Glycogen (C ₆ H ₁ O ₀) n[5]It is a kind of animal starch, also called heparan or glycogen, which is a branched chain polysaccharide combined with glucose. Its glycosidic chain is alpha type.It is a stored polysaccharide of animals.
In mammals, glycogen mainly exists inskeletal muscle(accounting for about 2/3 of the whole body's glycogen) andliver(about 1/3), most other tissues, such as myocardium, kidney, brain, also contain a small amount of glycogen.Glycogen or glycogen analogues are also found in lower animals and some microorganisms (such as fungi).The glycogen structure is similar to amylopectin.[1]
Glycogen is stored in the cytoplasm of liver cells and muscle cells, and its shape is particles of different sizes. When it meets iodine, it becomes brown and soluble in water. Glycogen will be destroyed after the body necrosis. Therefore, fresh samples must be taken and fixed in time.Glycogen is not equal to sugar, but a kind of sugar.Sugar fromHistochemistryThe classification of technology is not consistent with that of biochemistry.From the perspective of histochemistry, saccharides can be divided into polysaccharides, neutral syrup substances, acidic mucus substances, mucin and mucolipids.Polysaccharide mainly refers to glycogen, which is a polymer composed of many glucose molecules with glycosidic bonds.When the body dies, it is quickly decomposed into glucose.
Polysaccharides stored in animal and bacterial cells are completely composed of glucose.In animals, the liver andskeletal muscleThe middle storage is the most abundant, which is equivalent to the role of starch in plants.The synthesis and decomposition of glycogen can be maintained under the catalysis of enzymes in vivoblood sugarAt normal levels, glycogen in bacteria is used for energy and carbon supply.In dry state, it is white amorphous powder, odorless and sweet.It is brownish red with iodine, showing the maximum light absorption at 430-490nm.Partially soluble in waterColloidal solution, insoluble in ethanol.Structure andamylopectinSimilarly, it is mainly α - D-glucose, condensed and dehydrated according to the α (1 → 4) glycosidic bond, and another part of the branch chain is connected by the α (1 → 6) glycosidic bond.Use calculated amylasehydrolysisMaltose and glucose are produced at the same time.Animal liver can be treated with 30% sodium hydroxide and then precipitated with ethanol.
Glycogen is a branched macromolecular polysaccharide composed of multiple glucose, with a molecular weight of 10six-10sevenDalton, up to 10eightDalton is the storage form of sugar in the body. Glucose in the molecule is mainly linked to form a straight chain by α - 1,4-glycosidic bond, and some of it is linked to form a branched chain by α - 1,6-glycosidic bond. Glycogen is mainly stored in muscle and liver. Glycogen in muscle accounts for 1-2% of the total weight of muscle, about 400g, and glycogen in liver accounts for 6-8% of the total weight, about 100g.muscleGlycogen decompositionIt supplies energy for muscle self contraction, and liver glycogen decomposition mainly maintains blood glucose concentration.
Plant and animalamylaseCan act on glycogen, produce maltose anddextrin。stayLiving cellThe degradation of glycogen is from nonReducibilityStart at the end and cut off one by oneGlucosyl, generatingD-glucose-1-phosphoric acid, then throughGlycolysisAnd other ways to further decompose to generate energy and provide the carbon framework needed for the synthesis of other biological molecules.Due to the highly branched structure, about 8-10% of glucose in glycogen molecule is in the available nonRestore EndThis is convenient for a large amount of use in a short time when needed, and quick recovery storage when not needed.For example, during muscle contraction, the energy required in the form of ATP is thousands to tens of thousands of times more than that at rest. These ATP mainly depends on the decomposition of glycogen to provide.Glucose, lactic acid, fatty acid, glycerin, someamino acidThrough appropriateMetabolic pathwayTransformed into stored glycogen;The process of glycogen synthesis from glucose in the body is calledGlycogen productionThe process of producing glucose or glycogen from non sugar substances is calledGluconeogenesis。
The storage or consumption of glycogen in human body is influenced by hormones andsubstrateThe process of control.By regulating the activity of enzymes involved in the process of synthesis and degradation, the glycogen metabolism and blood sugar level of the body can be properly controlled.The abnormal metabolism of glycogen is characterized by glycogen accumulation, which is often due to the lack of related enzymes.For example, glucose-6-phosphataseIn patients with deficiency, the liver and kidney contain a large amount of glycogen with normal structure. The clinical symptoms are hepatomegaly, extreme hypoglycemia, hyperlipemia, hyperuricemia, ketosis, and growth stagnation.
Physicochemical properties
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Chinese name: glycogen
Chinese alias: alpha-1,6-glucan
Molecular Structure Diagram
English name: Glycogen
CAS No.: 9005-79-2
EINECS No.: 232-683-8
Molecular formula: (C ₆ H ₁ O ₀) n
Molecular weight: 666.5777
The molecular structure of glycogen is similar to that of amylopectin.It is mainly composed of D-glucose linked through α - 1,4 to form sugar chains, and branched chains are generated through α - 1,6 links.The glycogen molecule has more branches than amylopectin, and the glucose linked by α - 1 and α - 4 is oneBranch point(The average spacing of amylopectin molecules is about 20-25 glucose).The molecular weight ranges from several million to tens of millions.The purified glycogen is white amorphous particles,ReducibilityExtremely weak, easily soluble in water to produce milky white colloidal solution, with specific rotation of about+200 °, relatively strong resistance to alkali, brown in reaction with iodine, low solubility in alcohol, and ethanol added toaqueous solutionIt can precipitate glycogen.
Fundamentals
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Glycogen is composed of branches or straight chains of D-glucose, which is most abundant in liver and muscle.tooIodateIt is a strong oxidant that can oxidize the ethylene glycol group (CHOH-CHOH) in glucose into two free radicalsAldehyde group(- CHO), free aldehyde group reacts with Schiff's reagent to produce purple red product, and the color depth is proportional to the polysaccharide content.becausemonosaccharideDuring fixation, dehydration, embedding, etcHistochemistryIt is extracted in the process of operation, so the sugars that can be displayed on general tissue samples are mainly polysaccharides, including glycogenMucopolysaccharide, mucin, glycoprotein and glycolipids, etc.Therefore, it is necessary to determine whether the red substance is glycogenControl experiment。Glycogen can beSalivary amylaseHydrolysis: first use salivary amylase to perform PAS color development. If the reaction is negative, it indicates that it is glycogen, otherwise it is other polysaccharides.
synthesis
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Made from glucose (including a small amount offructoseandGalactose）The process of glycogen synthesis is called glycogen synthesis. The reaction is carried out in the cytoplasm and requires ATP and UTP consumption. The synthesis reaction includes the following steps:
Synthetic reaction steps
Glycogen synthesisEnzyme catalysisThe first sugar molecule cannot be synthesized from scratch, and α - 1,4-polydextrose containing at least four glucose residues is required as the primerReducibilityThe terminal reacts with UDPG, and the glucose group C1 on UDPG is notRestore EndC4 forms α - 1,4-glycoside chain, which adds one glucose unit to glycogen. UDPG is the donor of active glucose group, which consumes UTP in the process of generation, so glycogen synthesis is an energy consuming process. Glycogen synthase can only promote α - 1,4-glycoside bond, so this enzymecatalytic reactionIt forms amylose molecules, such as starch, linked by α - 1,4-glycoside bonds.
Glycogen synthesis
There is a special protein in the body called glycogenin, which can be used as the receptor of glucose group. From the beginning, it is like glucose that synthesized the first glycogen molecule. The enzyme that catalyzes this reaction is glycogen initiationsynthetase(glycogen initiator synthesis), and then synthesize an oligosaccharide chain asprimer, then continue byGlycogen synthaseCatalytic synthesis of sugar.At the same time, the formation of glycogen branching chain requiresBranching enzyme(branching enzyme) catalyzes the transfer of 5-8 glucose residue oligosaccharide straight chains to another sugar atom and connects them with α - 1.6-glycoside bonds to form branchessugar chain, when it is notReducibilityThe terminal can continue to be extended by glycogen synthase.Multi branching increases the water solubility of glycogen, which is conducive to its storageGlycogen decompositionIt can start from multiple non reducing ends at the same time to improve the decomposition speed[2]。
In this way, one of the glycogenGlycosylTo 1 molecule glucose, butphosphorylaseIt only acts on the α (1 → 4) glycoside bond on the glycogen, and it will no longer work when it is catalyzed to 4 glucose residues from the α (1 → 6) glycoside bondDebranching enzymeOnly with the participation of (branching enzyme) can glycogen be completely decomposed.Debranching enzyme is a bifunctional enzyme, which catalyzes two reactions of glycogen debranching. The first function is 4 - α-glucan baseTransferases(4 - α - D-glucanotransferase) activity, that is, the triglucan group on the tetraglucan branch chain on glycogen is transferred toEnzyme proteinAnd then give it to the glucose residue with free 4-hydroxy at the end of the same glycogen molecule or adjacent glycogen molecule to generate α (1 → 4) glycosidic bond, resulting in the straight chain extending three glucose (Figure 5-6), while only one glucose residue is left at the α (1 → 6) branch, which is hydrolyzed and removed under the catalysis of another function of the debranching enzyme, namely the activity of 1,6-glucosidase,As free glucose, glycogen can be completely phosphorylated and hydrolyzed under the synergistic and repeated action of phosphorylase and debranching enzyme.
Decomposition of glycogen (Fig. 1)
Decomposition of glycogen (Fig. 2)
Metabolic regulation
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Allosteric regulation of glycogen metabolism
Regulation of glycogen synthesis and decomposition
Glucose 6-phosphate can activate glycogen synthase and stimulate glycogen synthesis. At the same time, it inhibits glycogen phosphorylase and prevents glycogen decomposition. ATP and glucose are also glycogen phosphorylase inhibitors. High concentration of AMP can activate inactive glycogen phosphorylase b to make it active and accelerate glycogen decomposition.Ca2+can be activatedPhosphorylase kinaseAnd then activate phosphorylase to promoteGlycogen decomposition。
Hormone regulation
Adrenaline andGlucagonThe cAMP linked enzymatic reaction can be scaled up step by step to form a control system regulating glycogen synthesis and decomposition.
Inhibition of glycogen synthesis (Fig. 1)
When the body is affected by some factors, such as blood glucose concentration decline and intense activity, it promotes the secretion of adrenaline and glucagon, which are associated with liver or muscle and other tissuesCell membrane receptorBinding, G-protein mediated activationAdenylate cyclase, which makes cAMP generation increase, and cAMP makes cAMP dependentprotein kinase(cAMP dependent protein kinase) activation. On the one hand, activated protein kinaseGlycogen synthaseaPhosphorylationIs inactive glycogen synthase b (Fig. 4-9);The other side phosphorylates inactive phosphorylase kinase into active phosphorylase kinase, and the activated phosphorylase kinase further phosphorylates inactiveGlycogen phosphorylaseB phosphorylation into active glycogen phosphorylase a (Fig. 4? 0), the final result is to inhibit glycogen production and promoteGlycogen decomposition, makeHepatic glycogenIt is decomposed into glucose and released into the blood to increase the blood sugar concentration. Muscle glycogen is decomposed for muscle contraction[3]。
Inhibition of glycogen synthesis (Fig. 2)
Generative action
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It refers to the process of synthesizing glycogen from glucose and other monosaccharides in the organism.byGlycogen decompositionThe reverse process of.It is more common to use low molecular lactose, etcGlycolysisThe process of producing glycogen is calledGluconeogenesisThe difference is based on information.Animals are mainly carried out in the liver or muscle, which is a major process of energy storage.After food digestion, glucose in the blood is inhaled by the digestive organ and transported to the liver through the portal vein of the liver, where it is first absorbed by hexokinase and ATPPhosphorylationIt is converted into 6-phosphate glucose, and then converted into UDP glucose through 1-phosphate glucoseGlycogen synthaseGlycogen is generated under the action of.At this time, α - 1,4-glycoside bond is formed, but its α - 1,6 bond is calledDebranching enzymeA transformation ofGlycosidaseIs formed under the synergistic effect of.In addition, in order to cause this reaction, a small amount of polysaccharide (such as glycogen itself) is needed as the primer.This reaction is also carried out in yeast and other microorganismshigher plantThe storage of starch and the formation of polysaccharides by bacteria are also similar.However, due to different organisms, their enzymes and reaction pathways are somewhat different.Animals and plants use glucose and sucrose as energy sources of tissues and important components of body fluids respectively. The normal function of tissues is carried out under the good regulation of the concentration level of these substances, and glycogen synthesis is of great significance in this regulation.
application
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Sugar——carbohydrateIs the most importantEnergy supply material, mainly in the form of glucose.Glucose is oxidized rapidly to supply energy.Sugar is also an important raw material for the body and participates in various activities of cells.Such as sugar andprotein synthesisGlycoproteins are components of antibodies, enzymes and hormones.Synthesis of sugars and lipidsGlycolipids。It is the raw material of cell membrane and nerve tissue.Sugar has a special role in maintaining function.SugarDetoxification。When the liver glycogen reserves are sufficient, it can enhance the resistance, and food supplies sufficient sugar, which can reduce the consumption of protein as energy supply.
The liver is an important organ for regulating blood glucose concentration.The original glycogen in the liver accounts for about 5~6% of the liver weight, and the average glycogen in adults is about 100g.When a large amount of sugar food is ingested for a long time, the liver glycogen can reach about 150 grams, and even 150~200 grams for healthy fat people. When hungry for more than 10 hours, most of the liver glycogen is consumed.
When blood sugar is too low or appetite disappears, glucose can be taken orally or intravenously.After oral administration, glucose is absorbed through the portal vein and directly enters the liver, which is more favorable than intravenous infusion.If the glucose tolerance of patients with liver disease is reduced, but the blood sugar is increased, and there is hepatogenic diabetes, it is not appropriate to inject glucose intravenously, nor is it necessary toOral glucose。
Patients with liver disease should be supplied with sufficient sugar to ensure the need for protein and heat, so as to promote the repair and regeneration of liver cells.Enough glycogen storage in the liver can enhance the resistance of the liver to infection and toxins, protect the liver from further damage, and promote the recovery of liver function.However, the glycogen storage in the liver has a certain limit, too much glucose can not be supplied, and too much glycogen can not be synthesized. Therefore, the emphasis on limiting excess calories to cause obesity is of vital importance to liver disease.
The significance of diet therapy lies in that, according to their own disease and nutrition, they choose supplementary food to improve the function of human organs. All kinds of food will play a certain role in certain organs of the human body.If the diet is appropriate, it can maintain physiological balance. It is generally believed that rice, noodles, meat and eggs are mostlyAcidic foodVegetables and fruits are mostly alkaline. Proper conditioning is conducive to the acid-base balance of human metabolism.
Patients with liver disease or those with hypertension, arteriosclerosis and obesity should eat less animal fat, and fish, shrimp and lean meat should be used when eating meat;People who usually have weak spleen and stomach can eat more white lentils and bean products, because these foods are rich in protein and can regulate and enhance the function of the digestive system.Understand the basic nutrients and taste of each food, and realize the true meaning of self recuperation[4]。
Related diseases
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Glycogen accumulation disease
1. Introduction
Glycogen accumulation diseaseIt is a kind of glycogen metabolism disorders caused by congenital enzyme defects, most of which belong toAutosomal recessive inheritance, the incidence varies from race to race.According to European data, its incidence is 1/(20000~25000).Glycogen synthesis andCatabolismThere are at least 8 kinds of necessary enzymes in the. There are 12 types of clinical diseases caused by these enzyme defects, of which type I, III, IV, VI, IX are mainly liver diseases;Type Ⅱ, Ⅴ and Ⅶ are mainly muscle tissue damage.This kind of disease has a common biochemical feature, that is, abnormal glycogen storage, most of which is the increase of glycogen storage in liver, muscle, kidney and other tissues.Only a few disease species have normal glycogen storage, but the molecular structure of glycogen is abnormal.
2. Etiology
Glycogen is a high molecular polysaccharide composed of glucose units, which is mainly stored in liver and muscle as standby energy. Normal liver and muscle contain about 4% and 2% glycogen respectively.Glucose in human bodyGlucokinase, glucophosphate mutase andUridine diphosphate glucosePyrophosphorylaseFormed under the catalysis ofUridine diphosphate glucose（UDPG）。Then byGlycogen synthaseConnect the glucose molecule provided by UDPG into a long chain with α - 1,4-glycosidic bond;Every 3-5 glucose residues are composed ofBranching enzymeThe glucose connected at positions 1 and 4 is transferred to positions 1 and 6 to form branches. If it is expanded, it will eventually form dendrimer.The molecular weight of glycogen is more than millions, and its outermost glucose straight chain is longer, mostly 10-15 glucose units.Glycogen decomposition is mainly catalyzed by phosphorylase, which releases glucose 1-phosphate from glycogen molecules.However, the role of phosphorylase is limited to 1,4 glycosidic bonds, and when there are only 4 glucose residues before the branching point, three of them must be transferred to other straight chains by debranching enzymes (amyol-1, 6-glucosidase) to ensure the continuous role of phosphorylase.At the same time, the debranching enzyme can release a glucose molecule linked by the α - l, 6-glycoside bond, and this repeated operation will ensure the body's demand for glucose.Exists inlysosomeα - 1,4 glucosidase (acidicMaltase）It can also hydrolyze glucose linear chains of different lengths to make them into oligosaccharides such as maltose.GSD is due to the lack of any enzyme defect in the process of glycogen synthesis and decomposition, which causes glycogen synthesis or decomposition to be blocked, resulting in glycogen deposition in tissues and causing disease.Due to the different types of enzyme defects, there are many types of glycogen metabolic diseases. See the table for common types.Type Ⅰ, Ⅲ, Ⅵ and Ⅸ are mainly liver lesions, and type Ⅱ, Ⅴ and Ⅶ are mainly muscle tissue damage.
3. Symptom diagnosis
The disease is a hereditary disease, and the child has hepatomegaly at birth.With the growth of age, obvious hypoglycemia symptoms such as weakness, sweating, vomiting, convulsion and coma may occurketoacidosis。
The child has slow growth and development, no mental disorder, short stature, obesity, yellowish skin, swollen abdomen, significantly enlarged liver, hard texture, poor muscle development, weakness, especially in the lower limbs.Most patients with this disease cannot survive to adulthood and often die of acidosis coma.Mild cases can be improved in adulthood.The disease can be divided into more than ten subtypes, of which type I is the most common.
The disease should be differentiated from diabetes:
Diabetic patients also have symptoms of acidosis and hypoglycemia, but the typical symptoms of diabetic patients are "more than three and less", that is, drinking more, urinating more, eating more and losing weight, which can be identified according to the secondary symptoms.
4. Treatment
Use a high protein and high glucose diet and feed it for many times to maintain normal blood sugar level, especially once at midnight to avoid hypoglycemia in the next morning.Other treatments include preventing infection and correcting acidosis (NaHCO3 can be used and sodium lactate is prohibited).If the blood lipid continues to rise after correcting hypoglycemia, 50 mg/(kg · d) of antomin can be used.hyperuricemiaIf dietary therapy cannot be controlled, allopurinol 5~10mg/(kg · d) can be used.Hormone treatment is beneficial to maintain normal blood sugar level and improve appetite.Glucagon, various steroid hormonesthyroxineIt has a temporary effect on improving symptoms.Surgical methods, such as portal vena cava anastomosis, can make the glucose absorbed by the intestine cross the liver and enter the blood circulation directly. The liver may shrink and grow faster after surgery, but the long-term effect is not sure.There are also reports of liver transplantation, the effect is unknown and difficult to promote.Others used enzyme replacement therapy, but the effect was not good.
Glycogen accumulationType IV: no specific treatment for glycogen, high protein and low sugar diet, and corn oil can not preventcirrhosisProcess.No definite effect was obtained with purified glucosamine.The extract of Aspergillus can sharply reduce the liver glycogen, so it is a promising therapeutic method.In addition, liver transplantation can be performed.
In a word, diet treatment and symptomatic treatment are mainly used for this disease, so that the child can survive the infancy, because the body gradually adapts to other diseases after the age of 4Metabolic pathway, clinical symptoms can be alleviated.
Glycogen storage disease type I
Disease characteristics: Type I glycogen storage disease (GSD1) is characterized by the accumulation of glycogen and fat in the liver and kidney, leading to hepatomegaly and nephromegaly.Some untreated newborns have severe hypoglycemia;The more common symptoms of untreated newborns are hepatomegalyLactic acidosisHyperuricemia, hyperlipidemia and/or hypoglycemic epilepsy.Sick children usually have fat baby faces with two cheeks, relatively thin limbs, short stature and protruding abdomen.Xanthoma and diarrhea may also occur.Platelet dysfunction may lead to bleeding tendency of frequent epistaxis.Untreated GSDIb in the first few years of life with neutrophil and monocyte dysfunction and chronicNeutropenia, which can lead to recurrent bacterial infection and oral and intestinal ulcer.Long term complications of untreated GSD1 include growth retardation and its resulting short stature, osteoporosis, delayed puberty, gout, kidney diseasePulmonary hypertensionHepatic adenoma, polycystic ovary, pancreatitis and changes in brain function with a tendency to deteriorate.Children receiving treatment should have normal growth and adolescence.Many patients survive to adulthood.
Diagnosis/detection: The diagnosis of GSD1 is based on clinical manifestations, abnormal blood/plasma glucose, lactose, uric acid, triglyceride and lipid concentrations, and molecular genetic blood detection.The mutation of G6PC gene (GSD1a) causes 80% of GSD1;The mutation of SLC37A4 gene (GSD1b) results in 20% of GSD1.For these two genesmolecular geneticsTesting is available clinically.
Treatment: treatment of symptoms: medical nutrition therapy is used to maintain normal glucose concentration, prevent hypoglycemia, and provide optimal nutrition for growth and development.When dietary therapy cannot completely control the concentration of uric acid in blood, allopurinol is used to prevent gout;Lipid lowering drugs should be used if the lipid level still rises under metabolic control;Supplement citrate to help prevent the development of urinary stones or improve renal calcinosis;useAngiotensin converting enzyme(ACE) inhibitors for microalbuminuria;Renal transplantation was used to treat end-stage renal disease;Surgical or other intervention, such as subcutaneousalcoholInjection and radiofrequency ablation for hepatic adenoma;Liver transplantation should be carried out for patients who do not respond to medical measures or have hepatocellular carcinoma at the same time;With humansGranulocyte colony stimulating factor(G-CSF) to treat recurrent infection of GSD1b.Prevention of complications: improve hyperuricemia and hyperlipidemia, maintain normal renal function and prevent kidney disease.Monitoring: After the age of ten, the kidney and liver were examined by ultrasound every year;Every 3-6 months after the discovery of liver adenomaUltrasonography of liver。Drugs/conditions to avoid: fructose and sucrose in diet should be low;The intake of galactose and lactose should be limited to one dose per day.Detection of high-risk blood relatives: molecular genetic blood detection (if the family specific mutation is known) and/or evaluation by a metabolic doctor after birth (if the family specific mutation is unknown) can help early diagnosis and treatment of high-risk siblings of GSD1.
