The main reactions of hepatic metabolism, their significance

Biochemical reactions leaked in the liver, it is converted to the laboratory. It is where the pathways of protein, carbohydrate and lipid metabolism intersect. Detoxification of xenobiotics , alcohol gives it the value of a protective barrier. It participates in the synthesis of the most important blood proteins, hormones, and Violation of one of the links in metabolic reactions leads to severe consequences for the whole organism.

Metabolism hemoprotein

Protein- heme compounds are called hemoproteins . This group includes blood hemoglobin, cytochrome system, muscle myoglobin. Hemoglobin is more important. The decomposition of other substances is not so pronounced due to their small amount.

After the death of old erythrocytes in the spleen, heme and amino acid residues are released . Heme loses iron, which will be used for the synthesis of new hemoglobin, and itself becomes biliverdin, then under the action of special enzymes – bilirubin. It enters the bloodstream and binds to albumin, which delivers it to the liver. Hepatocytes capture toxic indirect bilirubin, conjugate it with glucuronic acid and excrete it with bile. During digestion, it enters the intestines, where urobilinogen is formed from bilirubin . Part of it is absorbed back and enters the kidneys, the other part forms biliverdin, which repeats the metabolic cycle. The third part goes further through the intestines, where  metabolized to stercobilin , and then excreted in the feces.

Glycogen metabolism

The storage form of glucose in the body is represented by glycogen. It is a branched polymer that does not bind water. If the cells were to store directly glucose, which forms bonds with water molecules, their osmotic pressure would increase, the cells decay from oversaturation with moisture. Glycogen is deposited by the liver and muscles, but only the hepatic fraction is used to maintain blood glucose concentration.

The synthesis begins 1-2 hours after the intake of carbohydrates and proceeds with energy costs. With the participation of ATP, glucose is converted into glucose-6-phosphate, then UDP-glucose is formed through a series of irreversible reactions. Its glucose residue is used to attach to the glycogen branch.

In a cell, glycogen never breaks down completely, there is always a small branch to which glucose molecules attach, and its storage occurs. The breakdown occurs between meals, and increases with physical exertion. This process does not require energy costs. Sequentially, with the help of biochemical reactions, the terminal glucose molecules are cleaved. The irreversibility of synthesis and decay reactions ensures their regulation.

Lipid metabolism

Hepatocytes are saturated with enzymes for complete lipid metabolism. Decay reactions take place in mitochondria and lysosomes of cells, synthesis – in the cytosol. All metabolic pathways converge on acetyl- CoA . Its formation occurs after the catabolism of amino acids, the processing of pyruvate and the oxidative processes of fatty acids. This substance combines the metabolic pathways of glucose, lipids and proteins. During reactions based on acetyl- CoA , fatty acids, ketone bodies, cholesterol are produced . It is the substrate of the Krebs cycle, at the end of which water and energy are generated.

During meals, bile is secreted into the duodenum. It emulsifies the ingested fats to ensure their transport through the intestinal wall. In the form of chylomicrons , fat is supplied to hepatocytes . Already in the capillaries, they decompose to fatty acids and glycerol . The first ones penetrate to hepatocytes and are used for the synthesis of triacylglycerols and phospholipids.

Fatty acids can be oxidized by mitochondria to form acetyl- CoA , which is used for the Krebs cycle. When there is a lack of oxaloacetate , the synthesis of ketone bodies begins, which will serve as a substrate for energy starvation for other tissues.

Cholesterol is the precursor to steroids, bile acids and vitamin D3 . It is synthesized by the liver based on fatty acids. Production is inhibited by excess blood cholesterol and bile acid levels.

The liver synthesizes complex protein-lipid molecules. They are of different composition and size. Hepatocytes produce two types:

  • high density lipoprotein (HDL);
  • very low density lipoproteins (VLDL)

Their balance, as well as cholesterol levels, determine the risk of developing atherosclerosis. Atherosclerotic plaques are formed with a decrease in VLDL, an increase in cholesterol and HDL.

Protein metabolism

Amino acids released from food proteins enter the liver through the portal vein. Their metabolic pathways are varied:

  • synthesis of your own proteins;
  • metabolism of nonessential amino acids by transamination ;
  • formation and neutralization of ammonia;
  • production of non-protein nitrogenous compounds (choline, nucleotides).

Hepatocytes synthesize 12 g of albumin per day, proteins of the immune system – globulins, coagulants – fibrinogen, prothrombin, proaccellin .

Ethanol metabolism

Alcohol from the stomach is quickly absorbed and goes to the liver for metabolism. Its disposal occurs in three ways with the formation of a toxic substance – acetaldehyde:

  1. Oxidation with alcohol dehydrogenase.
  2. Microsomal oxidation.
  3. Catalase way.

The first path is the most significant. Alcohol dehydrogenase hydrolyzes ethanol, but the reaction is reversible. The enzyme NAD + / NADH takes part in the reaction. If the former predominates, the reaction goes towards the formation of acetaldehyde, if the latter, ethanol is synthesized.

In mitochondria, the amount of hydrogenase is constant and does not depend on the dose of alcohol taken. With chronic abuse, an enzyme deficiency occurs, then metabolism is redirected along the microsomal pathway. The cytochrome P 450 system can utilize 50-70% of the supplied alcohol. The disadvantage is that the lipid peroxidation reaction is simultaneously triggered, which damages cell membranes. In parallel, protein synthesis and gluconeogenesis are inhibited. Unused lactate is released into the bloodstream and causes acidosis. Acetyl- CoA accumulates , the synthesis of ketone bodies is stimulated, and the utilization of fatty acids is inhibited. Fat is deposited in the liver.

The catalase pathway recycles 2% alcohol and is not as important as the other two. The positive side is that hydrogen peroxide is utilized during its reactions.

Drug metabolism

Medicines are xenobiotics for our body and are rendered harmless by the liver. The reactions take place in two stages.

The first phase reactions occur in the endoplasmic reticulum with the participation of cytochrome P 450. Neutralization occurs through oxidation, reduction or hydrolysis reactions. Substances pass into a water-soluble form.

Some drugs, as a result of biotransformation, acquire the necessary therapeutic effect, others become more toxic.

The second phase of detoxification is conjugation with glutathione. Xenobiotics lose their activity and are excreted in the urine.

A feature of the detoxification system is that the microsomal oxidation system can be induced or inhibited by certain drugs. Therefore, the instructions for many drugs indicate that they cannot be combined with certain substances that can activate the cytochrome system, which will lead to an acceleration of metabolism and neutralization of the drug. Or vice versa, negative manifestations and side effects may increase.

Hormone metabolism

The liver metabolizes biologically active substances. Peptide-based hormones, insulin and glucagon, are rendered harmless by nitrogen group removal or hydrolysis. Thyroid hormones lose iodine. Adrenal hormones and aldosterone undergo several complex reactions, the end result of which is conjugation with glucuronic acid. Testosterone is used to form androsterone and is excreted in the urine. Estrogen breaks down to estriol and estrone, which bind to sulfates or glucuronic acid and are excreted by the kidneys.

Liver damage alters the metabolism of all substances. Therefore, liver diseases are accompanied by hormonal disorders, a malfunction in the immune system, fat, carbohydrate metabolism.

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