What is Glycolysis?

The main physiological function of sugar is to provide the body with the energy required for life activities. Sugar catabolism is the main way for an organism to obtain energy. There are three main pathways for oxidative decomposition of sugars in organisms: anaerobic oxidation of sugars, aerobic oxidation of sugars, and pentose phosphate pathways. Among them, the anaerobic oxidation of sugar is also called glycolysis. Glucose or glycogen is degraded into lactic acid and produces a small amount of ATP under anaerobic or hypoxic conditions. This process is basically similar to the process of yeast fermentation of glucosamine, so it is called glycolysis. A series of enzymes that catalyze the glycolysis reaction exist in the cytoplasm, so the entire reaction process of glycolysis occurs in the cytoplasm. Glycolysis is a common stage that all organisms must go through for glucose catabolism.

Basic Information

Chinese name

Glycolysis

Foreign name

glycolysis

Biochemistry

Anaerobic respiration glucose

Stage

Activation phase and energy release phase

Overview of glycolytic substances

Under anaerobic conditions, the way to obtain energy from the catabolic metabolism of sugar is also a preparation way for most organisms to perform aerobic oxidation of glucose. In this process, six carbon glucose molecules are split into two molecules of three carbon pyruvate after more than ten steps of enzyme-catalyzed reaction, and two molecules of adenosine diphosphate (ADP) and inorganic phosphate (Pi) are combined to form two molecules. Adenosine triphosphate (ATP).

The further metabolism of pyruvate has different paths due to the different species and the supply of oxygen. For example, under anaerobic conditions, strongly contracted animal muscle cells, pyruvate is reduced to lactic acid, which can be broken down into ethanol or acetic acid in many microorganisms; under aerobic conditions, it is oxidized to carbon dioxide and water.

Glycolysis reaction process

Glycolysis is a process that starts from the decomposition of glucose to generate pyruvate. There are 10 steps of enzyme-catalyzed reaction in the whole process.

Glucose phosphorylation

The first step in glycolysis is the hexokinase-catalyzed glucose C6 to phosphorylate to form glucose 6-phosphate. This kinase requires Mg2 + as a cofactor and consumes a molecule of ATP at the same time. This reaction is irreversible.

Isomerization of 2.6-phosphate glucose to 6-phosphate fructose

This is an aldose-ketose isomerization reaction. This reaction is catalyzed by the hexose phosphate isomerase to catalyze the isomerization of aldose and ketose, and requires the participation of Mg2 + ions. The reaction is reversible.

Phosphorylation of 3.6-phosphate fructose to 1,6-diphosphate fructose

This reaction is phosphofructokinase-catalyzed phosphorylation of fructose 6-phosphate to produce fructose 1,6-diphosphate, which consumes a second ATP molecule.

4.1, 6-Diphosphate fructose cleavage

Under the action of aldolase, the bond between fructose hexose 1,6-bisphosphate C3 and C4 is broken, and one molecule of glyceraldehyde 3-phosphate and one molecule of dihydroxyacetone phosphate are generated.

5.3-Interconversion of glyceraldehyde phosphate and dihydroxyacetone phosphate

Glyceraldehyde 3-phosphate is the substrate for the next step of the fermentation, so dihydroxyacetone phosphate needs to be converted to glyceraldehyde 3-phosphate under the catalysis of triose phosphate isomerase in order to further ferment.

6.3-Glycerol phosphate oxidation

In the presence of NAD + and H3P04, glyceraldehyde 3-phosphate is catalyzed by glyceraldehyde 3-phosphate dehydrogenase to produce 1,3-diphosphate glycerate. This step is the only oxidation reaction in the fermentation.

7.1,3-Diphosphoglycerate converted to 3-phosphoglycerate

Under the action of phosphoglycerate kinase, 1,3-bisphosphoglycerate high-energy phosphoryl is transferred to ADP to form ATP and 3-phosphoglycerate.

8. Glycerate-3-phosphate is converted to glycerate-2-phosphate

Under the catalysis of phosphoglycerate mutase, the phosphate group of C3 in the glycerate-3-phosphate molecule is transferred to C2 to form glycerate-2-phosphate, which requires the participation of Mg2 + ions.

9. Conversion of glyceric acid-2-phosphate to phosphoenolpyruvate

Under the enolase catalysis, glycerate-2-phosphate is dehydrated and the internal energy of the molecule is redistributed to form a phosphoenolpyruvate enol phosphate bond, which is the second high-energy phosphate compound in the glycolytic pathway.

10. Pyruvate production

Under the catalysis of pyruvate kinase, the transfer of high-energy phosphate groups of phosphoenolpyruvate molecules to ADP to generate ATP is the second substrate level phosphorylation reaction of the glycolytic pathway, which requires the participation of Mg2 + and K +, and the reaction is irreversible.

Glycolytic regulation

Under normal physiological conditions, various metabolic processes in the human body are strictly and finely regulated to keep the internal environment stable and to meet the needs of the body's physiological activities. This regulatory control is mainly achieved by changing the activity of the enzyme. Hexokinase (glucokinase), phosphofructokinase-1, and pyruvate kinase are the key enzymes of glycolysis. Their activity directly affects the speed and direction of the entire metabolic pathway. Among them, 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. Allosteric regulation of metabolites on rate-limiting enzymes Phosphofructokinase-1 (PFK-1) is the least catalytically efficient of the three rate-limiting enzymes, and is therefore the most important regulatory point in the glycolytic pathway. The enzyme molecule is a tetramer. The molecule has not only a site that binds to a substrate, but also a site that binds to an allosteric activator and an allosteric inhibitor. F-1,6-BP, ADP, and AMP are allosteric activators, while ATP and citric acid are allosteric inhibitors. Under the joint regulation of these metabolites, the body can adjust the rate of sugar breakdown according to energy requirements. When the energy consumption in the cell increases, the ATP concentration decreases, and the AMP and ADP concentrations increase, the phosphofructokinase-1 is activated, the sugar decomposition rate is accelerated, and the ATP production is increased; when there is sufficient ATP reserve in the cell, the ATP concentration increases , AMP and ADP concentrations decrease, phosphofructokinase-1 is inhibited, the rate of sugar decomposition is slowed, ATP generation is reduced, and energy waste is avoided; when starved, the body mobilizes stored fat to decompose and oxidize, generating a large amount of acetyl CoA. Condensation with oxaloacetate to citric acid inhibits the activity of phosphofructokinase-1, thereby reducing the breakdown of sugars to maintain blood glucose concentration under starvation.

Characteristics of glycolytic reaction

1. There is no oxygen involved in the whole process of glycolysis reaction.

2. Less energy is released in the glycolysis reaction. Sugar is metabolized by fermentation, and only incomplete oxidation can occur.

3. There are 3 rate-limiting enzymes in the whole process of glycolysis reaction. Throughout the glycolysis reaction. There are three steps that are irreversible reactions. These three steps are catalyzed by three rate-limiting enzymes: hexokinase, 6-phosphofructokinase-1, and pyruvate kinase.

Glycolysis physiological significance

Glycolysis can transfer the released free energy into ATP. Glycolysis is also a common degradation pathway of fructose, mannose, galactose and other hexoses. Fructose and mannose can be converted into fructose-6-phosphate through the catalytic action of hexokinase. Fructose can also be converted into glyceraldehyde 3-phosphate through the action of a series of enzymes. Galactose can be converted to glucose 1-phosphate by some enzymes. Some congenital metabolic diseases are caused by the absence of certain enzymes in the above-mentioned fructose and galactose metabolism. If phosphofructoaldolase is missing, fructose-1-phosphate accumulates in the liver, intestine, and kidney, causing liver enlargement and decline in liver, kidney, and intestinal absorption. Children with this disease cannot take fructose or sucrose.

Glycolytic energy conversion

balance point

It is worth mentioning that most of the reactions after the production of fructose 1,6-diphosphate proceed in the direction of increasing energy, without the catalysis of enzymes (phosphofructokinase (PFK), phosphoglycerate kinase (PGK)) , It will not happen spontaneously. The reverse process of glycolysis-gluconeogenesis (producing 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 "carmen" mentioned Besides, they only appear in glycolysis. In the two-step reverse reaction of gluconeogenesis, a large amount of heat is released, which are -14 and -24kJ / mol, respectively.

Anaerobic and aerobic environments

In glycolysis, two molecules of ATP are provided per molecule of glucose. Eukaryotic mitochondria can simultaneously obtain another 36 molecules of ATP from two molecules of pyruvate. How much energy is converted depends on how the NADH + H produced in the cytoplasm passes through the mitochondrial membrane. Whether in anaerobic or aerobic environment, the process of glycolysis to pyruvate can proceed. Glyceraldehyde 3-phosphate is dehydrogenated by GAPDH, a glyceraldehyde 3-phosphate dehydrogenase. The removed hydrogen ions reduce the oxidant (coenzyme) NAD to NADH + H. NAD regenerates in the respiratory chain. In an anaerobic environment, the exothermic (G & acute; =-25kJ / mol) lactose dehydrogenase (LDH) reaction regenerates NAD: reduction of pyruvate generates lactose and regenerates NAD (yeast uses two other enzymes Pyruvate decarboxylase plus ethanol dehydrogenase).
The glycolytic GAPDH- and LDH-reactions in the anaerobic environment are interconnected. Except for a small amount of NADH + H which is converted by phosphoglycerol dehydrogenase (GDH), most of them are used to regenerate NAD.

The importance of glycolysis

The 6-phosphofructokinase-1> pyruvate kinase> hexokinase ATP / AMP ratio has important significance for the regulation of 6-phosphofructokinase-1 activity. When the ATP concentration is high, the 6-phosphate fructokinase-1 is almost inactive and the glycolysis is weakened; when AMP is accumulated and the ATP is less, the enzyme activity is restored and the glycolysis is strengthened; in addition, H + can also inhibit 6 -Phosphofructokinase-1 activity, which prevents excessive lactic acid formation in muscle.

Glycolysis Discovery

In 1897, the German biochemist E. Bischner discovered that the enzyme leaving the living body had activity, which greatly promoted the study of sugar metabolism in the body. Within a few years after the discovery of zymogenase, glycolysis was revealed to be a common process in animals and plants and microorganisms. FG Hopkins in Britain equaled the discovery in 1907 that muscle contraction is directly related to lactic acid production. British physiologist AV Hill, German biochemist O. Mayrhof, O. Warburg and many other scientists have experienced about 20 years, from each specific chemical change and the enzymes, coenzymes and chemistry needed Various aspects such as energy transfer were discussed. In 1935, the twelve intermediate steps of the transformation from glucose (6 carbons) to lactic acid (3 carbons) or alcohol (2 carbons) were finally clarified, and several types of processes were clarified in this process. Enzymes, coenzymes and ATP participate in the reaction.

Clinical significance of glycolysis

1. Glycolysis is the main way to obtain energy physiologically when the body is relatively hypoxic. When the organism is exercising vigorously or for a long time, energy demand increases and glycolysis accelerates. At this time, even if breathing and circulation are accelerated to increase the supply of oxygen, it still cannot meet the needs. The muscle is in a relatively hypoxic state and must pass glycolysis Solutions provide much-needed energy.

2. Glycolysis is an effective way for certain tissues to obtain energy when aerobic, and glycolysis is the only way for mature red blood cells to obtain energy. It is also an effective way for nerves, white blood cells, bone marrow and other tissue cells to obtain some energy under aerobic conditions.

3. In pathological conditions, such as respiratory or circulatory dysfunction, severe anemia, massive blood loss, etc., when the body is hypoxic, it can cause accelerated or even excessive glycolysis, which can cause lactic acidosis due to excessive lactic acid production.