Cycle, where it is fully oxidized to carbon dioxide and water
    Water
    Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...

    , producing yet more NADH.
  • Third, the NADH is oxidized to NAD+ by the electron transport chain
    Electron transport chain
    An electron transport chain couples electron transfer between an electron donor and an electron acceptor with the transfer of H+ ions across a membrane. The resulting electrochemical proton gradient is used to generate chemical energy in the form of adenosine triphosphate...

    , using oxygen as the final electron acceptor. This process creates a "hydrogen ion gradient" across the inner membrane of the mitochondria.
  • Fourth, the proton gradient is used to produce a large amount of ATP in a process called oxidative phosphorylation
    Oxidative phosphorylation
    Oxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate . Although the many forms of life on earth use a range of different nutrients, almost all aerobic organisms carry out oxidative phosphorylation to produce ATP,...

    .

Intermediates for other pathways

This article concentrates on the catabolic 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 anabolic pathways, and, as a consequence, flux through the pathway is critical to maintain a supply of carbon skeletons for biosynthesis.

In addition, not all carbon entering the pathway leaves as pyruvate and may be extracted at earlier stages to provide carbon compounds for other pathways.

These metabolic pathways are all strongly reliant on glycolysis as a source of metabolites:
  • Gluconeogenesis
    Gluconeogenesis
    Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

  • Lipid metabolism
    Lipid metabolism
    Lipid metabolism refers to the processes that involve the intercourse and degradation of lipids.The types of lipids involved include:* Bile salts* Cholesterols* Eicosanoids* Glycolipids* Ketone bodies* Fatty acids - see also fatty acid metabolism...

  • Pentose phosphate pathway
    Pentose phosphate pathway
    The pentose phosphate pathway is a process that generates NADPH and pentoses . There are two distinct phases in the pathway. The first is the oxidative phase, in which NADPH is generated, and the second is the non-oxidative synthesis of 5-carbon sugars...

  • Citric acid cycle
    Citric acid cycle
    The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...

    , which in turn leads to:
  • Amino acid synthesis
    Amino acid synthesis
    For the non-biological synthesis of amino acids see: Strecker amino acid synthesisAmino acid synthesis is the set of biochemical processes by which the various amino acids are produced from other compounds. The substrates for these processes are various compounds in the organism's diet or growth...

  • Nucleotide synthesis
  • Tetrapyrrole synthesis


From an anabolic
Anabolism
Anabolism is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy. One way of categorizing metabolic processes, whether at the cellular, organ or organism level is as 'anabolic' or as 'catabolic', which is the opposite...

 metabolism perspective, the NADH has a role to drive synthetic reactions, doing so by directly or indirectly reducing the pool of NADP+ in the cell to NADPH, which is another important reducing agent for biosynthetic pathways in a cell.

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 Pyruvate kinase deficiency
Pyruvate kinase deficiency
Pyruvate kinase deficiency, also called erythrocyte pyruvate kinase deficiency, is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells and causes them to deform into echinocytes on peripheral blood smears.Both autosomal dominant and recessive...

, leading to chronic hemolytic anemia.

Cancer

Malignant rapidly-growing tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

 cells typically have glycolytic rates that are up to 200 times higher than those of their normal tissues of origin. This phenomenon was first described in 1930 by Otto Warburg and is referred to as the Warburg effect
Warburg effect
The phrase "Warburg effect" is used for two unrelated observations in biochemistry, one in plant physiology and the other in oncology, both due to Nobel laureate Otto Heinrich Warburg.-Plant physiology:...

. The Warburg hypothesis
Warburg hypothesis
The Warburg effect is the observation that cancer cells exhibit glycolysis with lactate secretion and mitochondrial respiration even in the presence of oxygen....

 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.

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 cancers by imaging
Chemical imaging
Chemical imaging is the analytical capability to create a visual image of components distribution from simultaneous measurement of spectra and spatial, time informations....

 uptake of 2-18F-2-deoxyglucose
Fluorodeoxyglucose
Fludeoxyglucose or fluorodeoxyglucose , commonly abbreviated 18F-FDG or FDG, is a radiopharmaceutical used in the medical imaging modality positron emission tomography...

 (FDG) (a radioactive modified hexokinase substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...

) with positron emission tomography
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...

 (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 ketogenic diet
Ketogenic diet
The ketogenic diet is a high-fat, adequate-protein, low-carbohydrate diet that in medicine is used primarily to treat difficult-to-control epilepsy in children. The diet mimics aspects of starvation by forcing the body to burn fats rather than carbohydrates...

.

Alzheimer's disease

Disfunctioning glycolysis or glucose metabolism in fronto-temporo-parietal and cingulate cortices has been associated with Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

, probably due to the decreased amyloid β (1-42) (Aβ42) and increased tau
Tau protein
Tau proteins are proteins that stabilize microtubules. They are abundant in neurons of the central nervous system and are less common elsewhere, but are also expressed at very low levels in CNS astrocytes and oligodendrocytes...

, phosphorylated tau in cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...

 (CSF)

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
Calvin cycle
The Calvin cycle or Calvin–Benson-Bassham cycle or reductive pentose phosphate cycle or C3 cycle or CBB cycle is a series of biochemical redox reactions that take place in the stroma of chloroplasts in photosynthetic organisms...

.
This article Alternative names Alternative nomenclature
1 glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

Glc dextrose
3 fructose 6-phosphate
Fructose 6-phosphate
Fructose 6-phosphate is fructose sugar phosphorylated on carbon 6 . The β-D-form of this compound is very common in cells. The vast majority of glucose and fructose entering a cell will become converted to this at some point...

F6P
4 fructose 1,6-bisphosphate
Fructose 1,6-bisphosphate
Fructose 1,6-bisphosphate is fructose sugar phosphorylated on carbons 1 and 6 . The β-D-form of this compound is very common in cells...

F1,6BP fructose 1,6-diphosphate FBP, FDP, F1,6DP
5 dihydroxyacetone phosphate DHAP glycerone phosphate
6 glyceraldehyde 3-phosphate
Glyceraldehyde 3-phosphate
Glyceraldehyde 3-phosphate, also known as triose phosphate or 3-phosphoglyceraldehyde and abbreviated as G3P, GADP, GAP, TP, GALP or PGAL, is a chemical compound that occurs as an intermediate in several central metabolic pathways of all organisms...

GADP 3-phosphoglyceraldehyde PGAL, G3P, GALP,GAP,TP
7 1,3-bisphosphoglycerate
1,3-Bisphosphoglycerate
1,3-Bisphosphoglyceric acid is a 3-carbon organic molecule present in most, if not all, living organisms. It primarily exists as a metabolic intermediate in both glycolysis during respiration and the Calvin cycle during photosynthesis...

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
2-Phosphoglycerate
2-Phosphoglyceric acid , or 2-phosphoglycerate, is a glyceric acid which serves as the substrate in the ninth step of glycolysis. It is catalyzed by enolase into phosphoenolpyruvate , the penultimate step in the conversion of glucose to pyruvate.-In Glycolysis: -References:...

2PG glycerate 2-phosphate
10 phosphoenolpyruvate
Phosphoenolpyruvate
Phosphoenolpyruvic acid , or phosphoenolpyruvate as the anion, is an important chemical compound in biochemistry. It has the high-energy phosphate bond found in living organisms, and is involved in glycolysis and gluconeogenesis...

PEP
11 pyruvate Pyr pyruvic acid

See also

  • carbohydrate catabolism
    Carbohydrate catabolism
    Carbohydrate catabolism is the breakdown of carbohydrates into smaller units. Carbohydrates literally undergo combustion to retrieve the large amounts of energy in their bonds...

  • Citric acid cycle
    Citric acid cycle
    The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...

  • Cori cycle
    Cori cycle
    The Cori cycle , named after its discoverers, Carl Cori and Gerty Cori, refers to the metabolic pathway in which lactate produced by anaerobic glycolysis in the muscles moves to the liver and is converted to glucose, which then returns to the muscles and is converted back to lactate.-Cycle:Muscular...

  • Fermentation (biochemistry)
    Fermentation (biochemistry)
    Fermentation is the process of extracting energy from the oxidation of organic compounds, such as carbohydrates, using an endogenous electron acceptor, which is usually an organic compound. In contrast, respiration is where electrons are donated to an exogenous electron acceptor, such as oxygen,...

  • Gluconeogenesis
    Gluconeogenesis
    Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

  • Pentose phosphate pathway
    Pentose phosphate pathway
    The pentose phosphate pathway is a process that generates NADPH and pentoses . There are two distinct phases in the pathway. The first is the oxidative phase, in which NADPH is generated, and the second is the non-oxidative synthesis of 5-carbon sugars...

  • Pyruvate decarboxylation
  • Triose kinase
    Triose kinase
    Triose kinase is an enzyme in the liver that takes part in an alternate glycolytic pathway. It phosphorylates a three-carbon sugar to allow it to continue along the standard glycolytic pathway....



External links

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
x
OK