Lactate dehydrogenase (LDH) is an enzyme that, through hydrogen transfer, catalyzes the oxidation of L-lactate to pyruvate with the mediation of NAD+ as a hydrogen acceptor. The enzyme has a molecular weight of 134 kDa and is composed of four peptide chains of two types (M and H), each under separate genetic control. The structures of LDH-M and LDH-H are expressed, respectively, from loci localized on chromosomes 11 and 12. The subunit compositions of the five isoenzymes, in descending order of anodic mobility in an alkaline medium, are: LDH-1 (HHHH; H4), LDH-2 (HHHM; H3M), LDH-3 (HHMM; H2M2), LDH-4 (HMMM; HM3), and LDH-5 (MMMM; M4). A sixth different isoenzyme of LDH, LDH-X, composed of 4 X subunits, is present in postpubertal human testes. A seventh LDH, termed LDH-6, has been identified in the sera of critically ill patients.

LDH activity is present in many human cells and tissues. The concentration of enzymes in tissues ranges from 1500 to 5000 times that found physiologically in serum. Thus, the release of the enzyme from even a small amount of damaged tissue significantly increases the observed serum LDH activity. Different tissues show different isoenzyme compositions. In the heart, kidney, and erythrocytes, LDH-1 and LDH-2 isoenzymes predominate, while LDH-4 and LDH-5 isoenzymes predominate in the liver and skeletal muscle.

Clinical Significance

Because of its wide tissue distribution, increases in serum LDH occur in a variety of clinical conditions, including myocardial infarction, hepatitis, and hemolysis. However, the measurement of LDH in the serum is relevant only in hematology and oncology.

Hemolytic anemia significantly increases serum LDH concentrations. Marked increases in LDH activity, up to 50 times the URL, are observed in megaloblastic anemias. The latter usually result from a deficiency of folic acid or vita min B12 and causes the weakening of the erythrocyte pre cursor cell in the bone marrow (ineffective erythropoiesis), leading to the release of large amounts of LDH. These increases quickly return to baseline values after appropriate treatment.

For monitoring purposes, LDH is relevant in predicting disease activity in leukemias and the probability of survival in Hodgkin’s disease and non-Hodgkin’s lymphomas.

Patients with malignant disease often show increases in serum LDH; up to 70% of patients with liver metastases and 20–60% of patients with other metastases (e.g., lymph nodes) show increased LDH activity. Increased LDH-1 is observed in germ cell tumors (∼60% of cases), such as teratoma, testicular seminoma, and dysgerminoma of the ovary. The percentage of patients with increased LDH depends on the stage of the disease. LDH also appears to be a useful predictor of outcome in patients with nonseminomatous germ cell tumors of the testis, melanoma, and pulmonary microcytoma.

Increases in LDH are observed in hepatopathies, but their clinical use in a liver profile appears very limited because they do not add significant information to the determination of transaminases. Finally, measurement of LDH in pleural f luid (better if in combination with serum LDH) helps to dis tinguish between exudative (pleural fluid/LDH serum LDH >0.6) and transudative effusions (ratio <0.6).

The presence of macro-LDH due to the formation of an autoantibody–enzyme complex that leads to a persistent increase in the amount of circulating enzyme is estimated to occur in <1 person each 10,000. Its presence should be checked in suspected individuals to avoid further in-depth investigation or unnecessary treatment.

Reference Intervals

The reference interval of LDH in adult Caucasian subjects is 125–220 U/L, whereas Asian individuals show slightly higher values. The reference intervals are markedly higher in children, with a gradual decrease observed throughout the childhood period.

مواضيع ذات صلة

Fetal hemoglobin (Kleihauer–Betke)

Fetal fibronectin (fFN, Fibronectin)

Ferritin

Fecal calprotectin

Estrogen fractions (Estriol excretion, Estradiol, Estrone)

Erythropoietin (EPO)

Erythrocyte sedimentation rate (ESR, Sed rate test)

Epstein-Barr virus testing (EBV antibody titer)

Diabetes mellitus autoantibody panel (diabetes associated autoantibodies, Insulin autoantibody [IAA], Islet cell antibody [ICA], Glutamic acid decarboxylase antibody [GAD Ab])

Pancreatic Enzymes ( Lipase & Amylase )

Alkaline Phosphatase

D-dimer (Fragment D-dimer, Fibrin degradation product [FDP], Fibrin split products)