Lipid substances include fats and lipids. Fat, also known as triglycerides, consists of glycerol and fatty acids. Lipids include cholesterol and its esters, phospholipids and glycolipids. Lipid is an important part of cytoplasm and cell membrane; Lipid metabolism is closely related to sugar metabolism and the metabolism of some amino acids. Fat is a good energy source for the body, its potential is 1 times higher than that of the same amount of protein or sugar, and it can provide abundant heat energy for the body through oxidation. Sterol is the precursor of some hormones, vitamin D and cholic acid. Lipid metabolism is closely related to some human diseases (such as ketosis, ketonuria, fatty liver, hyperlipidemia, obesity and atherosclerosis, coronary heart disease, etc.). ), so lipid metabolism is of great significance to human health.

I. Digestion and absorption of lipids

1. Digestion and absorption of fat The fat in food is not digested in the mouth and stomach. Because there is no lipase in saliva, although there is a small amount of lipase in gastric juice, the pH value in gastric juice is 1 ~ 2, which is not suitable for lipase. The digestion of fat is mainly carried out in the small intestine. Due to intestinal peristalsis and emulsification of bile salts, fat is dispersed into fine micelles, which increases the contact surface with lipase. Fat is converted into monoglycerides, diglycerides, fatty acids and glycerol by digestion, and forms mixed micelles with cholesterol, phospholipids and bile salts. Monoglycerides, diglycerides and fatty acids are absorbed when mixed micelles contact with intestinal mucosal epithelial cells in upper duodenum and jejunum, which is a simple diffusion effect dependent on concentration gradient. After absorption, short-chain fatty acids enter the liver from the blood through the portal vein; Long-chain fatty acids, monoglycerides and diglycerides re-synthesize triglycerides on the endoplasmic reticulum of intestinal mucosal cells, and then form chylomicrons with phospholipids, cholesterol, cholesterol esters and apolipoproteins, which enter the blood circulation through lymphatic vessels.

2. Digestion and absorption of lipids The absorption sites of cholesterol in food are mainly jejunum and ileum, and free cholesterol can be directly absorbed; Cholesterol ester is emulsified by bile acid salt, and then hydrolyzed by cholesterol esterase to produce free cholesterol, which is absorbed. Cholesterol absorbed into intestinal mucosal cells is esterified into cholesterol esters. Cholesterol esters are mostly mixed with chyle particles, and a small amount of them participate in the formation of very low density lipoprotein and enter the blood circulation through lymph. Phospholipids in food are hydrolyzed into fatty acids, glycerol, phosphoric acid, choline or cholamine under the action of phospholipase. After being absorbed by intestinal mucosa, complete phospholipid molecules are re-synthesized in the intestinal wall, which participates in the formation of chylous particles and enters the blood circulation.

Second, the metabolism of fat.

1. Synthesis of fatty acids There are two sources of fatty acids in the body: one is the body's own synthesis, which is stored in adipose tissue in the form of fat and mobilized from adipose tissue when necessary. Saturated fatty acids are mainly synthesized by the body itself; Another source is the supply of food fat, especially some unsaturated fatty acids, which cannot be synthesized by animals themselves and need to be taken from vegetable oil. They are indispensable nutrients for animals, so they are called essential fatty acids. It is also the precursor of physiologically active substances such as prostaglandin, thromboxane and leukotriene. Prostaglandins can dilate blood vessels, lower blood pressure and inhibit platelet aggregation. On the other hand, thromboxane has procoagulant effect. Leukotrienes can cause bronchial smooth muscle contraction, which is related to allergic reaction.

The biosynthesis of fatty acids is catalyzed by multi-enzyme complex system in cytoplasm. The raw materials mainly come from acetic acid coenzyme A and reduced coenzyme II produced by glycolysis, and finally palmitic acid is synthesized. Palmitic acid reacts with malonyl coenzyme A and acetic acid coenzyme A in endoplasmic reticulum and mitochondria respectively, which can extend the carboxyl end of carbon chain to 18 ~ 26℃. Under the catalysis of desaturase, the body can also synthesize unsaturated fatty acids from raw materials such as palmitic acid and stearic acid, but it cannot synthesize essential fatty acids such as linoleic acid, linolenic acid and arachidonic acid.

2. Synthesis of Fat There are two ways to synthesize fat in the body. One is to use the fat in food to transform into human fat, and the other is to transform sugar into fat. Fat is the main source of fat in the body and the process of storing energy in the body. Dihydroxyacetone phosphate produced by glucose metabolism is converted into glycerophosphate in fat and muscle, which reacts with fatty acyl-CoA synthesized by the body itself or activated by two molecules of fatty acids supplied by food to generate phosphatidic acid, then dephosphorylates to generate diglycerides, and then reacts with another molecule of fatty acyl-CoA to generate triglycerides.

3. Decomposition of fat Triglycerides stored in adipose tissue are decomposed into glycerol and fatty acids under the catalysis of hormone-sensitive lipase, which are transported to various tissues throughout the body for utilization. Glycerol is phosphorylated and converted into dihydroxyacetone phosphate, which is metabolized by glycolytic pathway. The fatty acids in the cytosol are first activated to fatty acyl-CoA, and then carried by carnitine into the matrix through the inner membrane of mitochondria for oxidation, and the generated acetyl-CoA enters the tricarboxylase cycle for complete oxidation, which is an important energy source in the body.

4. Generation and utilization of ketone bodies When fatty acids are decomposed and oxidized in the liver, unique intermediate metabolites-ketone bodies, including acetoacetic acid, hydroxybutyric acid and acetone, are produced, which are synthesized by acetyl coenzyme A in the liver. The liver itself cannot use ketone bodies, which are transported to other tissues through blood to provide energy for extrahepatic tissues. Under normal circumstances, the production and utilization of ketone bodies are balanced.

Third, the metabolism of lipids.

1. Metabolism of cholesterol Cholesterol is mainly synthesized in liver cells. Cholesterol cannot be completely oxidized and decomposed in the body, but it can be converted into many bioactive substances. Adrenal cortical hormone, androgen and estrogen are all synthesized from cholesterol in the corresponding endocrine gland cells. Cholesterol is converted into bile salts in the liver, which is discharged into the digestive tract with bile and participates in the digestion and absorption of lipids. 7- deoxycholesterol in skin can be converted into vitamin under ultraviolet irradiation, and the latter can be converted into the active form of 1, 25- by hydroxylation in liver and kidney, which participates in calcium and phosphorus metabolism.

2. Metabolism of phospholipids Lipids containing phosphoric acid are called phospholipids, and phospholipids composed of glycerol are collectively called glycerophosphates, including lecithin and cephalin, which are the basic skeleton of the bilayer structure of biofilm lipids, and the constant content is fixed lipids. Lecithin is an important component in the synthesis of plasma lipoprotein. Phosphatidyl composed of sphingosine is called sphingomyelin, which is an important component of biofilm and participates in cell recognition and information transmission. Phosphoric acid is the precursor of phospholipid synthesis, which generates diglycerides under the action of phosphatase, and then reacts with CDP- choline or CDP- cholamine to generate lecithin and cephalin. Sphingosine is formed by the reaction of palmitic acid coenzyme A and serine. Sphingosine is acylated by long-chain acyl coenzyme A to form N- acid sphingosine, that is ceramide, which further reacts with CDP- choline to form sphingomyelin.

Fourthly, plasma lipoprotein metabolism.

1. Composition and content of blood lipids Lipids contained in plasma are collectively referred to as blood lipids, and their composition includes triglycerides, phospholipids, cholesterol and its esters, free fatty acids, etc. There are two sources of blood lipids: one is exogenous, and the lipids ingested from food are digested and absorbed into the blood; The second is endogenous, synthesized by tissues such as liver and fat cells, and released into the blood. Blood lipids are influenced by diet, age, sex, occupation and metabolism, and fluctuate greatly. See table 1.2 ~ 24 h for the composition and content of blood lipids in normal people.

Table 1 composition and content of lipids in fasting plasma of normal adults

Lipid nanomole/liter mg/dl

The total fat content is 4 ~ 7 (g/L) 400 ~ 700.

Triglyceride 0.11~1.7610 ~160.

The total cholesterol is 3.75 ~ 6.25 150 ~ 250.

Phospholipid 1.80 ~ 3.20

0.3-0.98-25 of free fatty acid

The normal range of lipids in plasma varies with different determination methods. In addition, compared with the whole body lipid, the blood lipid content only accounts for a small part, but all lipids are transported to various tissues through blood. Therefore, the content of blood lipids can reflect the general situation of lipid metabolism.

The sources and ways of blood lipids are as follows:

2. Classification, composition and function of plasma lipoproteins Although there are many lipids in human plasma, they are still clear and transparent, indicating that blood lipids do not exist in a free state in plasma, but combine with protein in plasma and are transported in the form of plasma lipoproteins. Apolipoprotein mainly includes apoA, apoB, apoC, apoD, apoE, and several subtypes. Plasma lipoproteins are spherical particles with polar molecules and hydrophilic groups on the surface and nonpolar molecules and hydrophobic groups on the core. The density, particle size, surface charge, electrophoretic behavior and immunity of various plasma lipoproteins are different, because their lipid and protein mass are different. Generally, they are divided into four categories by ultracentrifugation and electrophoresis, which correspond to each other, namely HDL high density lipoprotein (lipoprotein), VLDL very low density lipoprotein (pro-lipoprotein), LDL low density lipoprotein (lipoprotein) and CM chylomicron. CM is synthesized in jejunal mucosal cells and transports exogenous fat. VLDL synthesizes and transports endogenous fat in hepatocytes. LDL is converted from VLDL in plasma and transports cholesterol to various tissues. HDL is synthesized in hepatocytes and transports cholesterol and phospholipids to the liver.

Five, common diseases caused by lipid metabolism disorder

1. When the diseases caused by abnormal plasma lipoprotein are normal, the plasma lipid level is in dynamic balance and can be kept in a stable range. If the blood lipid level rises on an empty stomach and exceeds the normal range, it is called hyperlipidemia. Because blood lipid exists in the form of lipoprotein, the plasma lipoprotein level will also increase, which is called hyperlipoproteinemia. According to the international tentative classification standard of hyperlipoproteinemia, hyperlipoproteinemia is divided into 6 types, and the changes of plasma lipoprotein and lipid content of each type of hyperlipoproteinemia are shown in Table 2.

Table 2 Changes of plasma lipoprotein and lipid content of different types of high lipoprotein

type

Changes of plasma lipoprotein

Changes of blood lipid content

incidence rate

Ⅰ

Hyperchylomicrobial blood

Elevated triglycerides

Rarely seen

(Increased chylomicrons)

Elevated cholesterol

ⅱa

hyerlipoproteinemia

Triglycerides are normal

ordinary

(Elevated low-density lipoprotein)

Elevated cholesterol

ⅱb

hyerlipoproteinemia

Elevated triglycerides

ordinary

hyerlipoproteinemia

Elevated cholesterol

(Low density lipoprotein and polarity

Elevated low density lipoprotein

Ⅲ

hyerlipoproteinemia

Elevated triglycerides

fewer/ lesser

hyerlipoproteinemia

Elevated cholesterol

("Wide" lipoprotein appears.

Elevated low density lipoprotein

Ⅳ

hyerlipoproteinemia

Elevated triglycerides

ordinary

(Elevated very low density lipoprotein)

Elevated cholesterol

Ⅴ

Hyperchylomicrobial blood

Elevated triglycerides

hyerlipoproteinemia

Elevated cholesterol

distinctive

According to the etiology, it can be divided into primary hyperlipidemia and secondary hyperlipidemia. Primary hyperlipoproteinemia is a disorder of lipoprotein metabolism caused by gene defect, and the common types are Ⅱ A and Ⅳ. Secondary hyperlipoproteinemia is a disorder of lipoprotein metabolism caused by liver, kidney disease or diabetes.

The reason of hyperlipoproteinemia may be the disorder of lipid metabolism caused by the defect of apolipoprotein, lipoprotein receptor or key enzyme of lipoprotein metabolism. Include excessive lipid production, impaired degradation and transport, or both, such as decreased lipoprotein lipase activity, excessive cholesterol intake, excessive cholesterol synthesis in the liver, choline deficiency, blocked bile acid salt synthesis and enhanced fat mobilization in the body. , can cause hyperlipidemia. Atherosclerosis is one of the common diseases that seriously endanger human health. The main reason is the increase of plasma cholesterol, which is deposited on the intima of large and medium arteries. Its pathogenesis is closely related to plasma lipoprotein metabolism. It has been proved that the increase of low density lipoprotein and very low density lipoprotein can promote the occurrence of atherosclerosis, while high density lipoprotein can prevent the occurrence of lesions. This is because high-density lipoprotein can compete with low-density lipoprotein for receptors on vascular smooth muscle cell membrane, which inhibits the ability of cells to absorb low-density lipoprotein, thus preventing the accumulation of low-density lipoprotein in vascular endothelial cells. Therefore, in the prevention and treatment of atherosclerosis, drugs that reduce low density lipoprotein and very low density lipoprotein and increase high density lipoprotein can be considered. Obese and diabetic patients have low plasma HDL levels, so they are prone to coronary heart disease.

2. In general, ketonemia, ketonuria and acidosis, the content of ketone bodies in blood is very small, usually less than 1mg/ 100mL. The content of ketone bodies in urine is so small that it can't be measured by ordinary methods. However, when you have diabetes, the use of sugar is blocked or you can't eat for a long time, the energy your body needs can't be obtained from the oxidation of sugar, so fat is mobilized in large quantities and fatty acids in your liver are oxidized in large quantities. When the ketone bodies produced in the liver exceed the available limit of extrahepatic tissues, the ketone bodies in the blood accumulate, which is called "ketonemia" clinically. Patients excrete a large number of ketone bodies with urine, that is, "ketonuria." Acetoacetic acid and hydroxybutyric acid in ketone bodies are acidic substances, and excessive accumulation in the body will affect the blood pH and cause "acidosis".

3. Fatty liver and liver cirrhosis, due to disorder of glucose metabolism, a large amount of fat in adipose tissue is mobilized, or liver function is damaged, or due to insufficient supply of lecithin, an important raw material for lipoprotein synthesis, or methionine and betaine contained in choline, liver lipoprotein synthesis cannot be shipped out in time, resulting in fat accumulation in liver cells, occupying a large space, affecting liver function, and the liver fat content exceeds 10%, thus forming ". A large amount of fat accumulates and even destroys many liver cells, which makes connective tissue proliferate and leads to "cirrhosis".

4. Cholesterol and atherosclerosis Although cholesterol is an integral part of the cell membrane of higher eukaryotic cells and is necessary for cell growth and development, the increase of serum cholesterol level will often increase the incidence of atherosclerosis. The formation and development of atherosclerotic plaque is related to the disorder of lipid metabolism, especially cholesterol metabolism. Cholesterol overeating, hypothyroidism, nephrotic syndrome, biliary obstruction and diabetes often lead to hypercholesterolemia.

In recent years, it has been found that the mutation of hereditary apolipoprotein (APO) gene leads to the imperfection of exogenous cholesterol transport system and the abnormal ratio of low density lipoprotein to high density lipoprotein in plasma. For example, the deficiency of APO AI and APO CIII leads to low HDL in blood, and the mutation of APO-E-2 gene leads to hyperlipoproteinemia. In this case, the cholesterol content in food will affect the cholesterol content in blood, so patients should be treated by controlling the cholesterol in diet. Another cause of atherosclerosis is the genetic defect of low density lipoprotein receptor gene. Low density lipoprotein can't send cholesterol to cells for degradation, so the degradation of endogenous cholesterol is hindered, which leads to the increase of cholesterol in plasma.

5. Obesity Obesity is a disease with high incidence. Mild obesity has no obvious symptoms of consciousness, while obesity will appear fatigue, palpitation, shortness of breath, poor endurance, and is prone to diabetes, atherosclerosis, hypertension and coronary heart disease. Except for a few cases of obesity caused by endocrine disorders, most cases are caused by nutritional disorders. Because the calorie intake of food is greater than the needs of human activities, people who have too much fat deposition and weigh more than 20% are called obese. To prevent obesity, it is necessary to apply a reasonable diet, especially to control the intake of sugar and fat, and active and moderate exercise is the most effective prescription to lose weight.

Fat is the main energy storage substance in human body, and more than 50% of the energy needed by human body is supplied by fat oxidation; Fat also assists the absorption of fat-soluble vitamins, so fat is one of the important nutrients in human body; Lipids, including cholesterol, cholesterol esters and phospholipids, are widely distributed in all tissues of the body and are the main substances that constitute biofilm. They combine with many enzyme proteins on the membrane to play the role of membrane. Cholesterol is also an important substance for synthesizing bile acids, vitamins and steroids in the body. Lipid metabolism is influenced by many factors, especially neurohumors, such as adrenaline, growth hormone, glucagon, adrenocorticotropic hormone, glucocorticoid, thyroxine and thyrotropin, which promote fatty acid release from adipose tissue, while insulin and prostaglandin have opposite effects. Proper intake of food containing lipids and proper physical exercise are beneficial to maintain normal lipid metabolism. Once a certain factor changes and causes abnormal lipid metabolism, it will lead to diseases and endanger human health.