Lactate dehydrogenase (LDH) isoenzymes

Lactate dehydrogenase (LDH) is an enzyme primarily involved in converting pyruvate to lactate (and vice versa). It has five isoenzymes (LDH-1 to LDH-5), each consisting of different combinations of two subunits: H (heart) and M (muscle). Further, there are individual LDH isoforms - LDH-A/B/C which make up these isoenzymes. These isoforms have specific roles / functions. LDH is also a metalloenzyme, affected by zinc status and NAD+:NADH ratio. LDH isoenzymes are distributed across various tissues based on their metabolic needs.

The terms "H" (heart) and "M" (muscle) subunits were historically named based on the tissues where these subunits were first observed in high concentrations. The H (heart) subunit was first identified in cardiac tissue, which relies on aerobic metabolism. The M (muscle) subunit was discovered in skeletal muscle, which often utilizes anaerobic glycolysis, especially during high activity.

This test allows you to see if an elevation of a specific isoenzyme or pattern of elevations is present, further suggesting if a particular tissue is experiencing energy metabolism dysregulation, and/or upstream  influences affecting energy metabolism.

eg. If LDH-4 and LDH-5 (which contain more M subunits, characteristic of anaerobic glycolysis) are elevated, it can be indicative of reduced oxygen availability or prolyl hydroxylase inhibition for other reasons (oxidative stress, low Fe/Si, low Zn, low alpha-ketoglutarate, elevated succinate). These isoenzymes are more prevalent in tissues that rely on anaerobic metabolism, such as skeletal muscle and liver, and their elevation suggests a shift towards lactate production due to reduced oxygen, a common feature of hypoxic conditions and / or various issues which inhibit prolyl hydroxylase activity (see Figure 1).