Lactate Dehydrogenase

Lactate dehydrogenase (LD, LDH) is an enzyme that is found in all cells in all tissues of the body. It catalyzes the reversible conversion of lactate to pyruvic acid in glycolysis and gluconeogenesis. It is released from various anatomical sites of the body in response to cellular injury and damage. It is used as a common marker for tissue damage and disease such as heart failure. Its down-fall is that it isn’t very specific to which tissue is damaged, but there are subtle hints that can clue a physician in particular directions.

Lactate dehydrogenase is structurally composed of four subunits, but the two common subunits are LDHA known as LDH-M, and LDHB, known as LDH-H. The only difference between the two subunits is that their is an amino acid substitution of alanine with glutamine within the H subunit. This amino acid change slightly changes the biochemical properties of the two subunits slightly in that the H subunit can bind faster, but the catalytic activity of the M subunit does not deteriorate at the same rate as the H subunit, it holds well.

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The two subunit of LDH can form five isomers which are found in various sites within the body;

LDH-1 (4H)- Found in the heart, RBCs, and the brain.

LDH-2 (3H1M)- Found in the RES.

LDH-3 (2H2M)- Found in the lungs.

LDH-4 (1H3M)- Found in the kidneys, placenta, and the pancreas.

LDH-5 (4M)- Found in the liver and striated muscle.

LDH is a protein that is found in small amounts normally in the body and there are various conditions that can cause an elevation. Cancer can raise the LDH levels within the body. Cancer cells rely on increased glycolysis due to their high energy demand. LDH elevation in cancer is often times referred to the Warburg effect which allows malignant cells to convert glucose stores into lactate even in the presence of aerobic respiration. This shifts glucose metabolism from simple energy production to accelerate cell growth and proliferation.

Hemolysis can be measured as LDH is abundant in RBCs and can be measured. Although measures should be taken to correctly receive the sample as incorrect procedures an cause hemolysis and a false-positive elevation in LDH levels among other substrates and electrolytes.

It can also be used as a marker for myocardial infarction. Normally LDH-2 is at a higher level than LDH-1. When someone experiences a myocardial infarction, levels of LDH-1 will be significantly elevated to a level higher than LDH-2. This is known as the LDH flip and is diagnostic in patients who have experienced myocardial infarction. Elevation of LDH peaks 3-4 days after MI, and can remain elevated for up to 10 days. LDH has since been replaced by the troponin test, which is a much more specific and sensitive test in diagnosing MI.

High levels of LDH in the cerebrospinal fluid (CSF) can indicate bacterial meningitis. Elevated LDH levels in viral meningitis is indicative of a poor prognosis.

LDH is an important tool that physicians don’t always utilize to its lack of specificity, but it can still be helpful in a diagnosis. Its important not to ignore any test and any result as it still contributes to the whole picture.

-Caleb

 

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