From Big Medical Encyclopedia

PORPHYRINES — pigments, eurysynusic in the nature, the representing derivatives of porphin and the performing important functions in processes of life activity of animals and plants. Items are molecular composition respiratory pigments (see), including. hemoglobin (see) and myoglobin (see), various enzymes (see), chlorophyll (see) and t. l.

And their chemical structures were devoted to P.'s studying M. V. Nentsky, I. A. Zalessky, L. A. Markhlevsky's many works. The significant contribution to development of methods of synthesis, the analysis and P.'s definition made Fischer (N. Fischer), R. Woodward, R. P. Yevstigneyeva, etc.

In a stand-at-ease and in a complex meet proteins P. in a human body and animals, in plants, in microorganisms. Find P. in oil, bitumakht asphalt, voska, black coal.

The basis of a molecule P. is made by the ring of porphin constructed of four pyrrol kernels, and - carbon atoms to-rykh metinovy bridges (= With —) are connected with each other, and R-hydrogen atoms are replaced by various hydrocarbon radicals, the nature to-rykh and the relative arrangement, and also presence of atom of metal, etc. define P.'s difference from each other.

R1 — R8 — hydrocarbon radicals; R1=R2 =... R8=H — porphyrine; R1=R3=R5=R7=CH2COOH, R2=R4=R6=R8=C2H4COOH — uroporfirin I;

R1=R3=R5=R8=CH2COOH, R2=R4=R6=R7=C2H4COOH - uroporfirin III;

R1=R3=R5 — R8 — CH3, R2=R4=CH=CH2, R6=R7=C2H4COOH — protoporphyrin IX;

R1=R3=R5=R7=CH3, R2=R4=R6=R8=CH2CH3 — etioporfirin I;

R1=R3=R3=R8=CH3, R2=R4=R6=R7=CH2CH3 — etioporfirin III;

R1=R3=R5=R7=CH3, R2=R4=R6=R8=C2H4COOH — coproporphyrin I;

R1=R3=R5=R8=CH3, R2=R4=R6=R7=C2H4COOH — coproporphyrin III.

The items supporting identical number of deputies of two types (etioporfirina, coproporphyrins, uroporfirina), depending on an arrangement of side chains of rather porphyrinic kernel can exist in 4 isomeric forms, and P., the containing deputies of three types (meso - and protoporphyrins), can exist in 15 isomeric forms.

Items represent amphoteric connections with an isoelectric point at pH apprx. 4,0, easily forming complexes with metals which also have intensive coloring.

Depending on the nature of deputies of P. are dissolved in alkaline solutions and mineral to-takh, ether, pyridine. P.'s ability to be distributed between ether and solutions salt to - you have practical value for unmixing of P. and their individual characteristic. Concentration salt to - you as a percentage, at a cut after establishment of balance two thirds of P. are in a radio phase of the two-phase system consisting of equal volumes of ether and solution salt to - you, call muriatic number of porphyrines. The muriatic number for coproporphyrin makes 0,08, for protoporphyrin — apprx. 2,5.

Items possess characteristic absorption spectrums: situation and intensity of maxima of absorption are defined by electronic transitions in a porphyrinic macrocycle. For P. the most intensive strip of absorption in the area apprx. 400 nanometers is inherent (a strip Soar); Items, free of metal, in neutral and acid solutions are characterized by intensive red fluorescence, the range a cut depends on the size pH of solution. P.'s fluorescence has important biological value and also is used at

P. V identification molecules of complexes P. with metals the ion of metal is in the center of a porphyrinic ring, and 4 ligandny places of metal are taken by nitrogen atoms of pirrol. The most important metalloporfirino-vy complexes are: in an organism of animals and the person — the complex of protoporphyrin IX with bivalent iron (gems) which is a part of hemoglobin and a myoglobin, and also complexes P. with iron in molecular composition tsitokhrom (see), catalases (see), peroxidases (see); at plants — complexes P. with magnesium in molecular composition of a chlorophyll (di - and tetragidromagniyporfirina). Functional metal of otetrapirrol biogenic is close to representatives also B12 vitamin (see. Cyanocobalamine ). Complexes P. with vanadium, zinc, copper are described. In breath of animal organisms, in photosynthesis at plants and in azotfixation at microorganisms metalloporphyrins take part in a type of proteinaceous complexes.

Metalloporphyrins show catalytic activity also in the form of complexes with proteins.

The free P. which are not a part of fermental or pigmental complexes are found in organisms of many representatives of an animal and flora. Some microorganisms are capable to accumulate P. in the course of the life activity. Items are found in covers of sea hedgehogs and stars, a shell of eggs of nek-ry birds, in garderovy glands of rodents. In a human body the major representative P. is protoporphyry in IX — the predecessor gem of hemoglobin, there are uroporfirina of I and III, coproporphyrins I and III, a mesotime-firin of IX and deuteroporphyrin IX. The free P. found in a human body in insignificant quantities are hl. obr. products of synthesis gem and almost completely communicate specific proteins of an organism. So, the R-glycoprotein of blood serum — hemopexin specifically connects gems.

In the bones which are especially quickly growing with active process of calcification, and also in marrow the quantity of free uroporfirin and coproporphyrins is revealed a nek-swarm. Endogenous P. are found in white matter of a head and spinal cord. Free P. are defined in an amniotic fluid, blood serum of embryos, meconium. On a nek-eye to data, in embryonal and tumoral fabrics there is P. V accumulation erythrocytes are found protoporphyry in (10 — 50 mkg on 100 ml of a suspension of cells), uroporfirin (to 4 mkg on 100 ml of a suspension of cells) and coproporphyrin (to 5 mkg on 100 ml of a suspension of cells). Blood serum also contains a small amount of the Item. Leukocytes normal do not contain P., but at nek-ry diseases are capable to synthesize them. The liver contains protoporphyry in IX, and also a set of the enzymes participating in synthesis of the Item. As a part of bile in 24 hours 280 — 600 mkg of porphyrines cosecrete. Per day about 500 mkg of porphyrines are brought out of an organism of the healthy person. Coproporphyrins I and III are emitted with urine (30 — 80 mkg! dry) and stake (100 — 400 mkg/days). Normal the size of a ratio of coproporphyrins in urine and in Calais makes 0,1 — 0,6, and at the diseases connected with pathology of porphyrinic exchange, this indicator raises. With urine in days 5 — 20 mkg of an uroporfirin of I and III are allocated. In urine find also colourless porphyrias of an ogena — got into condition by the Item. The quantity and character of the excreted P. are influenced by a diet. Fats and alcohol increase the level of removal of the Item.

Considerable part P. in a human body has an exogenous origin and gets to an organism with food. From P.'s intestines of food, the turning hl. obr. in coproporphyrin, come with a blood flow to a liver, from there as a part of bile get into intestines again, and then are brought out of an organism with a stake or in a small amount pass into blood and are allocated with urine. In P.'s intestines can be formed as a result of action of microorganisms of intestinal microflora on gemsoderzhashchy components of food, and also as a result of microbic synthesis of simple metabolites. P.'s education happens in a small bowel and an upper third of a large intestine. Thus, P. a calla have both exogenous (alimentary), and an endogenous origin.

In biosynthesis of porphyrines, the occurring hl. obr. in the hemopoietic bodies and a liver, the system of enzymes of various intracellular localization takes part. At the first stage of biosynthesis of porphyrines there is a formation of primary pirrol of porphobilinogen. Under the influence of enzyme of synthase 6-aminolevulinic to - you are carried out (KF reaction of interaction of amino acid of glycine with an active form amber to - you — suktsinil-KOA. At the same time CO2 and 6-aminolevulinic to - that is formed, two molecules a cut in the presence of specific aminolevulinat-dehydratase (KF are condensed with formation of porphobilinogen. At the second stage of biosynthesis of P. primary tetrapyrrole connections — porfirino-tena are formed. This process happens under action uroporphyrinogen 1-син-basins (KF, catalyzing formation of uroporphyrinogen I, and Sh-kosintazy uroporphyrinogen, promoting formation of uroporphyrinogen III. At the third stage decarboxylation of the remains acetic is carried out to - you in molecules of uroporphyrinogens I and III with education koproporfirinoge-are new I and III respectively. At presence koproporfirinogen-dekar-boksilazy the remains propionic to - you in a molecule of a koproporfirinogen III are decarboxylized and is formed protoporfirinogen by IX which then is oxidized to protoporphyrin IX. Further transformations are connected with education gem at the inclusion of iron in protoporphyrin IX catalyzed a hematin — ferroliazy (KF At an erythrocytolysis of P. gem are not used for its resynthesis, and break up with formation of tetrapirrol with an open chain — bilious pigments (see). Initial and final stages of biosynthesis of P. (education δ-aminolevulinic to - you to - you to - you, protoporphyrin IX and gem) prorshkhodit in mitochondrions, and other reactions (formation of uroporphyrinogen, a koproporfirinogen, uroporfirin and coproporphyrin) — in cytosol.

Regulation of biosynthesis of P. is carried out at various levels. Quantity 6-aminolevulinic to - you are regulated by the principle of a feed-back by an end product — gemy. Hormonal regulation of synthesis of P. can be both direct, and mediated (at the genetic level). It is established that in P.'s exchange a part is played by a hypophysis, especially a neurohypophysis. Also nervno-reflek-even mechanism of control of synthesis of the Item is revealed. Vitamins (B2, B12, C, pantothenic and folic to - you) clear relationship between proteinaceous and lipidic and mineral exchanges and exchange of the Item exerts impact on P. Proslezhivayutsya's exchange. Considerable stimulation of synthesis of porphyrines is caused by blood loss.

In an organism of the healthy person intermediate products of synthesis of P. contain in small amounts. A wedge, forms of disturbance of exchange of P. — porphyrias (see) — are followed by change of maintenance of P. in fabrics and increase in excretion free P. Geneticheski the caused porphyrias are characterized with biochemical, the points of view insufficiency of the enzyme catalyzing one of exchange reactions of the Item. Determination of content of P. in blood and urine and activity of enzymes of exchange of P. is reliable diagnostic test at porphyrias. Disturbance of exchange of P. and a purpurinuria are observed at diseases of a liver (e.g., cirrhosis), nek-ry poisonings (including at lead poisoning), and also at patients with malignant tumors.

The natural and synthetic P. entered into an organism are capable to be localized selectively in fabrics of malignant tumors and other proliferating fabrics and to change their radio sensitivity. Radio protective (radioprotek-even) properties of nek-ry P. (including an etioporfirina) are shown experimentally. Believe that radio protective action of P. is connected with their participation in metabolic processes in a cell. At radiation therapy of P. render exponential effect.

P.'s definition is made flyuorometrichesky and spectrophotometric methods, and P.'s division — extraction diethyl by ether from acid solutions and hromatografichesky division of extract on paper or by means of columnar and thin layer chromatography (see), and also method electrophoresis (see). High-quality detection of porphobilinogen in urine is based on its reaction with Ehrlich's reactant. In a lab. to practice semi-quantitative methods of definition of coproporphyrin on intensity of red fluorescence in UV rays are used. One of the most widespread is the determination of content of coproporphyrin in urine by Kaskelo's method based on P.'s ability to be extracted by diethyl ether from the solutions acidified acetic to - that, and from ether — water solutions salt to - you. Calculation of content of coproporphyrin perform on the basis of results measurements of optical density of solutions at 380 and 430 nanometers. Content of protoporphyrin in erythrocytes is determined by Grinstein and Uintrobu of a spektrofotometricheska after extraction of protoporphyrin consecutive by ethyl acetate and salt to - that.

See also Pigments .

Bibliography: Biochemical methods of a research in clinic, under the editorship of A. A. Pokrovsky, M., 1989; B y x about in with to and y V. Ya. Biogenez of tetrapyrrole connections (porphyrines and korrinoid) and his regulation, M., 1979; Guliyeva S.A. and Kubatiyev A. A. Rak and porphyrines, Vopr, onkol., t. 17, Jsfi 7, page 86, 1971; Kubatiyev A. A. Porphyrines, B12 vitamin and cancer, Tula, 1973; The biological role of porphyrins and related structures, ed. by A. D. Adler, N. Y., 1975; Fischer H. u. a. Die Chemie des Pyrrols, Bd 1 — 2, Lpz., 1934 — 1940; Goldberg A. Rimington C1.Diseases of porphyrin metabolism, Springfield, 1962; International conference on porphyrin metabolism, Biochemical and clinical aspects, ed. by P. Koskelo a. R. Tenhunen, Helsinki, 1976.

H, V. Gulyaeva.