LACTATE DEHYDROGENASE

From Big Medical Encyclopedia

LACTATE DEHYDROGENASE (L-lactate: OVER — oxidoreductase; KF 1.1.1.27 and 28; LDG) - the enzyme of carbohydrate metabolism catalyzing one of the most important reactions of anaerobic glycolysis — interconversion pyroracemic and milk to - t.

Activity of this enzyme in blood serum and abundance of its isoenzymes are important biochemical diagnostic test at a number of diseases.

The lactate dehydrogenase is found in all tissues of animals and the person, especially in cordial and skeletal muscles, erythrocytes, a liver and kidneys. It is localized by L. in cytoplasm.

In physiological conditions balance of the reaction catalyzed by L., it is displaced towards education milk to - you (lactate). Coenzyme of L. is OVER (see, Nicotinamide adenine dinucleotide ).

Recovery of pyruvate under the influence of L. completes an internal oxidation-reduction cycle glycolysis (see). When cells of muscles of the higher organisms in the conditions of a big muscular exercise are forced to function in anaerobic conditions, from muscles a large number of a lactate comes to blood. In a liver this lactate turns again in glucose (see). The exhaustion of muscles is partially caused by development of acidosis in muscles since at glycolysis two molecules milk to - you (are formed of each neutral molecule of glucose see. Lactacidemia ).

From the point of view of kinetics, the reactions catalyzed by L., represent two-substrate reactions with the arranged binding of substrates. The first with L. the coenzyme communicates, reaction products dissociate consistently. In reaction of recovery of pyruvate the stage limiting speed of response is the isomerization of a triple complex: L. — NAD-N — pyruvate. In oxidation reaction of a lactate such limiting stage is dissociation of pyruvate or NAD-N2. In addition to pyruvate, L. catalyzes recovery homologous to it alpha ketonic acids — alpha-oxobutyric, alpha and ketovalerian and alpha and ketokapron. L. it is inactive during the use as substrates oxalacetic (oxalate) and alpha and keto-glutaric to - t, and also beta and δ-ketonic acids, ketones and acetic aldehyde. L. has strict stereospecificity: it catalyzes oxidation only L-milk to - you; at recovery optically of inactive pyruvate only L-milk to - that is also formed (see. Isomerism ).

Activity of L. usually determine by the spectrophotometric method based on measurement of absorption of NAD-N 2 at 340 nanometers.

Amino-acid structure and primary structure of L. differ depending on a source of release of enzyme and its isofermental structure (see. Isoenzymes ). Pier. weight (weight) of L. about 140 000 is equal. Molecule L. represents the tetramer consisting of one or two types of subunits. In each of them there are remains of cysteine and a histidine essential to manifestation of enzymatic activity which blocking leads to an inactivation of enzyme. An active center in a molecule L., where there is a binding of a coenzyme and substrate, represents the hydrophobic area 1,4 nanometers long containing the remains of arginine, dicarbonic to - t and a histidine.

The lactate and pyruvate in high concentration cause inhibition of L. owing to formation of unproductive complexes with enzyme.

Adeninovy nucleotides, oxalate and an oxamat reversibly and competitively inhibit L. Dezamino-NAD effectively participates in the reaction catalyzed by L.

L. exists at least in five various molecular forms, i.e. enzyme is presented by five isoenzymes which designate as an arrangement them on an elektroforegramma towards the anode at alkaline pH values: LDG1, LDG2, LDG3, LDG4 and LDG5. The cardiac muscle and kidneys contains hl. obr. LDG1. In skeletal muscles and in a liver contains in the main LDG5. Catalyzing the same reaction, isoenzymes of L. accurately differ in sizes of constants of Mikhaelis — Menthene (Km) for substrates. It was suggested that separate isoenzymes preferably catalyze forward or back laktatdegidrogenazny reaction.

Polypeptide chains in molecules of isoenzymes of L. can be two various types designated usually by M or N. Ustanovleno that five isoenzymes of L. have the following subunit composition: LDG1 — H4, LDG2-N3M, LDG3-N2M2, LDG4 — H1M3 and LDG5 — M4. Isoenzymes of L. the M4 and HM3 type contain preferential in those fabrics in which energy is formed due to glycolysis, napr, in white skeletal muscles or in embryonal fabrics. Isoenzymes like H3M and H4 meet hl. obr. in fabrics of which aerobic or respiratory metabolism is characteristic. Isoenzymes of L. differ from each other in ability to an inactivation in high concentration of pyruvate. The isoenzyme of LDG5 is more sensitive in relation to pyruvate that is explained by the most high speed of formation of a triple unproductive complex L by it. — NAD-N — pyruvate and its stability. In an organism subunits of L are usually synthesized. both types, but in unequal quantity for different fabrics that causes assembly of these or those isoenzymes of L., specific to this or that fabric. Peptide chains of two types of subunits of L. are coded by two different genes. Influence of mutations on izofermeita of L. depends on whether there are they in the locus coding biosynthesis of a chain of M or in the locus defining biosynthesis of a chain N. Tak, the mutation in M.'s locus does not influence LDG1 properties as this isoenzyme does not contain subunits of M. At the same time such mutation in different degree changes LDG2, LDG3, LDG4 and LDG5 properties, subunits of M containing corresponding quantity. Similar to a mutation in a locus In shall not mention LDG5, unlike other four isoenzymes

of L. U of heterozygotes (see. Mendel laws ) very difficult enrollment of isoenzymes L. Tak, at an individual, heterozygous on M.'s locus, but a locus of N, homozygous on a normal allele, is synthesized, 15 isoenzymes of L can be synthesized., which distribution will be other, than at an individual, heterozygous on a locus of N, but homozygous is determined by M. Sootnosheniye's locus of normal and alternative isoenzymes by a ratio of the normal and alternative polypeptides available to formation of tetramers.

At people the considerable number of options L is found., differing on the isofermental range (qualitatively and quantitatively). All of them are rather rare and were found by an ordinary electrophoretic research. Any of the known options, apparently, is not connected with any defined clinically shown anomaly. In each case difficult, but absolutely certain picture of electrophoretic division is observed.

Except the loci coding M - and N-subunits of L., there is, apparently, a third locus defining one more subunit. Existence of this subunit leads to emergence of special type of a tetrameric isoenzyme (the strip corresponding to it on an elektroforegramma call the H-strip), the person, characteristic of spermatozoa, and animals.

Clinical value of definition of activity of a lactate dehydrogenase

in several hours after the beginning of an acute myocardial infarction in blood serum note substantial increase of activity of L. In 36 — 48 hours this activity reaches the maximum (quite often it by 10 — 15 times exceeds normal). The optimum period for definition of activity of L. in blood serum makes 2 — 4 days after the beginning of a heart attack since in this time span the value of this biochemical, the test is most big. So, e.g., its diagnostic accuracy, by data I. V. Martynova, at a transmural myocardial infarction in this interval of time is equal 97 ± 1,7%.

Usually activity of L. in blood serum at a heart attack is returned to norm on 10 — the 12th day later began diseases. Activity of L. in blood serum at a myocardial infarction remains raised longer than other enzymes (e.g., aminotransferases).

Value of definition of activity of L. in blood serum it is especially big in not clear cases of a myocardial infarction (at atypical a wedge, and electrocardiographic pictures, in particular at the long anginous attacks which are followed by passing deformation of a S T segment or tooth of T without emergence patol, a tooth of Q), and also for differential diagnosis between a myocardial infarction and the stratifying aortic aneurysm, an acute pericardis and thrombosis of a pulmonary artery. At all these diseases increase in activity of L. in blood serum not so sharp, as at a myocardial infarction.

However size of activity of L. does not allow to judge with confidence the amount of damage of a cardiac muscle and the more so to predict an outcome of a disease.

At patients with stenocardia of increase in activity of L. in blood serum it is not observed. It allows to apply the LDG-test as reliable criterion of lack of damage of a cardiac muscle within 2 — 3 days after heart attack.

Activity of L. in blood serum raises at parenchymatous hepatitis in the first days of the icteric period. At an easy and medium-weight form of a disease activity of enzyme quickly enough is returned to norm. At mechanical jaundice activity of L. in blood serum remains normal, only at late stages of a disease it raises owing to secondary damages of a parenchyma of a liver. At carcinomas of a liver and metastasises of cancer in a liver activity of L. in blood serum can also increase; at the same time concentration of pyruvate in blood serum increases by 2 — 3 times (norm of 0,5 — 1,0 mg of %). However the negative take of the LDG-test in this case does not testify to lack of malignant damage of a liver at all.

In a stage of remission hron, hepatitis activity of L. in blood serum remains within norm or slightly raises, at an aggravation of process increases. In this case the LDG-test can be used as auxiliary together with other fermental tests.

Activity of L. in blood serum increases also at the progressing muscular dystrophy, hron, a lymphogranulomatosis, leukoses, pernicious anemia, acute and hron, nephrites, at tumors in urinary tract and other diseases.

More importance in diagnosis in comparison with definition of the general activity serumal L. has definition of isofermental list of L. Obychno in blood serum of healthy people all 5 fractions L are found., which activity is distributed as follows: >>>>LDG2LDG1LDG3LDG4LDG5. At an acute myocardial infarction the ratio between activities of LDG1 and LDG2 so changes that activity of LDG1 becomes equal activity of LDG2 or above it. This indicator is of great importance in late diagnosis of a myocardial infarction. Besides owing to specificity of this test it can be used for differential diagnosis.

At parenchymatous damages of tissue of liver (infectious hepatitis), and also at some diseases of muscles (the progressing muscular dystrophy) find substantial increase of abundance of LDG5 that also finds application in an enzimodiagnostika of these diseases.

See also Dehydrogenases .



Bibliography: Nyoskholm E. and Start To. Regulation of metabolism, the lane with English, page 111, 291, M., 1977; With e in e r and S. E's N. Glycolysis, in book: Chemical bases of processes shiznedeit., under the editorship of V. N. Orekhovich, page 156, M., 1962; Harris G. Fundamentals of biochemical genetics of the person, the lane with English, page 53, M., 1973; Holbro ok J. J. and. the lake of Lactate dehydrogenase, in book: Enzymes, ed. by P. D. Boyer, v. And, p. 191, N. Y. — L., 1975, bibliogr.


G. Ya. Vidershayn.

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