Glutamate-dehydrogenase

Glutamate dehydrogenase (EC 1.4.1.3 L-glutamate NAD(P) oxidoreductase, deaminating GLD) is a mitochondrial enzyme found mainly in the liver, heart muscle, and kidneys, but small amounts occur in other tissue, including brain and skeletal muscle tissue, and in leukocytes. 

Although NAD is the preferred coenzyme, NADP also acts as the hydrogen acceptor. GLD is inhibited by metal 

GLD is increased in serum of patients with hepatocellular damage. Fourfold or fivefold elevations are seen in chronic hepatitis in cirrhosis, increases are only up to twofold. Very large rises in serum GLD occur in halothane toxicity, and notable increases occur in response to some other hepato-toxic agents. 

GLD potentially offers differential diagnostic potential in the investigation of liver disease, particularly when interpreted in conjunction with other enzyme test results. The key to this differential diagnostic potential is to be found in the intraorgan and intracellular distribution of the enzyme. As an exclusively mitochondrial isoenzyme, GLD is released firom necrotic cells therefore, when compared with hepatic disorders with extensive necrosis, release is less in diffuse inflammatory processes, and in these conditions, the release of cytoplasmic enzymes, such as ALT, is quantitatively more pronounced. Together with m-AST, GLD is of value in estimation of the severity of liver cell damage. 

GLD is more concentrated in the central areas of the liver lobules than in the periportal zones. This pattern of distribution is the reverse of that of ALT. Pronounced release of GLD is therefore to be expected in conditions in which cen-trilobular necrosis occurs (e.g., as a result of ischemia or in halothane toxicity). 

TRANSLATIONAL MECHANISTIC BIOMARKERS AND MODELS FOR PREDICTING DRUG-INDUCED LIVER INJURY 

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Abass and colleagues developed an amperometric biosensor for NHA that uses the enzyme glutamate dehydrogenase to catalyze the following reaction. 

L-glutamate dehydrogenase L-glutamate test for citric acid cycle... 

Other bacteria such as E. coli assimilate ammonia by incorporating it directly into a-oxoglutarate in a reaction catalysed by glutamate dehydrogenase (GDH). This reaction can be written as... 

Energy-linked transhydrogenase, a protein in the inner mitochondrial membrane, couples the passage of protons down the electrochemical gradient from outside to inside the mitochondrion with the transfer of H from intramitochondrial NADH to NADPH for intramitochondrial enzymes such as glutamate dehydrogenase and hydroxylases involved in steroid synthesis. 

Figure 22-4. Sequence of reactions in the oxidation of unsaturated fatty acids, eg, linoleic acid. A -c/s-fatty acids or fatty acids forming A -c/s-enoyl-CoA enter the pathway at the position shown. NADPH for the dienoyl-CoA reductase step is supplied by intramitochondrial sources such as glutamate dehydrogenase, isocitrate dehydrogenase,and NAD(P)H transhydrogenase.

The enzymes glutamate dehydrogenase, glutamine synthetase, and aminotransferases occupy central positions in amino acid biosynthesis. The combined effect of... 

Figure 29-5. The i-glutamate dehydrogenase reaction. NAD(P) means that either NAD or NADP can serve as co-substrate. The reaction is reversible but favors glutamate formation.

Transamination channels a-amino acid nitrogen into glutamate. L-Glutamate dehydrogenase (GDH) occupies a central position in nitrogen metabolism. 

L)-Phosphinotricin 67, which is the active component of naturally occurring antibiotic biolaphos, was synthesized from the corresponding keto acid 66 via reductive amination catalysed by L-glutamate dehydrogenase (EDH) (Equation 32)7 ... 

Kjellberg S, M Hermansson, P Marden, GW Jones (1987) The transient phase between growth and nongrowth of heterotrophic bacteria with emphasis on the marine environment. Annu Rev Microbiol 41 25-49. Klump H, J Di Ruggiero, M Kessel, J-B Park, MWW Adams, FT Robb (1992) Glutamate dehydrogenase from the hyperthermophile Pyrococcus furiosus. Thermal denaturation and activation. J Biol Chem 267 22681-22685. 

S. E. Smith, B. L. St John, F. A. Smith, and D. j. D. Nicholas, Activity of glutamine synthetase and glutamate dehydrogenase in Trifolium subterraneum and Allium cepa L., effects of mycorrhizal infection and phosphorus nutrition. New Phytologist 99 211 (1985). 

Skuce, P.J., Stewart, E.M., Smith, W.D. and Knox, D.P. (1999a) Cloning and characterisation of glutamate dehydrogenase (GDF1) from the gut of Haemonchus contortus. Parasitology 118, 297-304. 

Nicotinamide Adenine Dinucleotide phosphate (NADP+) Glutamate dehydrogenase, Alcohol dehydrogenase, Aryl-aldehyde dehydrogenase... 

Cordek J., Wang X., Tan W., Direct immobilization of glutamate dehydrogenase on optical fiber probes for ultrasensitive glutamate detection, Anal. Chem. 1999 71 1529-1533. 

Fahien, L.A., Ruoho, A.E., and Kmiotek, E. (1978) A study of glutamate dehydrogenase aminotransferase complexes with a bifunctional imidate. ]. Biol. Cbem. 253, 5745-5751. 

Connections From amino groups of amino acids through glutamate and glutamate dehydrogenase... 

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