The main physiological function of carbohydrates is to provide energy for life activities.Sugar catabolism is the main way for organisms to obtain energy.There are three main pathways for the oxidative decomposition of sugars in organisms: anaerobic oxidation of sugars, aerobic oxidation of sugars, and pentose phosphate pathway.
Glycolysis refers to the process in which glucose is decomposed into pyruvate in the cytoplasm under anaerobic conditions, during which each molecule of glucose is decomposed to produce two molecules of pyruvate and two molecules of ATP, belonging to a type of sugar metabolism.There are ten steps of reaction, including three key enzymes (rate limiting enzymes): hexokinase, 6-phosphofructose kinase, pyruvate kinase.
In 2019, research found that tumor cells will have metabolic changes different from normal cells, and tumor cells themselves can adapt to changes in the metabolic environment through conversion between glycolysis and oxidative phosphorylation (OXPHOS).[1]
Chinese name
Glycolysis
Foreign name
glycolysis
biochemistry
Anaerobic respiration glucose
stage
Activation stageandEnergy release stage
atlas
Science popularization in China
Committed to authoritative science communication
The certification expert of this term is
Zhang Jingbo|researcher
Institute of Basic Medicine, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical Collegeto examine
In the absence of oxygen, the way for organisms to obtain energy from the degradation and metabolism of sugar is also a way for most organisms to prepare for the aerobic oxidation of glucose.In this process, six carbon glucose molecule splits into two molecules of three carbon pyruvate through more than ten steps of enzymatic reaction, and at the same time, two molecules of adenosine diphosphate (ADP) and inorganic phosphate (Pi) combine to form two moleculesAdenosine triphosphate(ATP)。
The further metabolism of pyruvate has different paths due to different species and oxygen supply.For example, in the absence of oxygen, pyruvate is reduced to lactic acid in the muscle cells of animals with strong contractionmicroorganismIt can be decomposed into ethanol or acetic acid;In the presence of oxygen, it is oxidized to carbon dioxide and water.
Reaction process
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The glycolysis process starts from the decomposition of glucose to pyruvate, and there are 10 enzyme catalyzed reactions in the whole process.
1. Glucose phosphorylation
The first step of glycolysis is the phosphorylation of glucose C6 catalyzed by hexokinase to form glucose 6-phosphate.The kinase requires Mg2+ion as a cofactor and consumes a molecule of ATP at the same time. This reaction is irreversible.
Isomerization of 2.6 glucose phosphate to fructose 6-phosphate
This is an aldose ketose isomerization reaction. The isomerization of aldose and ketose is catalyzed by hexose phosphate isomerase, which requires the participation of Mg2+ions. This reaction is reversible.
3.6-Fructose phosphate phosphorylates to fructose 1,6-diphosphate
This reaction is the phosphorylation of fructose 6-phosphate to fructose 1,6-diphosphate catalyzed by phosphofructose kinase, which consumes the second ATP molecule.
4.1, 6-fructose diphosphate cleavage
Under the action of aldolase, the bond between hexose phosphate fructose 1,6-diphosphate C3 and C4 is broken to produce a molecule of glyceraldehyde 3-phosphate and a molecule of dihydroxyacetone phosphate.
Interconversion of 5.3 glyceraldehyde phosphate and dihydroxyacetone phosphate
Glyceraldehyde 3-phosphate is the substrate of the next step of fermentation, so dihydroxyacetone phosphate needs to be converted into glyceraldehyde 3-phosphate under the catalysis of triose phosphate isomerase to further fermentation.
6.3 Oxidation of glyceraldehyde phosphate
Glyceraldehyde 3-phosphate is catalyzed by glyceraldehyde 3-phosphate dehydrogenase to produce 1,3-diphosphoglycerate in the presence of NAD+and H3P04, which is the only oxidation reaction in fermentation.
7.1, 3-diphosphoglycerate to 3-phosphoglycerate
Under the action of phosphoglycerate kinase, 1,3-diphosphoglycerate high-energy phosphoryl group is transferred to ADP to form ATP and 3-phosphoglycerate.
8. Glycerol-3-phosphoric acid is converted into glycerol-2-phosphoric acid
Under the catalysis of phosphoglycerate mutase, the phosphate group of C3 in glycerate 3-phosphate molecule is transferred to C2 to form glycerate 2-phosphate, which requires the participation of Mg2+ions.
9. Glycerol-2-phosphoric acid converted to phosphoenolpyruvate
Under the catalysis of enolase, glycerate 2-phosphate dehydrates, and the energy inside the molecule redistributes to form phosphoenolpyruvate enol phosphate bond, which is the second high-energy phosphate compound in the glycolysis pathway.
10. Generation of pyruvate
Under the catalysis of pyruvate kinase, the high-energy phosphate group of phosphoenolpyruvate molecule is transferred to ADP to generate ATP, which is the second substrate level phosphorylation reaction in the glycolysis pathway, requiring the participation of Mg2+and K+, and the reaction is irreversible.
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Under normal physiological conditions, various metabolic processes in the human body are strictly and finely regulated to keep the internal environment stable and meet the needs of physiological activities of the body.This regulation and control is mainly achieved by changing the enzyme activity.Hexokinase (glucokinase), phosphofructokinase-1 and pyruvate kinase are key enzymes of glycolysis. Their activity directly affects the speed and direction of the whole metabolic pathway, of which phosphofructokinase-1 is the most important.
1. Hormone regulated insulin can induce the synthesis of GK, PFK-1 and PK, thus enhancing the glycolysis process.
2. The effect of metabolites on rate limiting enzymesAllosteric regulationPhosphofructokinase-1 (PFK-1) is one of threeRate limiting enzymeThe one with the lowest catalytic efficiency is the most important regulation point in the glycolysis pathway.The enzyme molecule is a tetramer.The molecule not only has the binding site with the substrate, but also hasAllosteric activationThe site where an agent binds to an allosteric inhibitor.F-1,6-BP, ADP and AMP are its allosteric activators, while ATP and citric acid are its allosteric inhibitors.Under the joint regulation of these metabolites, the body can adjust the speed of sugar decomposition according to energy demand.When intracellular energy consumption increases, ATP concentration decreases, and AMP and ADP concentrations increase, phosphofructose kinase 1 is activated, sugar decomposition speed is accelerated, and ATP production is increased;WhenCellsWhen there is enough ATP reserve, the concentration of ATP increases, the concentration of AMP and ADP decreases, the phosphofructokinase-1 is inhibited, the speed of sugar decomposition slows down, the amount of ATP generated is reduced, and energy waste is avoided;When hungry, the body mobilizes and stores fat to decompose and oxidize, generating a large amount of acetyl CoA. Acetyl CoA can be condensed with oxaloacetic acid to form citric acid, inhibiting the activity of phosphofructokinase-1, thereby reducing the decomposition of sugar, so as to maintain the concentration of blood sugar under hunger.
Reaction characteristics
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1. There is no oxygen involved in the whole process of glycolysis reaction.
2. Less energy is released in glycolysis reaction.Sugar is metabolized by fermentation, and only incomplete oxidation can occur.
3. There are three rate limiting enzymes in the whole process of glycolysis reaction.In the whole process of glycolysis reaction.Three steps are irreversible.These three steps are catalyzed by three rate limiting enzymes, namely hexokinase, 6-phosphofructokinase-1 and pyruvate kinase.
Physiological significance
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Glycolysis can transfer the released free energy to ATP.Glycolysis is also common to hexoses such as fructose, mannose and galactosedegradationApproaches.Fructose and mannose can be converted into fructose-6-phosphate through the catalytic action of hexokinase, and fructose can also be converted into glyceraldehyde 3-phosphate through the action of a series of enzymes.Galactose can be converted into glucose 1-phosphate catalyzed by some enzymes.Some congenital metabolismdiseaseIt is caused by the loss of some enzymes in the metabolism of fructose and galactose.If phosphate fructose aldolase is absent, fructose-1-phosphate accumulates in the liver, intestine and kidney, causing hepatomegaly and decline of liver kidney and intestinal absorption function. Children with this disease cannot take itfructoseOr sucrose.
Energy conversion
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Equilibrium point
It is worth mentioning that most of the reactions after the formation of fructose 1,6-diphosphate are carried out in the direction of energy increase, and will not be carried out spontaneously without the catalysis of enzymes (PFK, PGK).The reverse process of glycolysis, gluconeogenesis (the production of glucose from non sugar substances such as glycerol), is easy to carry out. This process uses most of the enzymes that have appeared in glycolysis. Except for the two "coachmen" mentioned, they only appear in glycolysis.In the two reverse reactions of gluconeogenesis, a large amount of heat will be released, respectively - 14 and - 24 kJ/mol.
Anaerobic and aerobic environments
In glycolysis, each molecule of glucose provides two molecules of ATP.Mitochondrial energy of eukaryotesmeanwhileAnother 36 molecules of ATP were obtained from two molecules of pyruvic acid.The amount of energy conversion depends on the way NADH+H produced in the cytoplasm passes through the mitochondrial membrane.The process of glycolysis to pyruvate can be carried out in both anaerobic and aerobic environments.Glyceraldehyde 3-phosphate is dehydrogenated by glyceraldehyde 3-phosphate dehydrogenase GAPDH.The removed hydrogen ions will reduce the oxidant (coenzyme) NAD to NADH+H.NAD regenerates in the respiratory chain.If in an oxygen free environment, exothermic（ΔG ´=- 25kJ/mol) Lactose dehydrogenase (LDH) reaction will regenerate NAD: reduction of pyruvate will generate lactose and regenerate NAD (yeast will use the other two enzymes pyruvate decarboxylase plus alcohol dehydrogenase).
The interrelation between GAPDH and LDH reactions of glycolysis in anaerobic environment, except thatpartNADH+H will be converted by glycerol phosphate dehydrogenase (GDH), and most of it will be used to regenerate NAD.
key enzyme
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Key enzymes of glycolysis: There are three enzymes, namely hexokinase, 6-phosphate fructose kinase-1 and pyruvate kinase. The reactions they catalyze are basically irreversible.The regulation modes include allosteric regulation and covalent modification regulation.
1. 6-Phosphofructokinase-1
Fructose-6-phosphate kinase-1 is the most important to regulate the flow of glycolysis pathway, and the pathway of glucolysis is regulated by metamerism.
Regulation of ATP on 6-phosphofructokinase-1: ATP plays an allosteric activation role on 6-phosphofructokinase-1 when the concentration of ATP at the binding site of ATP and 6-phosphofructokinase-1 active center substrate is low.When ATP at the allosteric regulatory site outside the active center is in high concentration, ATP plays an inhibitory role.
Regulation of fructose 2,6-diphosphate on 6-phosphofructokinase-1: fructose 2,6-diphosphate is the strongest allosteric activator of 6-phosphofructokinase-1;Its function is to cancel the allosteric inhibition of ATP and citric acid on 6-phosphofructokinase-1 together with AMP.
2. Pyruvate kinase
Pyruvate kinase is the second important regulation point of glycolysis, which is regulated by allosteric regulation and covalent modification.
Allosteric activator: fructose 1,6-diphosphate
Allosteric inhibitor: ATP, alanine
3. Hexokinase
Hexokinase is regulated by feedback inhibition. Long chain fatty acyl CoA and 6-phosphate glucose will inhibit the activity of hexokinase, and insulin will activate the activity of hexokinase.
The ratio of ATP/AMP plays an important role in regulating the activity of 6-phosphofructokinase-1.When ATP concentration was high, 6-phosphofructokinase-1 was almost inactive, and glycolysis was weakened;When AMP accumulates and ATP is less, enzyme activity recovers and glycolysis strengthens;In addition, H+can also inhibit the activity of 6-phosphofructokinase-1, which canpreventExcess lactic acid is formed in muscles.
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In 1897, German biochemist E. Bishner found that the brewery enzyme leaving the living body had activityin the future, which greatly promoted the research of glucose metabolism in vivo.Within a few years after the discovery of brewing enzyme, it was revealed that glycolysis is a ubiquitous process in animals, plants and micro organisms.British FG. Hopkins discovered in 1907 that muscle contraction was directly related to lactic acid production.British physiologist A5. Hill, a German biochemist, O. Merhoff, O. Warburg and many other scientists have experienced about 20 years, from each specific chemical change and the enzymes, coenzymes needed, as well as chemical energy transmission and other aspectsdiscussIn 1935, it finally clarified the 12 intermediate steps of the transformation from glucose (6 carbon) to lactic acid (3 carbon) or alcohol (2 carbon), and clarified that several enzymes, coenzymes and ATP participated in the reaction in this process.
Clinical significance
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1. Glycolysis is the main physiological way to obtain energy when the body is relatively hypoxic.When an organism is exercising violently or for a long time, its energy demand increases and glycolysis accelerates. At this time, even if the respiration and circulation speed up to increase the supply of oxygen, it still cannot meet the demand. The muscle is in a relatively hypoxic state and must provide urgently needed energy through glycolysis.
2. Glycolysis is an effective way for some tissues to obtain energy in the presence of oxygen. Glycolysis is the only way for mature red blood cells to obtain energy.It is also an effective way for nerve, white blood cell, bone marrow and other tissue cells to obtain part of energy under aerobic conditions.
3. Under pathological conditions, such as respiratory or circulatory dysfunction, severe anemia, massive blood loss, etc., when the body is hypoxic, it will lead to accelerated or even excessive glycolysis, which may lead to lactic acid poisoning due to excessive production of lactic acid.
