Biochemical reaction
The main function of lactate dehydrogenase is to catalyze the reversible oxidation of lactate (lactic acid) to pyruvate (pyruvic acid).
The successful course of this biochemical process requires the obligatory participation of a coenzyme. The oxidized form of nicotinamide adenine dinucleotide—coenzyme $NAD^+$—acts as this structural cofactor. During the oxidation of a lactic acid molecule, this coenzyme accepts electrons and protons, being reduced to $NADH$ and $H^+$.
- Equation of the catalyzed reaction: Lactate + $NAD^+$ ↔ Pyruvate + $NADH$ + $H^+$
Since the described reaction is completely reversible, the enzyme is able to function in both directions. The direction of the process at any given time is determined by the current concentration of substrates and the specific metabolic needs of a particular body tissue.
Molecular structure of the enzyme
Lactate dehydrogenase is a large oligomeric protein with a molecular mass of 134,000.
According to its 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 English words denoting the tissues where they were first discovered or where they are most actively expressed:
- H (Heart) — "heart" subunit type;
- M (Muscle) — "muscle" subunit type.
It is precisely the various combinations of these two basic types of polypeptide chains within a single tetramer that provide the structural diversity of the enzyme molecules in different organs.
LDH isoenzymes and their distribution
A random or genetically determined combination of four H and M type subunits within a single protein molecule leads to the formation of five distinct variants of lactate dehydrogenase. These variants are called isoforms (or isoenzymes). All of them catalyze the 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 of four muscle subunits only (MMMM).
Tissue distribution: The distribution of isoenzymes is strictly tissue-specific, which is of paramount importance for medicine:
- In the heart muscle (myocardium) and kidney tissues, LDH₁ and LDH₂ isoforms are overwhelmingly predominant.
- In liver tissue and skeletal muscles, LDH₄ and LDH₅ isoforms dominate.
- Other human body tissues contain different combinations and ratios of these variants.
Clinical and diagnostic significance
The key physicochemical difference between LDH isoforms lies in their different electrophoretic mobility—the speed and direction of movement in an electric field during laboratory analysis.
- The LDH₁ and LDH₂ isoforms possess fast electrophoretic mobility. During electrophoresis, they actively migrate toward the positive electrode (anode, "+").
- The LDH₄ and LDH₅ isoforms 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, a 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 differential diagnosis of diseases, blood plasma electrophoresis is performed, which reveals 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 the LDH₅ level is noted, which appears on the electropherogram as a shift of the spectrum to the right (toward the cathode).
Briefly: answers to topical questions
To which enzyme class according to the international classification does lactate dehydrogenase belong?
According to the international enzyme classification, lactate dehydrogenase belongs to class 1—oxidoreductases. It is assigned the classification number EC 1.1.1.27; the first digit of the code indicates the enzyme class. Oxidoreductases catalyze redox reactions associated with electron transfer. LDH catalyzes the reversible oxidation of lactate to pyruvate involving NAD⁺: lactate + NAD⁺ ↔ pyruvate + NADH + H⁺.
In which cell compartment (organelle) is lactate dehydrogenase localized?
Lactate dehydrogenase is localized in the cytoplasm (cytosol) of the cell. In sources, clinical diagnosis of cell damage is described as being based on the release of cytoplasmic enzymes and proteins into the blood upon membrane disruption; LDH is indicated among such markers.
For quick memorization of the extreme isoforms, rely on the English names of the subunits: "H" (Heart) forms the first isoenzyme LDH₁ (purely cardiac, HHHH), and "M" (Muscle) forms the fifth isoenzyme LDH₅ (purely muscular/hepatic, MMMM).
Class and exam questions
What specific biochemical reaction does LDH catalyze?
The enzyme carries out the reaction of reversible oxidation of lactic acid (lactate) to pyruvic acid (pyruvate). The coenzyme NAD+ is essential for this process, being reduced to NADH and H+.
What is the tetrameric structure of lactate dehydrogenase?
This means that the enzyme molecule (an oligomeric protein with a mass of 134,000) consists of four separate polypeptide chains—subunits. They can be of two types: H (heart) or M (muscle).
How does the LDH spectrum change in myocardial infarction and why?
When heart muscle cells die, a large amount of LDH₁ and LDH₂ isoforms enters the blood. On the blood plasma electropherogram, this manifests as a characteristic shift of the spectrum to the left, as these fractions have fast mobility toward the anode.
Which enzyme isoforms are characteristic of liver damage?
Liver diseases, such as hepatitis, are characterized by a sharp increase in the blood level of the LDH₅ isoform. During electrophoresis, this causes a shift of the spectrum to the right (closer to the cathode).
What else to study on this topic
- Mechanism of coenzyme NAD+ reduction during redox reactions
- Principles of blood plasma protein separation by electrophoresis
- Comparative characteristics of electropherograms of a healthy individual and a patient with myocardial infarction
- Features of lactate and pyruvate metabolism in skeletal muscles and liver
- Spatial structure of oligomeric proteins and the significance of intersubunit interactions
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