Lactate dehydrogenase, or LDH, is a protein enzyme found in almost all living cells, from bacteria to humans. Its primary job is to help convert sugar into energy for cells to use. This function is important in tissues that experience low oxygen levels, such as muscles during intense exercise, as it allows energy production to continue when oxygen is scarce.
LDH Subunit Composition
The complete LDH enzyme is a large protein constructed from smaller, individual protein chains known as subunits. LDH is a tetramer, meaning it is built from four subunits. These subunits come in two principal types, which are encoded by different genes and have slightly different structures.
The two types of subunits are designated ‘M’ and ‘H’. The ‘M’ type is predominantly produced in skeletal muscle tissue, while the ‘H’ type has a high prevalence in heart muscle. The M and H subunits possess distinct amino acid sequences, which leads to slight differences in their individual physical properties, including their molecular weight.
These structural differences also influence their enzymatic activity. The M-type subunit is more efficient at converting a molecule called pyruvate into lactate, a reaction that supports energy production in low-oxygen conditions. Conversely, the H-type subunit is better at catalyzing the reverse reaction, converting lactate back into pyruvate for use in tissues that have a steady supply of oxygen, like the heart.
The Five LDH Isoenzymes
The existence of two different subunits, M and H, allows for the formation of five distinct versions of the LDH enzyme. These different forms are called isoenzymes, or isozymes. They catalyze the same chemical reaction but have slightly different physical properties and are found in different concentrations throughout the body’s tissues.
The five isoenzymes are numbered LDH-1 through LDH-5:
- LDH-1 (H4): Composed entirely of four H subunits and is most concentrated in the heart and red blood cells.
- LDH-2 (H3M1): Consists of three H subunits and one M subunit and is also found in the heart and kidney.
- LDH-3 (H2M2): Has an even mix of two H and two M subunits and is prevalent in the lungs and other tissues.
- LDH-4 (H1M3): Contains one H subunit and three M subunits and is found in high amounts in the liver and skeletal muscle.
- LDH-5 (M4): Composed exclusively of four M subunits, this isoenzyme is the primary form found in the liver and skeletal muscle.
Determining the Overall Molecular Weight
The total molecular weight of the LDH enzyme is determined by its individual components. The H and M subunits are similar in size, with the molecular weight of each subunit being approximately 35,000 Daltons (Da), or 35 kilodaltons (kDa). A Dalton is the standard unit of mass used for atomic and molecular-scale objects.
Since every LDH isoenzyme is a tetramer, the overall molecular weight is the sum of its four parts. This calculation results in a commonly accepted value of around 140,000 Daltons, or 140 kDa, for the complete enzyme.
While the slight differences in amino acid composition between the H and M subunits create minor weight variations among the five isoenzymes, they are not significant. For instance, the H4-containing LDH-1 is marginally different in mass from the M4-containing LDH-5. However, all five versions of the enzyme cluster very closely around the 140 kDa mark, which is the value cited for the molecular weight of the LDH enzyme as a whole.