GLDH

 
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Physiology

Glutamate dehydrogenase (GLDH, GMD, GLD, and GDH) is a mitochrondrial enzyme that catalyzes the conversion of glutamate to 2-oxoglutarate. Increases in GLDH activity are used primarily to reflect leakage from damaged or necrotic hepatocytes. Since it is quite a large mitochondrial enzyme, injury needs to be sufficiently severe to damage mitochondria. GLDH is a useful enzyme for hepatocellular injury in large animals and exotic species (birds, amphibians, reptiles). Low activity of GLDH (usually < 10 U/L) are seen in health in small animals and horses, whereas healthy cattle and alpacas may have higher activity (up to 60 U/L in cattle and 20 U/L in alpacas). The half life of GLDH is about 8 hours in the dog, 12-24 hours in the horse and 14 hours in cattle.

Organ specificity

GLDH is found in many tissues in the body, including hepatocytes, kidney, intestine, muscle, and salivary gland. However, most of serum GLDH originates from hepatocytes (in health and disease states). GLDH is located more in the centrilobular areas of the liver, whereas AST is more homogenously distributed and ALT is more periportal in rats. Due to its preferential location in centrilobular areas, liver injury involving these areas (e.g. hypoxia) may result in higher activity of GLDH than ALT. The half-life is reported around 14 hours in cattle.

Method

The following photometric method is used at Cornell University.

Reaction type

Kinetic

Procedure

As NADH is oxidised, the rate of decrease in absorbance is measured photometrically and is proportional to the GLDH activity. The reaction is shown below.

α-oxoglutarate + NADH + NH4+  GLDH > glutamate + NAD+ + H2O

Units of measurement

GLDH activity is reported in U/L. One unit of GLDH is the amount of enzyme that will generate 1 μmol of NADH per minute at pH 7.6 at 37 °C.

Sample considerations

Sample type

Serum, plasma

Stability

GLDH is a component of the current Large Animal and Non-mammalian Chemistry Profile offered by the clinical pathology laboratory at Cornell. This is because it is thought to be a more stable enzyme (with storage) than SDH (which decreases rapidly in stored samples).

Interferences

  • Lipemia, hemolysis, and icterus: The effects of these interferents on GLDH are currently unknown.

Test interpretation

Increased activity

  • Physiologic: GLDH activity in some foals may be above reference intervals established for adults (similar to GGT) and may not indicate liver injury (unpublished observations).
  • Pathophysiologic:
    • Liver injury: GLDH is a sensitive and specific marker of liver disease in all animals, including non-mammalian species. In rats, increases in GLDH were greater in magnitude, persisted longer or occurred without concurrent increases in ALT in drug-induced hepatic injury. In calves, horses and sheep, changes in GLDH paralleled changes in SDH after acute injury induced by chloroform. Activity generally peaked at 1-2 days and then decreased to reference intervals within 4-9 days (Barakat and Ford 1988). Our experience with horses at Cornell University is that GLDH is usually increased concurrently with SDH in liver damage, however activities often remain above reference intervals for longer (therefore, it may be a more sensitive marker of persistent liver injury than SDH) and the magnitude of increase is greater than with SDH.  GLDH activity is not increased in horses or exotic animals with severe muscle injury (extremely high CK activity), supporting its specificity for liver injury. Like SDH, GLDH is not specific as to the cause of liver injury.

Decreased activity

This is not of clinical relevance.
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