The role of liver in lipid metabolism

The liver plays a key role in the regulation of lipid metabolism. The liver synthesizes bile acids, with the deficiency of which there is practically no digestion of fats. Liver enzyme systems are capable to catalyze the majority of reactions of lipid metabolism. Enzymatic reactions of synthesis of triglycerides in the liver and adipose tissue are similar. Synthesized triglycerides in the liver are either remain in the liver, or secreted into the blood in the form of lipoproteins - VLDL and HDL. In conditions of glucose excess in hepatocytes there is the synthesis of triglycerides and phospholipids from fatty acids, which enter the liver from the intestine. At a high content of fatty acids in the plasma their uptake by liver is increased, triglyceride synthesis and fatty acid oxidation are enhanced, and production of ketone bodies is increased. Ketone bodies are delivered from the liver into muscles, kidneys, brain, etc. with the bloodstream, where they are oxidized. At deficiency of glucose there is oxidation of fatty acids in the liver.

For the synthesis of phospholipids choline or compounds which are donors of methyl groups, which are involved in the formation of choline (eg, methionine) are necessary. If there is insufficient intake or formation of choline phospholipid synthesis ceases or slows down, and neutral fat is stored in the liver. Fatty liver infiltration can change into fatty liver dystrophy.

Cholesterol metabolism. Part of the cholesterol comes from food, but much more quantity of it is synthesized in the liver from acetate. The biosynthesis of cholesterol in the liver is inhibited by exogenous cholesterol, i.e., is regulated by the principle of negative feedback.

The effect of exogenous cholesterol on its biosynthesis in the liver is associated with inhibition of -hydroxy--methylglutaryl-CoA-reductase reaction:

Cholesterol is synthesized most in the liver. And splitting of cholesterol is also in the liver. Part of the cholesterol is excreted with the bile in unchanged form in the intestine, but most of the cholesterol - 75% is converted into bile acids.

In the liver, cholesterol can react with fatty acids to form cholesterol esters. The resulting esters enter the blood, which also contains a certain amount of free cholesterol. In the liver, cholesterol is synthesized by lecithin-cholesterol acyltransferase (LCAT), catalyzing the esterification of cholesterol in the blood plasma.

All the steroid hormones are formed from cholesterol: glucocorticoids, mineralocorticoids, sex hormones. Only 3% of cholesterol is used for all steroid hormones.

Such hormones as insulin, ACTH, pituitary diabetogenic factor, glucocorticoids affect on fat metabolism in the liver. The action of insulin promotes fat storage in the liver. The action of ACTH, diabetogenic factor, glucocorticoids is directly opposite.

Determination of cholesterol in the blood helps to some extent, to talk about the liver function. Cholesterolsynthesized function of the liver and bile acids synthesis function are sufficiently stable to a variety of acute liver injury. During parenchymal liver damage synthetic activity of its cells is weakened, and the concentration of cholesterol and especially its esters in the blood is decreased. In obstructive jaundice the function of liver cells is not compromised vary mach, and the excretion of cholesterol with bile is reduced, which leads to an increase of total cholesterol in blood.

Hypocholesterolemia is observed in severe chronic liver disease, including far gone forms of liver cirrhosis and CAH (chronic active hepatitis). In severe liver damage there are situations when it does not manage to convert fatty acids with short chain (4-8 carbon atoms), they accumulate in the blood serum, providing highly toxic effect on the brain.

Corticosteroids and sex hormones in the liver are converted into 17-ketosteroids, which are excreted in the urine. Conversion of testosterone to estradiol is possible in the liver under the influence of aromatase. Increased activity of this enzyme plays an important role in the "estrogenisation" during cirrhosis of the liver and obesity. In severe liver diseases, the conversion of steroid hormones in 17-ketosteroids can be violated, the amount of ketosteroids in the urine is reduced and the unaltered steroid hormones increased. Elevation of aldosterone content in blood is one of the causes of edema in severe liver disfunctions.

The most pronounced disorders of lipid metabolism (hyperlipidemia, elevated levels of bile acids, cholesterol, -lipoproteins, at least - triglycerides) are observed in alcoholic liver disease, characterized by increased fat transport and synthesis of lipoproteins, inhibition of lipoprotein lipase activity.

Vitamins. All fat-soluble vitamins (A, D, E, K, etc.) are absorbed in the intestinal walls only in the presence of bile acids secreted by the liver. Some vitamins (А, В₁, Р, Е, К, РР, etc.) are deposited by the liver. Many of them are involved in chemical reactions occurring in the liver (В₁, В₂, В₅, В₁₂, С, К, etc.). A part of the vitamins is activated in the liver, being exposed to phosphorylation (В₁, В₂, В₆, etc.).