Biochemical Reaction
The primary function of lactate dehydrogenase is to catalyze the reversible oxidation of lactate to pyruvate.
This biochemical process requires the mandatory participation of a coenzyme. The oxidized form of nicotinamide adenine dinucleotide ($NAD^+$) serves as this structural cofactor. During the oxidation of lactic acid, this coenzyme accepts electrons and protons, becoming reduced to $NADH$ and $H^+$.
- Equation of the catalyzed reaction: Lactate + $NAD^+$ ↔ Pyruvate + $NADH$ + $H^+$
Because this reaction is completely reversible, the enzyme can function in both directions. The direction of the process at any given moment is determined by the current substrate concentrations and the specific metabolic demands of a given tissue.
Molecular Structure of the Enzyme
Lactate dehydrogenase is a large oligomeric protein with a molecular weight of 134,000 Da.
In terms of quaternary structure, the enzyme is a tetramer—its functionally active molecule always consists of exactly four polypeptide subunits. Two main types of subunits are synthesized in the body. Their names derive from the tissues where they were first discovered or where they are most actively expressed:
- H (Heart) — the "heart" type subunit;
- M (Muscle) — the "muscle" type subunit.
It is the various combinations of these two basic polypeptide chain types within a single tetramer that provide structural diversity to the enzyme molecules across different organs.
LDH Isoenzymes and Their Distribution
Random or genetically determined combinations of four H and M subunits within a single protein molecule result in the formation of five distinct variants of lactate dehydrogenase. These variants are called isoforms (or isoenzymes). All of them catalyze the exact same chemical reaction, but differ significantly in their physicochemical characteristics.
Classification of isoforms by subunit composition:
- LDH₁ — consists exclusively of four heart subunits (HHHH).
- LDH₂ — includes three heart and one muscle subunit (HHHM).
- LDH₃ — has an equal ratio of subunits (HHMM).
- LDH₄ — contains one heart and three muscle subunits (HMMM).
- LDH₅ — consists only of four muscle subunits (MMMM).
Tissue distribution: The distribution of isoenzymes is strictly tissue-specific, which is of paramount importance for medicine:
- In cardiac muscle (myocardium) and kidney tissues, isoforms LDH₁ and LDH₂ are absolutely predominant.
- In liver tissue and skeletal muscles, isoforms LDH₄ and LDH₅ dominate.
- In other tissues of the human body, other combinations and ratios of these variants are present.
Clinical and Diagnostic Significance
The key physicochemical difference among LDH isoforms lies in their varying electrophoretic mobility—the speed and direction of movement in an electric field during laboratory analysis.
- Isoforms LDH₁ and LDH₂ possess rapid electrophoretic mobility. During electrophoresis, they actively migrate toward the positive electrode (anode, "+").
- Isoforms LDH₄ and LDH₅ are characterized by slow mobility and remain closer to the origin line in an electric field, i.e., toward the negative electrode (cathode, "-").
In a healthy individual, normal physiological distribution of all enzyme fractions is maintained in blood plasma. However, upon cell destruction (necrosis or cytolysis), intracellular isoforms are massively released into the systemic circulation.
For the differential diagnosis of diseases, blood plasma electrophoresis is performed, which helps identify the tissue origin of the elevated fraction:
- Myocardial infarction: accompanied by the destruction of cardiomyocytes. A sharp increase in specific cardiac isoforms LDH₁ and LDH₂ is detected in the blood. On the electropherogram, this is visualized as a pronounced shift of the spectrum to the left (toward the anode).
- Hepatitis: hepatocyte death leads to the release of the hepatic fraction. A significant increase in LDH₅ levels is noted, which appears on the electropherogram as a shift of the spectrum to the right (toward the cathode).