CLASSIFICATION AND NOMENCLATURE OF ENZYMES

Modern classification and nomenclature of enzymes elaborated by the Commission on Enzymes of the International Union of Biochemistry and approved at the V International Congress of biochemistry in 1961 in Moscow.

The classification is based on three principles:

1. The chemical nature of the enzyme.

2. The chemical nature of the substrate.

3. Type of catalyzed reaction.

According to modern classification, the enzymes are divided into six major classes.

1. Oxidoreductases are enzymes that catalyze oxidation-reduction reactions:

                                   piruvate                             lactate

Aerobic dehydrogenase, or oxidase, catalyzes the transfer of protons (or electrons) directly to the oxygen.

Anaerobic dehydrogenase accelerates the transfer of protons (electrons) to an intermediate substrate, but not on oxygen.

The most common oxidoreductases contain as an active group nicotinamide adenine dinucleotide NAD⁺. Pyridine enzymes also contain as coenzyme nicotinamide adenine dinucleotide phosphate (NADP⁺). Coenzymes of oxidoreductases are also flavoproteins (FP) - flavin mononucleotide, FMN, and flavin adenine dinucleotide, FAD.

2. Transferases are enzymes that catalyze reactions of intermolecular transfer of various atoms and groups of atoms.

Phosphotransferases carry residue of phosphoric acid. Phosphate esters of organic compounds have increased chemical activity. ATP is a donor of phosphate group in most cases.

Aminotransferases accelerate reaction of amino group transport from the amino acids to α -keto acids.

 

Proteinase s accelerate the transfer of phosphate residue from ATP to proteins, altering their biological activity.

Glycosyl transferases accelerate transfer of glycosyl residues.

Acyltransferases catalyze the transfer of acyl groups (carboxylic acid residues).

3. Hydrolases catalyze splitting of the intramolecular bonds of organic compounds with the participation of water. They are named in the form of " substrate-hydrolase."

Esterase s catalyze the hydrolysis of the esters of alcohols with organic and inorganic acids. For example, lipase accelerates hydrolysis of triacylglycerols (fats):

Phosphatases catalyze the hydrolysis of phosphoric esters:

glucose-6-phosphate + H₂O ® glucose + H₃PO₄

Glycosidases catalyze the hydrolysis of glycosides. Amylases are the most famous of glycosidases, acting on polysaccharides.

Peptidhydrolases accelerate the hydrolysis of peptide bonds in proteins and peptides.

4. Lyases are enzymes that catalyze the breaking of the C-O, C-C, C-N and other bonds, as well as the reversible reaction of detachment of the different groups of substrates by non-hydrolytic way, or addition - elimination. These reactions are accompanied by the formation of the double bonds and the releasing of the simplest products, such as CO₂, H₂O, NH₃, and so on.

Carbon-carbon-lyase (decarboxylase):

5. Isomerases are enzymes that catalyze the interconversion of structural, optical and geometric isomers. Mutarotase accelerates the conversion reaction of α -D-glucopyranose in the β -D-glucopyranose:

6. Ligases (synthetases) are enzymes that catalyze the synthesis of organic compounds from two molecules with the decay energy of ATP or other substances.

One of the most important is the pyruvate carboxylase:

CH₃-CO-COOH + CO₂ ® HOOC-CH₂-CO-COOH

The International Commission has prepared Enzymes Classification (EC). Code of each enzyme contains four numbers separated by points. The first digit indicates the class number. The second digit indicates the subclass and characterized the type of substrate. For example, for transferases it indicates the nature of a transferred group, for the hydrolases it point to the type of hydrolyzed bond. The third digit specifies the nature of compounds or groups participating in the reaction. The fourth digit is number of the enzyme in the sub subclass.

An example: Pepsin - peptide-peptide hydrolase, EC 3.4.4.1.

 

ENZYMES IN MEDICINE

Enzymes are used as therapeutic agents:

- in their absence or deficiency (inherited or acquired);

- for the specific destruction of some metabolic products.

Enzyme	The use of the enzyme
Pepsin	Disorders in digestion of proteins in the stomach
Urease	Removal of urea from the organism in the apparatus of " artificial kidney"
Hyaluronidase	Resorption of scars
Streptokinase, urokinase	Preventing blood clots formation during operations

 

Enzymes are used in the clinic as analytical reagents.

Immobilized enzymes are often used for the analysis, which are artificially connected with the water-insoluble carrier, which increases the stability of protein catalysts.

Enzyme	The use of enzyme
Glucose oxidase	Determination of glucose concentrations in blood
Lipase	Determination of triacylglycerols concentration in blood
Cholesterol oxidase	Determination of cholesterol in blood

 

Analysis of the kinetics of appearance and disappearance of enzymes in the serum is used in the diagnosis.

The composition of enzymes and their tissue distribution in an adult is mainly constant and can change in diseases. Almost all of the enzymes of the organism are functioning intracellularly. When tissue is damaged intracellular enzymes appear in the serum. Such enzymes are called indicator enzymes.

By the appearance of several tissue enzymes in plasma or serum in high amounts one can conclude on the functional status and lesions of various organs.

Disease	Enzyme
Myocardial infarction	Creatine kinase, aspartate transaminase, LDH-1
Viral hepatitis	Alanine transaminase, aspartate transaminase, glutamate dehydrogenase
Pancreatic diseases	a-amylase
Liver diseases	Alanine transaminase, g-glutamyltransferase

 

Enzimopathy (synonym fermentopathy ) is the common name of diseases, developing as a result of the absence or decreased activity of certain enzymes. As a result of the interdependence of metabolic pathways defect of a single enzyme often leads to a number of disorders in the metabolism.

We distinguish hereditary and acquired enzymopathy.

1. Hereditary enzimopathys are associated with genetically determined deficiency of one or more enzymes. There are more than 150 hereditary enzymopathies, which are based on gene mutations.

2. Acquired enzimopathy.

Toxic enzymopathy is a consequence of toxic effects of xenobiotics and environmental mutagens. Lead, which is contained in the transport exhaust fumes, causes a inhibition of the enzyme aminolevulinatdehydrase involved in the synthesis of heme, which manifests the development of anemia of children in the city.

Nutritional enzymopathy may be due to prolonged lack of protein in the diet, vitamin deficiency, unbalanced nutrition.

Test Questions

1. Describe the chemical nature and structure of enzymes.

2. What is the structure of the active center of enzyme? What is the allosteric center?

3. Give examples of isozymes; multimolecular enzyme systems.

4. On what basis enzymes are classified?

5. Describe the mechanism of enzyme action.

6. What is the difference between the theories of Fisher and Koshland?

7. How do changes in pH and temperature influence on the rate of enzymatic reactions?

8. What is meant by the specificity of enzyme action?

9. How is the regulation of enzyme activity done?

10. What types of enzymes inhibition do you know?

11. How can be carried out in practice the determination of the enzymes activity?

12. Give examples of the enzymes usage in medicine.

 

VITAMINS

Vitamins (from Lat. vita - life) are organic compounds required in the diet in small amounts. They ensure the normal development of human and animal, and an adequate rate of occurrence of biochemical and physiological processes.

Vitamins are the assembly group of organic compounds in the chemical and physical point of view. The physiological effects of vitamins are also very different.

100 years ago it was believed that for the normal life of the human organism flux of proteins, fats, carbohydrates, minerals and water is enough. Practice and experience have shown that there are specific diseases which development is directly related to malnutrition (scurvy, beriberi).

The need for vitamins is negligible: approximately a person should consume daily 0.1 - 0.2 g. of vitamins. In many cases, vitamins are components of enzymes.

Avitaminosis ( vitamin deficiency ) is a disease that occurs in the absence of food vitamins or in total violation of assimilation of any vitamin.

Hypovitaminosis is insufficient intake of vitamins with food or their incomplete assimilation.

Hypervitaminosis is pathological state associated with large quantities of vitamins in the organism.

The causes of hypo- and avitaminosis in humans and animals are usually divided into exogenous and endogenous. An exogenous factor is insufficient intake of vitamins or their complete absence in the diet. Endogenous factors are: a) increased requirement for vitamins in certain physiological and pathological conditions (pregnancy, hyperthyroidism); b) violation of the process of absorption of vitamins in the digestive tract diseases; c) enhanced disruption of vitamins in the intestine due to the development of its flora; d) liver, pancreas diseases, accompanied by malabsorption of fat and therefore fat-soluble vitamins.

The classification is currently used based on the solubility of the vitamins.

FAT SOLUBLE VITAMINS

Vitamin A ( retinol ). Vitamin A has several vitamers.

Vitamer is a substance similar in chemical structure and having physiological effects characteristic of a particular vitamin.

Retinol is oxidized in the organism with the participation of the biocatalyst. It is converted to retinal, also having the activity of vitamin A.

Vitamin A affects the barrier function of skin, mucous membranes, the permeability of cell membranes and biosynthesis of glycoproteins, it is involved in light perception, being a part of the photosensitive pigment rhodopsin.

Vitamin A deficiency leads to inhibition of growth, weight loss, lesions of skin, mucous membranes and eyes (night blindness).

Vitamin A is found in liver, egg yolk, milk, oil; provitamin A (carotene) - in red pulp vegetables. Daily requirement is 2.7 mg. In humans body vitamin A is stored mostly in liver.

There are cases of A hypervitaminosis at eating polar bear, seal, walrus liver, which contains plenty of vitamin A. Hypervitaminosis may develop as a result of receiving large amounts of fish oil and preparations with vitamin A. The characteristics of hypervitaminosis are eye inflammation, hair loss, headaches, dyspepsia (nausea, vomiting) dermatitis.

Vitamin D (calciferol) in the human organism exists as a form of D₂ and D₃. Precursor of vitamin D₂ (ergocalciferol) is ergosterol, which is present in plants. Precursor of vitamin D₃ (cholecalciferol) is cholesterol, which is present in animals. Ergosterol and cholesterol are transformed into D₂ and D₃ under the influence of solar radiation.

Calciferols are involved in the regulation of calcium and phosphorus digestion in the intestine, in osteogenesis, in the synthesis of mRNA and Ca-binding proteins and hormones.

Vitamin D deficiency in children leads to rickets. The result is bone softening and deformation, thickening at the bone-cartilage boundary ribs, large head, enlarged abdomen due to the muscle hypotonia). D avitaminosis in adults leads to osteomalacia and osteoporosis. It is bone demineralisation, causing the bones become fragile.

D hypervitaminosis is observed at very high dosages of vitamin and can be fatal. Toxic effect includes resorption of bones and deposition of phosphates in soft tissues (kidney and arteries).

Vitamin D is found in animal products - butter, liver, egg yolk and oil. Daily requirement is 10 micrograms, for children - 20-25 microgramms. To prevent rickets in children UV irradiation is recommended.

Vitamin E (tocopherol) (from the Greek Tokos - descendants, Fero - bring) got its name because it was established that it regulates the process of reproduction in rats.

Vitamin E is one of the strongest natural antioxidants. It protects polyunsaturated fatty acids and lipids of cell membranes from oxidation, especially from peroxidation reactions.

In the absence or deficiency of vitamin E in humans and animals embryogenesis is disturbed and degenerative changes in the reproductive organs are observed. Degeneration of the spinal cord develops and there is paralysis of limbs, fatty liver, muscular dystrophy, biochemical changes in muscles.

Sources of Vitamin E are mainly vegetable oils, cabbage and grain products. It also contained in meat, milk, butter, eggs. Vitamin E is deposited in muscle, pancreas, so the development of avitaminosis is almost not observed. Daily requirement is 5 milligrams.

Vitamin K (phyllochinone). It regulates the process of blood clotting. Vitamin K deficiency can lead to spontaneous nosebleeds, bloody vomiting and internal bleeding. K avitaminosis is rare. A mixed diet is rich enough with it; the intestinal micro flora is capable of synthesizing vitamin K.

The drug " vikasol" is derived from vitamin К ₃.

WATER SOLUBLE VITAMINS

Vitamin C (ascorbic acid) is colorless crystals with acidic taste.

Ascorbic acid participates in the redox processes. It is involved in the synthesis of collagen, folic acid, adrenal hormones, and tryptophan. It is important in the breakdown of hemoglobin in tissues. Vitamin C enhances the synthesis of immunoglobulins.

Deficiency of vitamin C leads to lessening of organism weight, weakness, shortness of breath, heart pain, decreasing of immunocompetence. In severe cases scurvy develops. The permeability and fragility of blood vessels increase. There are spontaneous hemorrhages, and loss of teeth. The basis for these phenomena is disorders of collagen synthesis.

Source of vitamin C for humans are canker berry, black currants, mountain ash, red pepper, tomatoes, lemons, and cabbage. Daily requirement is 75 mg.

Vitamin B₁ (thiamine) is the first crystalline vitamin produced in the laboratory. It contains pyrimidine and thiazole rings having a methylene bridge.

The active form of thiamine is thiamine pyrophosphate (TPP, or cocarboxylase). It is part of the five enzymes involved in intermediate metabolism. Usually it is decarboxylation reactions. TPP is connected with energy releasing reactions.

Symptoms of avitaminosis В₁ are disruption of the digestive system, mental disorders (hallucinations), degenerative changes in nerve endings and the vascular bundles, atrophy and paralysis of limbs, depression of the cardiovascular system. The В₁-avitaminosis results in disease called (" beri-beri" polyneuritis), which can lead to paralysis and death.

Sources of vitamin В₁ are yeast, cereals, nuts, bread from meal, when the grain during processing does not lose the embryos and membranes. In animal products it is found in the liver, kidneys and brain. Daily requirement is 1.2 mg.

Vitamin B₂ (riboflavin). The basis of the riboflavin molecule is isoalloxazine, which combines benzene, pyrazine and pyrimidine rings. It is a substance of yellow color.

The ability of riboflavin to be easily oxidized and restored is the basis of its biological effects. Riboflavin is a coenzyme of oxidoreductases (part of the FAD and FMN).

Riboflavin deficiency lead to the stop of hair growth, loss of hair, dermatitis, mucous membranes damage (especially in the corners of the mouth), fatigability, decrease in working capacity, disruption of normal hemoglobin synthesis; muscular weakness.

Sources of vitamin В₂ are milk, meat, liver, kidney, eggs, yeast, green vegetables, cereals, fruits. Daily requirement is 1.7 mg.

Vitamin В ₆ (pyridoxine) is a derivative of 3-oxypyridine. It presents itself with pyridoxole, pyridoxal and pyridoxamine, all of them in the organism are able to transform to the pyridoxal phosphate, which participates in chemical reactions.

Pyridoxal phosphate is the prosthetic group of carboxylases and transaminases involved in the formation of biogenic amines, transformation of amino acids, and synthesis of heme of hemoglobin.

В₆ deficiency disease involves violations of the metabolism of proteins and amino acids. The main symptoms are a violation of hematopoiesis and the development of various types of dermatitis that cannot undergo the treatment with nicotinic acid. В₆-vitamin deficiency is also accompanied by violation of lipid metabolism that leads to the development of atherosclerosis.

Sources of pyridoxine are beef, fish, peas, egg yolk and green parts of plants. Daily requirement is 2 mg. Since vitamin B₆ is widely distributed in foods and can be partially synthesized by intestinal micro flora, in normal conditions, B₆-deficiency disease in humans has not been observed.

Vitamin B₁₂ (cobalamin). It contains the grouping of four pyrrol rings with Co atom in the center.

Derivatives of B₁₂ coenzymes are composed of a number of enzymes that accelerate the most important reactions of nitrogen-containing compounds, carbohydrate, nucleic acid and lipid metabolism. B₁₂ is involved in transmethylation reactions, intramolecular transfer of H atoms and various functional groups (hydroxyl, amine, etc.).

With a lack of vitamin B₁₂ disruption of hematopoiesis in bone marrow occurs, causing anemia malignant megablastic, disruption of the nervous system, reducing the acidity of gastric juice.

Vitamin B₁₂ is the only vitamin the synthesis of which is carried out only by microorganisms. Sources of cobalamin: meat, beef liver, fish, milk and eggs. Plants do not contain vitamin B₁₂. Depot of vitamin B₁₂ in humans is in the liver, where it accumulates in the amount of a few milligrams. Daily requirement is 3 micrograms.

Vitamin B₅ (pantothenic acid) is found in all animal, plant and microbial objects (Greek pantos - everywhere).

Pantothenic acid is a part of coenzyme A. CoA is involved in transfer reactions of acyl groups. A number of biochemical reactions are associated with CoA that underlies the oxidation and fatty acid synthesis, the biosynthesis of fats, oxidation of breaking up products of carbohydrates.

In the absence of vitamin B₅ there can be dermatitis, slow growth, there is weight loss, hair loss and depigmentation of hair, degenerative changes in the nervous system. Discoordination of movements, paralysis, disruption of the gastrointestinal tract, reproductive organs and adrenal glands can be related to this.

In humans, B₅ vitamin deficiency is rare as pantothenic acid is produced by intestinal micro flora. Sources are yeast, milk, eggs, liver, kidneys, peas, cauliflower, potatoes, tomatoes. Daily requirement is 10 mg.

Vitamin PP (nicotinic acid and nicotinamide, niacin, B₃) is a derivative of pyridine. Vitamin PP is involved in all types of metabolism: carbohydrate, protein and lipid. Nicotinamide is a part of the most important coenzymes – NAD⁺ (nicotinamide adenine dinucleotide) and NADP⁺ (nicotinamide adenine dinucleotide phosphate), involved in redox reactions. Vitamin PP is necessary for energy production.

Avitaminosis PP is expressed in an inflammation of the mucous membranes of the gastrointestinal tract, and then a skin inflammation (dermatitis) on the areas which are exposed to the sun irradiation. It is a pellagra disease. Also damage of the brain is observed. So, it is a disease of 3D: dermatitis, diarrhea, dementia.

Sources of vitamin PP for humans are liver and kidneys of animals, yeast, buckwheat, beans, etc. A certain amount of nicotinic acid is synthesized in the human organism from the amino acid tryptophan. Daily requirement is 18 mg.

Folic acid, vitamin В_с (pteroylglutamic acid).

В_с vitamin deficiency is rare, because folic acid is synthesized by the micro flora of the gastrointestinal tract and always enters the organism in sufficient quantity, but in the case of this vitamin deficiency anemia and disorders of the digestive organs can occur.

Folic acid, as a coenzyme of several enzymes, carries one-carbon fragments in the biosynthesis of many compounds: methyl group, oximethyl (-СН₂ОН), formyl.

Sources of folic acid are spinach, cauliflower, animal’s liver, bread. Particularly high content of it is in yeast.

Vitamin P (rutin). Currently, there are many compounds with P-vitamin activity. They are called bioflavonoids.

In the absence of vitamin P capillary permeability is increased, which is accompanied by bleeding, pain in the limbs, general weakness and fatigue. It is suggested that vitamins P are involved in redox reactions.

Source of vitamin P for a human are the same products, in which there are a lot of vitamin C, such as black currant and lemon.

Vitamin H (biotin). With a lack of this vitamin in humans there is inflammation of the skin, hair loss, increased allocation of fat by sebaceous glands of the skin (seborrhea). The mechanism of biotin action: as a coenzyme it is part of enzymes that increased the velocity of carboxylation reactions.

Source of vitamin H are the liver and kidneys of cattle, eggs, milk, tomatoes, soybeans, carrots, potatoes, peas. The intake of biotin in the organism is also possible from microbial symbionts.

Vitamin-like substances

In addition to the two main groups of vitamins, we distinguish group of chemicals, part of which is synthesized in the organism, but it has vitamin properties. These include choline, lipoic acid, vitamin В₁₅, para-aminobenzoic acid, carnitine, linoleic and linolenic acid, vitamin U, inositol and others.

Antivitamins are compound similar in structure to vitamins, which compete with vitamins in the relevant biochemical processes or switch-off vitamins of the metabolic processes by means of their destruction or binding.

An example of competing antivitamins is structural analogues of vitamin PP. They are able to form pseudo-coenzymes which simulate NAD⁺ and block the activity of NAD⁺-dependent oxidoreductases.

An example of switch-off antivitamins is avidin – the protein of egg white, which forms insoluble biologically inactive complex with vitamin H.

Since bacteria and viruses, as well as tumor cells have increased sensitivity to the lack of some vitamins, antivitamins are used as therapeutic agents.

Test Questions

1. Give known classifications of vitamins.

2. Describe the biological role of vitamins.

3. Give the definitions of avitaminosis, hypovitaminosis, hypervitaminosis.

4. What are the causes of avitaminosis and hypovitaminosis of the human organism?

5. What substances are called antivitamins? How do they work?

6. List fat-soluble vitamins. Describe their biochemical functions.

7. List water-soluble vitamins. Derivatives of what vitamins are coenzymes, transferring methyl and amino groups?

8. Explain why the sulfonamide drugs cause death of the bacteria and can be used as medicine?

9. What vitamins can be used in the treatment of skin diseases?

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