Fat metabolism

biochemical reaction

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Fat metabolism is important and complex in the body biochemical reaction It refers to the process of digestion, absorption, synthesis and decomposition of the fat in the organism with the help of various related enzymes, and the processing of the fat into substances needed by the organism to ensure the operation of normal physiological functions Life activities It is of great significance. lipid It is the body's energy storage and Energy supply The important substance of Biomembrane Important structural components of. The diseases caused by abnormal fat metabolism are common in modern society.

The digestion of fat is mainly in the upper part of the small intestine through various enzymes and bile acid Action of salt, hydrolysis to glycerol , fatty acids, etc. There are two kinds of absorption of lipids: medium chain Short chain fatty acids Constitutive triglyceride emulsification Then it can be absorbed via portal vein Blood transfusion; Long chain fatty acids The composition of triglycerides and Apolipoprotein 、 cholesterol Isojunction synthesis Chyle microparticle And finally enter the blood through lymph.

Metabolized in the body after fat absorption Biochemical process Mainly divided into: triglycerides phospholipid , cholesterol Plasma Lipoprotein Four categories lipid The metabolism of substances is affected by insulin 、 Glucagon 、 Dietary nutrition , Biochemistry in vivo enzymatic activity Such complex and precise regulation can be transformed into the material components required by various fine biochemical reactions of the body. Liver adipose tissue The small intestine is an important place for fat synthesis, and the liver has the strongest capacity for fat synthesis. After synthesis, it should be combined with apolipoprotein, cholesterol, etc Very low density lipoprotein (VLDL) into the blood and transported to extrahepatic tissues for storage or utilization. If the triglycerides synthesized by the liver cannot be transported in time, they will form Fatty liver 。 In case of long-term hunger and insufficient sugar supply, fatty acids are used in large quantities to generate Acetyl CoA Oxidation provides energy and generates a large number of ketones. The liver is the organ that generates ketone bodies, but it cannot use ketone bodies. Brain tissue Fatty acids cannot be used, while ketones are soluble in water, with small molecules, and can be passed through blood brain barrier 。 serious diabetes patient, glucose Without effective utilization, fatty acids are converted into a large number of ketones, which exceeds the capacity of extrahepatic tissue to use, causing the rise of ketones in blood, which can cause ketoacidosis 。

Chinese name: Fat metabolism

Main parts: Cytoplasmic matrix, mitochondria, endoplasmic reticulum, peroxisomes
Main metabolic pathways: Glycolysis 、 Tricarboxylic acid cycle β - oxidation, citric acid cycle

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lipid It mainly includes the following 4 types:

Fat metabolism

Fat: It is synthesized by glycerol and fatty acid. There are two sources of fatty acid in the body: one is the body's own synthesis, and the other is food supply, especially some Unsaturated fatty acid ， organism Unable to synthesize, weigh Essential fatty acids , such as linoleic acid 、 α - linolenic acid 。

metabolize

phospholipid : composed of glycerin and fatty acid phosphoric acid and Nitrogenous compound Build.

Sphingolipids : fat combined by sheathing acid and fatty acid, which is said to contain phosphoric acid Sphingomyelin , those containing sugar are called Glycosphingolipid 。

Cholesterol fat: It is formed by the combination of cholesterol and fatty acids.

The digestion of fat is mainly in the upper part of the small intestine through various enzymes and bile acid The function of salt is to hydrolyze into glycerol, fatty acid, etc. Absorption of lipids includes two situations: medium chain Short chain fatty acids Constituted triglycerides emulsification Then it can be absorbed. The absorbed triglycerides are hydrolyzed into fatty acids and glycerol in intestinal mucosa cells, and finally portal vein Blood transfusion; Triglycerides composed of long-chain fatty acids are decomposed into long-chain fatty acids and Monoglyceride After reabsorption, triglycerides are synthesized from intestinal mucosa cells, and Apolipoprotein , cholesterol, etc Chyle microparticle And finally enter the blood through lymph.

Triglyceride metabolism

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Anabolism

triglyceride It is the energy storage and oxidation of the body Energy supply An important form of.

1. Synthetic parts and raw materials

Soybean products promote fat metabolism

Liver adipose tissue The small intestine is an important place for synthesis, and the synthesis ability of liver is the strongest. Note: Hepatocyte It can synthesize fat, but cannot store fat. After synthesis Apolipoprotein 、 cholesterol Isojunction synthesis Very low density lipoprotein , into blood and transported to extrahepatic tissues for storage or utilization. If hepatosynthetic triglyceride Failure to transport in time will result in Fatty liver 。 fat cells It is a warehouse for the body to synthesize and store fat.

synthesis glycerol Glycerol and fatty acid required by triester are mainly from grape Carbohydrate metabolism Yes. Glycerin is composed of Glycolysis Generated Dihydroxyacetone phosphate It is converted into fatty acid from sugar Oxidative decomposition Generated Acetyl CoA synthesis.

2. Basic process of synthesis

① Monoglyceride Pathway: This is the way that small intestinal mucosal cells synthesize fat, which is synthesized by monoglyceride and fatty acid triglyceride 。

② Diacylglycerol Pathway: Synthetic pathway of hepatocytes and adipocytes.

Adipocyte deficiency Glycerol kinase Therefore, it cannot be used Free glycerol , can only use the 3 provided by glucose metabolism- Glycerol phosphate 。

Catabolism

mean Fat mobilization , on fat cells within Hormone sensitivity Under the action of the enzyme of sexual triglyceride Lipolysis It is fatty acid and glycerin and released into Blood supply Oxidation of other tissues.

Glycerol, glycerol stimulation → glycerol 3-phosphate → dihydroxyacetone phosphate → glycolysis or Aerobic oxidation Energy supply can also be converted into sugar;

Fatty acids, and albumin Combined with transport into various tissues Beta oxidation Energy supply.

Catabolism of fatty acids - β - oxidation

stay Oxygen supply Under sufficient conditions, fatty acids can be decomposed into acetyl CoA, which can be completely oxidized to CO two And H two O and release a lot of energy. Most tissues can oxidize fatty acids, but Brain tissue Exceptions, because fatty acids cannot pass blood brain barrier 。 The specific oxidation steps are as follows:

1. Fatty acids are activated to form acyl CoA.

2. Fatty acyl CoA entering mitochondrion , because β - oxidation of fatty acids It is carried out in mitochondria. This step requires carnitine Transshipment. Carnitine acyltransferase I is a fatty acid Beta oxidation Of Rate limiting enzyme Fatty acyl CoA enters mitochondria as fatty acid Beta oxidation Main points of Speed limit steps If the sugar supply is insufficient when hungry enzymatic activity enhance, Fatty acid oxidation Enhanced, the body is powered by fatty acids.

3. β - oxidation of fatty acids, basic process (see the original book)

Butyryl CoA undergoes the last β oxidation to generate 2 molecules of acetyl CoA

Therefore, each time β oxidizes 1 molecule of fatty acyl CoA to generate 1 molecule of FADH two , 1 molecule NADH+H+, 1 molecule acetyl CoA, via respiratory chain Oxidation of the former generates 1.5 molecules of ATP, and the latter generates 2.5 molecules of ATP.

4. Energy generation of fatty acid oxidation

Fatty acids and glucose Different, its energy generation is different from its content carbon atom Number related, because each fatty acid Molecular size The amount of ATP generated varies with Palmitic acid As an example; 1 molecule palmitic acid contains 16 carbon atoms, 7 times Beta oxidation Generate 7 molecules of NADH+H+and 7 molecules of FADH two , 8 molecules of acetyl CoA, and 2 molecules of ATP are required for all fatty acid activation. Therefore, molecular 1 palmitic acid is completely oxidized and co generated:

7 × 2.5+7 × 1.5+8 × 10-2=106 molecular ATP

By weight, fatty acids produce more energy than glucose.

Other oxidation modes of fatty acids

1． Unsaturated fatty acid Oxidation of: also mitochondrion Proceed with the Saturated fatty acid The difference is that the cis and trans bond are different. Through mutual transformation between isomers Beta oxidation 。

2. Peroxisome fatty acid oxidation: It is mainly to oxidize the 20 carbon and 22 carbon fatty acids that cannot enter the mitochondria into shorter fatty acids, so that they can enter the mitochondria for decomposition and oxidation, which is invalid for shorter bond fatty acids.

3. Including Conjugated double bond Of Polyunsaturated fatty acids Oxidation: unlike ordinary unsaturated fatty acids, conjugation improves the stability of this structure, making it impossible for organisms to pass isomerase Transfer double bond, so it needs to be disconnected by restoring Conjugate system , and then isomerize.

4． Side chain Fatty acid oxidation: after Alpha oxidation Move the β - side chain blocking β - oxidation to the α - position, and then carry out β - oxidation to generate monoacyl CoA.

5. Degradation of odd carbon acyl CoA: propionyl CoA is produced by β - oxidation, and then Carboxylation reaction And two-step isomerization to Succinyl CoA entry Tricarboxylic acid cycle Further oxidation.

Formation and utilization of ketone bodies

Ketone bodies include Acetoacetic acid 、 β - hydroxybutyric acid 、 acetone 。 Ketone body is a special intermediate metabolite of fatty acids during liver decomposition and oxidation mitochondrion in Beta oxidation In addition to oxidative phosphorylation to provide energy, a large amount of acetyl CoA generated can also synthesize ketones. But the liver cannot use ketone bodies because it lacks the ability to use ketone bodies Enzyme system 。

1. Generation process: the liver will Acetyl CoA After three steps of reaction, it is converted to acetoacetic acid, and then through β - hydroxybutyric acid dehydrogenase It is converted into β - hydroxybutyric acid and transported to the outside of liver for decomposition and utilization. Acetoacetic acid can be decarboxylated spontaneously to form acetone that is difficult for the body to use. Acetone is toxic and generally diffused through the lungs.

2. Utilization: The ketone body generated by liver is transported to extrahepatic tissues through blood for further decomposition and oxidation.

The liver is the organ that generates ketone bodies, but it cannot use ketone bodies. The extrahepatic tissue cannot generate ketone bodies, but it can use ketone bodies.

3. Physiological significance

In case of long-term hunger and insufficient sugar supply, fatty acids are used in large quantities to generate acetyl CoA for oxidation and energy supply, but brain tissue cannot use fatty acids because they cannot pass through the blood-brain barrier, and ketones are soluble in water and small molecules can pass through the blood-brain barrier. Therefore, the synthetic ketones in the liver increase and are transported to the brain for energy supply. But under normal circumstances, the blood ketone body content is very low.

serious diabetes In patients, glucose is not effectively used, and fatty acids are converted into a large number of ketones, which exceeds the capacity of extrahepatic tissue to use, causing the rise of ketones in blood, which can cause ketoacidosis 。

4. Regulation of ketone body production

① 1 ″ When the food is full or the sugar supply is sufficient: insulin Increased secretion, Fat mobilization The ketone body production is reduced; 2″ Carbohydrate metabolism Wangsheng 3 -? Glycerol phosphate and ATP are sufficient, fatty acid lipoification increases, oxidation decreases, ketone body generation decreases; Acetyl CoA and citric acid Energy allosteric activation Acetyl CoA carboxylase , promote the synthesis of malonyl CoA, which can inhibit carnitine Lipoyltransferase I, blocking Beta oxidation The production of ketone body is reduced.

② In contrast to the above, ketone body production increases in patients with hunger or insufficient sugar supply or diabetes.

Fatty acid anabolism

1. Fatty acids are mainly synthesized from acetyl CoA. All substances that produce acetyl CoA in metabolism are Synthetic fatty acids Fatty acids can be synthesized in various tissues of the body. Liver is the main place, Fatty acid synthase System exists in mitochondrion In exocytosis. But acetyl CoA is not easy to penetrate mitochondrial membrane , so we need Shuttle system Acetyl CoA is transported to the cytosol mainly through Citrate pyruvate cycle To complete.

The synthesis of fatty acids also requires ATP NADPH All required hydrogen is provided by NADPH, which is mainly from pentose phosphate pathway 。

2. Synthesis process of palmitic acid

Acetyl CoA carboxylase is synthesized from fatty acid Rate limiting enzyme , exists in the cytoplasm, Cofactor by Biotin 。 Citric acid Isocitrate Is its allosteric structure activator , so after a full meal, Carbohydrate metabolism Vigorous, citric acid during metabolism can activate this enzyme to promote the synthesis of fatty acid, and palmitoyl CoA is its allosteric inhibitor , reduce fatty acid synthesis. This enzyme also has Covalent modification ， Glucagon adopt Covalent modification Inhibit its activity.

② Synthesis from acetyl CoA and malonyl CoA Long chain fatty acids In fact, it is a repeated lengthening process, with 2 lengthens at a time carbon atom , by fatty acid synthesis Multienzyme system catalysis. mammal The active enzyme is Dimer The dimer will lose its activity when depolymerized. Each subunit has ACP and Cofactor In the process of synthesis, the acyl group is attached to the auxiliary group. Butyryl is the first round product catalyzed by fatty acid synthase. Through the first round of condensation, reduction, dehydration, reduction and other steps between acetyl CoA and malonyl CoA, the C atom is increased by two, and then malonyl CoA is used as carbon source Continue the above reaction, add 2 C atoms each time, and after 7 cycles, palmitic acid with 16 carbon atoms can be generated.

3. Acid Carbon chain Lengthening of

Carbon chain elongation in hepatocytes Endoplasmic reticulum or mitochondrion At Palmitic acid On the basis of, it can generate fatty acids with longer carbon chains.

4. Regulation of fatty acid synthesis (see the original book for the process)

insulin Inducing acetyl CoA carboxylase Fatty acid synthase It can promote the synthesis of fatty acids and also promote the entry of fatty acids adipose tissue , accelerate the synthesis of fat. and Glucagon 、 adrenaline 、 auxin Inhibits fatty acid synthesis.

Important derivatives of polyunsaturated fatty acids

prostaglandin 、 thromboxane 、 leukotriene All by Polyunsaturated fatty acids Derived from, in the adjustment Cellular metabolism It plays an important role in inflammation, immunity, allergy and Cardiovascular disease Equal importance Pathological process of Stimulated by hormones or other factors, Membranous lipid from phospholipase A2 catalytic hydrolysis, release Arachidonic acid , arachidonic acid in lipid Peroxidase Under the action of cycloperoxidase, it can produce prostaglandin and thromboxane.

phospholipids metabolism

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contain phosphoric acid Of lipid Phospholipids can be divided into two categories: glycerol Composed phospholipid scale Glycerophospholipid , by Sphingosine Constitutive scale Sphingomyelin 。

Glycerophospholipid metabolism

Glycerophospholipid is composed of one molecule of glycerol, two molecules of fatty acid and one molecule of phosphoric acid Arachidonic acid Due to the different substituents connected with phosphoric acid, it can also be divided into phosphatidylcholine（ lecithin ）Phosphatidylethanolamine（ Cephalin ）, 2 Phosphatidylglycerol （ Cardiolipin ）Etc.

1． Glycerophospholipid Synthesis of

① Synthetic parts and raw materials

It can be synthesized in all tissues of the body, and liver, kidney and other tissues are the most active Endoplasmic reticulum Upper synthesis. Glycerol and fatty acid used for synthesis are mainly used Carbohydrate metabolism Transformed. Secondary Polyunsaturated fatty acids It often depends on food supply and synthesis ATP 、CTP。

② Synthesis process

Phosphatidic acid It is the precursor for the synthesis of various glycerol phospholipids, and there are two main synthesis routes:

1″ Diacylglycerol Synthetic route: Cephalin , lecithin is synthesized by this way, and diacylglycerol is used as Intermediate product , by CDP choline Phosphoric acid and Substituent 。

2 ″ CDP diacylglycerol pathway: Inositol phospholipid ， Cardiolipin Thus, CDP diacylglycerol is used as the intermediate product and inositol And other substituents.

2． Glycerophospholipid Degradation of

Mainly in the body phospholipase Catalytic hydrolysis process. among Phospholipase A ? 2 can hydrolyze the second ester bond in glycerol phospholipid molecule, and the product is lysophospholipids and Unsaturated fatty acid , most of which are Arachidonic acid , Ca2+is the activator 。 This lysophospholipids is a kind of strong Surfactant , can make cell membrane Destruction causes hemolysis or Cell necrosis 。 Premenstrual Hemolytic phospholipase After continuous hydrolysis, the effect of dissolving cell membrane will be lost.

metabolism of sphingophospholipid

The main structure is Sphingosine One molecule of sphingosine is usually connected with one molecule of fatty acid amide Chains, not ester bonds. Add 1 molecule of phosphoric acid containing group or Glycosyl , the former is linked with sphingosine by ester bond to form sphingomyelin, and the latter by β - Glycosidic bond Connected into Glycosphingolipid , the most abundant Sphingomyelin That is, with Choline phosphate , fatty acid and sphingosine.

1． Anabolism

with Brain tissue Most active, mainly in Endoplasmic reticulum conduct. Reaction process Pyridoxal phosphate, NADPH+H+, etc. required coenzyme The basic raw materials are palmitoyl CoA and serine 。

2. Degradation and metabolism

By the action of sphingomyelinase (belonging to phospholipase C) phosphate Bond hydrolysis Choline phosphate and ceramide (N-lipoylsphingosine). Lack of this enzyme can cause sphingomyelin deposition diseases such as dementia.

Cholesterol metabolism

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Anabolism

1. Almost all tissues of the body can be synthesized. The liver is the main site, and synthesis is mainly in the cytosol and Endoplasmic reticulum In.

2. Synthetic raw material acetyl CoA is synthetic cholesterol Because acetyl CoA is mitochondrion It is similar to the fatty acid synthesis mentioned above, and it must pass citric acid —— pyruvic acid Circulate into the cytosol. In addition, a large amount of NADPH+H+and ATP 。 The synthesis of 1 molecule cholesterol requires 18 molecules of acetyl CoA, 36 molecules of ATP and 16 molecules of NADPH+H+. Acetyl CoA and ATP mostly come from mitochondria Aerobic oxidation of sugar And NADPH is mainly from the Pentose phosphate pathway 。

3. Synthesis process

In short, it can be divided into three stages.

① Mevalonate （ MVA ）Synthesis of HMGCoA: firstly, HMGCoA is synthesized in the cytosol, which is the same as that of ketone body. But in mitochondrion HMGCoA in HMGCoA Lysase Ketone bodies are generated under catalysis, while HMGCoA generated in the cytosol is Endoplasmic reticulum HMGCoA reductase Catalyzed by NADPH +Hydrogen is supplied by H+, and MVA is generated by reduction. HMGCoA reductase It's synthetic cholesterol Rate limiting enzyme 。

② Squalene Synthesis of MVA: MVA is composed of ATP Energy supply , in a series of Enzyme catalysis Next, squalene of 3OC is generated.

③ Cholesterol synthesis: After multi-step reaction, squalene removes three methyl groups to generate 27C cholesterol.

4. Adjustment

HMGCoA reductase It is the rate limiting enzyme for cholesterol synthesis. Many factors regulate cholesterol mainly through enzymatic activity To achieve.

② Cholesterol: OK Feedback suppression Synthesis of cholesterol.

③ Hormones: insulin It can induce the synthesis of HMGCoA reductase, increase the synthesis of cholesterol, Glucagon and cortisol On the contrary.

Cholesterol conversion

1. Convert to bile acid This is the main part of cholesterol metabolism in the body Go 。

2. Convert to Sterols Hormone, cholesterol is adrenal cortex , ovary, etc Steroid hormone The raw material of this hormone includes Glucocorticoid and sex hormone 。

3. Convert to 7-dehydrocholesterol In the skin, cholesterol is oxidized to 7-dehydrocholesterol, and then UV irradiation Change to VitD3.

Plasma Lipoprotein Metabolism

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Plasma Lipoprotein Classification

1． Electrophoretic method : You can change Lipoprotein It is divided into prebeta, beta lipoprotein and Chyle microparticle （CM）。

2. Ultracentrifugation: divided into chyle particles Low density lipoprotein (VLDL), low density lipoprotein (LDL) and High density lipoprotein (HDL) are equivalent to Electrophoretic separation CM, prebeta, beta, and alpha lipoproteins.

Plasma Lipoprotein Composition

Plasma Lipoprotein Mainly by protein 、 triglyceride , phospholipids, cholesterol and their esters. free fatty acids He Qing protein binding However, transportation does not belong to plasma lipoproteins. CM is the largest, with the most triglycerides and the least protein, so the density is the smallest. VLDL also contains more triglycerides, but its protein content is higher than that of CM. LDL contains cholesterol and Cholesterol ester Most. HDL contains the most protein.

Structure of lipoproteins

Plasma various Lipoprotein Have roughly similar Basic structure 。 Hydrophobicity Stronger triglycerides and cholesterol esters are located in the core of lipoproteins, while Apolipoprotein , phospholipid and Free cholesterol Isoamphiphilic molecules are characterized by Molecular layer Covering the surface of lipoproteins, its non-polar orientation is inward and connected with the internal hydrophobic core Polar group Facing outward, lipoprotein molecules are spherical. CM and VLDL are mainly based on triglycerides, while LDL and HDL are mainly based on Cholesterol ester Is the kernel. Because the polar groups of lipoprotein molecules toward the surface are hydrophilic, the Hydrophilicity , so that it can be evenly dispersed in the blood. From CM to HDL, the diameter is getting smaller and smaller, so the proportion of the outer layer is increasing, so HDL contains apolipoprotein and phospholipid is the highest.

Apolipoprotein

Lipoprotein The protein part in Apolipoprotein , mainly including apoA, B, C, D and E. Different lipoproteins contain different apolipoproteins. Apolipoproteins are bisexual molecules, Hydrophobic amino acid Form non-polar surface, Hydrophilicity amino acid It is a polar surface. Its nonpolar surface is connected with the hydrophobic lipid core to make the structure of lipoproteins more stable.

metabolize

1. Chylose particles

The main function is to transport Exogenous triglyceride And cholesterol. Fasting There is no CM in the blood. After digestion and absorption of exogenous triglycerides, they are re synthesized in small intestinal mucosal cells, and Apolipoprotein It forms CM and is transported to extrahepatic tissues through lymph and blood Lipoprotein lipase Under the action, triglycerides are hydrolyzed, the products are used by extrahepatic tissues, and CM residues are absorbed and used by the liver.

2． Very low density lipoprotein

VLDL is transportation endogenous The main form of triglycerides. Triglycerides, apolipoproteins, cholesterol, etc. synthesized by hepatocytes and small intestinal mucosal cells themselves form VLDL, which is secreted into blood lipase Hydrolysis utilization, VLDL and HDL during hydrolysis Mutual exchange , VLDL becomes IDL It is absorbed and metabolized by the liver, and the unexposed IDL continues to become LDL.

3． Low density lipoprotein

LDL in human plasma is transformed from VLDL, which is the main form of transporting endogenous cholesterol synthesized by liver. Liver is the main organ that degrades LDL Histiocyte Existence of membrane surface LDL receptor , can absorb LDL, in which the cholesterol fat is hydrolyzed into free cholesterol and fatty acid, and the hydrolyzed free cholesterol can Suppressor cell The synthesis of cholesterol reduces the further uptake of LDL by cells, and promotes the esterification of free cholesterol to be stored in the cytosol. This reaction is Endoplasmic reticulum Fatty acyl CoA cholesterol fatty acyltransferase (ACAT) catalyzed by. In addition to the LDL receptor pathway, LDL in plasma can also be cleared by the mononuclear phagocyte system.

4． High density lipoprotein

The main function is Reverse transshipment cholesterol And transport cholesterol from extrahepatic tissues to liver metabolism. After the newborn HDL is released into the blood, it will transform the cholesterol and its esters in the body from CM and VLDL to HDL. Plasma plays a major role in this process Lecithin cholesterol acyltransferase （ LCAT ）Finally, newborn HDL becomes mature HDL, and mature HDL and liver cell membrane HDL receptor binding is uptake, in which cholesterol synthesis bile Acids may be discharged from the body through bile, so that cholesterol in the senescent cell membrane in the peripheral tissue can be transported to the liver for metabolism and discharged from the body.

Hyperlipidemia

When the blood lipid is higher than the upper limit of normal people Hyperlipidemia , represented by Triglyceride , cholesterol content increases, which is shown in Lipoprotein CM, VLDL and LDL can all increase, but HDL generally does not increase.

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