Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamic dehydrogenase (GDH) activity in rat heart was found to be 2.1 U/g of heart (wet wt). The mitochondrial glutamic dehydrogenase activity accounted for only 18% of the total. This percentage of the total activity in heart mitochondria was not altered by nagarse treatment, acetone extraction, sonication in Triton X-100, and extraction with buffer containing a protease inhibitor. The remainder of the activity was present in the cytosol. Cytosolic GDH activity differed from mitochondrial GDH activity by its pH curve, stability to heat, Arrhenius plot, and the effect of different nucleotides. Acetone extraction of the mitochondria resulted in GDH that was stable to heat and had a shallow temperature activation curve resembling cytosolic GDH. Acetone extraction of cytosolic GDH inactivated it. The cytosolic activity was purified 288-fold and the mitochondrial activity 100-fold. Purified cytosolic and mitochondrial GDH enzymes had different monomeric molecular weights on sucrose density gradient centrifugation. Gel filtration of cytosolic and mitochondrial GDH also showed different monomeric molecular weights. We conclude that rat heart GDH exists in two forms with different physical and kinetic characteristics. The majority of GDH activity in rat heart is cytosolic. The mitochondrial enzyme has a lipid-soluble component that can be removed with acetone without destroying its activity.
 ...
PMID:Glutamic dehydrogenase activity in rat heart: demonstration of two forms of enzyme activity. 672 Sep 7

Glutamate is believed to be an excitatory amino acid neurotransmitter in the retina. Enzymes for glutamate metabolism, such as glutamate dehydrogenase, ornithine aminotransferase, glutaminase, and aspartate aminotransferase (AAT), exist mainly in the mitochondria. The abnormal increase of intracellular calcium ions in ischemic retinal cells may cause an influx of calcium ions into the mitochondria, subsequently affecting various mitochondrial enzyme activities through the activity of mitochondrial calpain. As AAT has the highest level of activity among enzymes involved in glutamate metabolism, we investigated the change of AAT activity in ischemic and hypoxic rat retinas and the protection against such activity by calpain inhibitors. We used normal RCS (rdy+/rdy+) rats. For the in vivo studies, we clamped the optic nerve of anesthetized rats to induce ischemia. In the in vitro studies, the eye cups were incubated with Locke's solution saturated with 95% N2/5% CO2. The activity of cytosolic AAT (cAAT) was about 20% of total activity, whereas mitochondrial AAT (mAAT) was about 75% in rat retina. Ninety minutes of ischemia or hypoxia caused a 20% decrease in mAAT activity, whereas cAAT activity remained unchanged. To examine the contribution of intracellular calcium ions to the degradation of mAAT, we used Ca2+-free Locke's solution containing 1 mM EGTA, ryanodine (Ca2+ channel blocker), and thapsigargin (Ca2+-ATPase inhibitor). In the present study, thapsigargin in Ca2+-free Locke's solution, but not ryanodine in this solution, was found to prevent AAT degradation. AAT degradation was also prevented by calpain inhibitors (Ca2+-dependent protease inhibitor) such as calpeptin at 1 nM, 10 nM, 0.1 microM, 1 microM and 10 microM, and by calpain inhibitor peptide, but not by other protease inhibitors (10 microM leupeptin, pepstatin, chymostatin). Additionally, we determined the subcellular localization of calpain activity and examined the change of calpain activity in ischemic rat retinas. Our results suggest that decreased activity of mAAT in ischemic and hypoxic rat retinas might be evoked by the degradation by calpain-catalyzed proteolysis in mitochondria.
 ...
PMID:Possible mechanism for the decrease of mitochondrial aspartate aminotransferase activity in ischemic and hypoxic rat retinas. 1039 49