Glutamate dehydrogenase
(GLDH, GMD, GLD)
Glutamate dehydrogenase (GLDH) is a mitochrondrial enzyme that catalyzes the conversion of glutamate to 2-oxoglutarate. Increases in GLDH are used to primarily 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). It is now included on our large animal (and non-mammalian) panels because it is thought to be a more stable enzyme (with storage) than SDH (which decreases rapidly in stored samples). Low values of GLDH (usually < 10 U/L) are seen in health in small animals and horses, whereas healthy cattle and alpacas may have higher values (up to 60 U/L in cattle and 20 U/L in alpacas).
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 increased in GLDH than ALT. The half-life is reported around 14 hours in cattle.
Causes of increased GLDH
Liver disease
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. Our experience with horses at Cornell University is that GLDH is usually increased concurrently with SDH in liver damage, however values 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 in some foals may be above reference intervals established for adults (similar to GGT) and may not indicate liver disease. GLDH is not increased in horses or exotics with severe muscle injury (extremely high CKs), supporting its specificity for liver disease.
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