Sandbox Reserved 761: Difference between revisions

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[[Image:traces.jpg|frame|left|Figure 1. Image of Glutamate Dehydrogenase]]

'''Glutamate Dehydrogenase''' (GDH) is a homohexameric enzyme found in ~~all organisms~~ that catalyses the reversible oxidative deamination of L-glutamate to α-ketoglutarate, and vice versa using NAD+ and/or NADP+ as ~~coenzyme~~. Located in the mitochondria, GDH plays a key role in urea synthesis, nitrogen and glutamate (Glu) metabolism, and the energy homeostasis. In humans,GDH is expressed at high levels in liver, brain, pancreas and kidney. Acting as an oxidoreductase (Enzyme Class I) , GDH catalyzes the reversible NAD (P)+-linked oxidative deamination of L-glutamate into alpha ketoglutarate and ammonia in two steps. The first step involves a Schiff base intermediate being formed between ammonia and alpha ketoglutarate. This Schiff base intermediate ~~is crucial because it~~ establishes the alpha carbon atom in glutamate’s stereochemistry. The second step involves the Schiff base intermediate being protonated, which is done by the transfer of a hydride ion from NADPH resulting in L-glutamate. GDH is unique because it is able to utilize both NAD+ and NADP+ <ref>Stryer (Ed.). Biochemistry (5th Ed.) 2002. W.H. Freeman and Company, New York.</ref>. NADP+ is utilized in the forward reaction of alpha ketogluterate and free ammonia, which are converted to L-glutamate via a hydride transfer from NADPH to glutamate (15). NAD+ is utilized in the reverse reaction, which involves L-glutamate being converted to alpha ketoglutarate and free ammonia via an oxidative deamination reaction <ref>PMID:9405044</ref>. The extensive production of ammonia by peripheral tissue or glutamate dehydrogenase is not allowed because of the highly toxic effects of circulating ammonia in cells. As a result, the ammonia produced in the reverse reaction of GDH is excreted as NH4+ in the urine, by first going through the urea cycle.

'''Glutamate Dehydrogenase''' (GDH) is a homohexameric enzyme found in most microbes and eukaryotes that catalyses the reversible oxidative deamination of L-glutamate to α-ketoglutarate, and vice versa using NAD+ and/or NADP+ as cofactos. Located in the mitochondria, GDH plays a key role in urea synthesis, nitrogen and glutamate (Glu) metabolism, and the energy homeostasis. In humans,GDH is expressed at high levels in the liver, brain, pancreas and kidney. Acting as an oxidoreductase (Enzyme Class I) , GDH catalyzes the reversible NAD (P)+-linked oxidative deamination of L-glutamate into alpha ketoglutarate and ammonia in two steps. The first step involves a Schiff base intermediate being formed between ammonia and alpha ketoglutarate. This Schiff base intermediate establishes the alpha carbon atom in glutamate’s stereochemistry. The second step involves the Schiff base intermediate being protonated, which is done by the transfer of a hydride ion from NADPH resulting in L-glutamate. In it's mechanism, GDH is unique because it is able to utilize both NAD+ and NADP+ <ref>Stryer (Ed.). Biochemistry (5th Ed.) 2002. W.H. Freeman and Company, New York.</ref>. NADP+ is utilized in the forward reaction of alpha ketogluterate and free ammonia, which are converted to L-glutamate via a hydride transfer from NADPH to glutamate (15). NAD+ is utilized in the reverse reaction, which involves L-glutamate being converted to alpha ketoglutarate and free ammonia via an oxidative deamination reaction <ref>PMID:9405044</ref>. The extensive production of ammonia by peripheral tissue or glutamate dehydrogenase is not allowed because of the highly toxic effects of circulating ammonia in cells. As a result, the ammonia produced in the reverse reaction of GDH is excreted as NH4+ in the urine, by first going through the urea cycle.

==Glutamate Dehydrogenase Structure==

Sandbox Reserved 761: Difference between revisions

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 [[Image:traces.jpg|frame|left|Figure 1. Image of Glutamate Dehydrogenase]]
-'''Glutamate Dehydrogenase''' (GDH) is a homohexameric enzyme found in all organisms that catalyses the reversible oxidative deamination of L-glutamate to α-ketoglutarate, and vice versa using NAD+ and/or NADP+ as coenzyme. Located in the mitochondria, GDH plays a key role in urea synthesis, nitrogen and glutamate (Glu) metabolism, and the energy homeostasis. In humans,GDH is expressed at high levels in liver, brain, pancreas and kidney. Acting as an oxidoreductase (Enzyme Class I) , GDH catalyzes the reversible NAD (P)+-linked oxidative deamination of L-glutamate into alpha ketoglutarate and ammonia in two steps.  The first step involves a Schiff base intermediate being formed between ammonia and alpha ketoglutarate.  This Schiff base intermediate is crucial because it establishes the alpha carbon atom in glutamate’s stereochemistry.  The second step involves the Schiff base intermediate being protonated, which is done by the transfer of a hydride ion from NADPH resulting in L-glutamate.  GDH is unique because it is able to utilize both NAD+ and NADP+ <ref>Stryer (Ed.). Biochemistry (5th Ed.) 2002. W.H. Freeman and Company, New York.</ref>.  NADP+ is utilized in the forward reaction of alpha ketogluterate and free ammonia, which are converted to L-glutamate via a hydride transfer from NADPH to glutamate (15).  NAD+ is utilized in the reverse reaction, which involves L-glutamate being converted to alpha ketoglutarate and free ammonia via an oxidative deamination reaction <ref>PMID:9405044</ref>.  The extensive production of ammonia by peripheral tissue or glutamate dehydrogenase is not allowed because of the highly toxic effects of circulating ammonia in cells.  As a result, the ammonia produced in the reverse reaction of GDH is excreted as NH4+ in the urine, by first going through the urea cycle.
+'''Glutamate Dehydrogenase''' (GDH) is a homohexameric enzyme found in most microbes and eukaryotes that catalyses the reversible oxidative deamination of L-glutamate to α-ketoglutarate, and vice versa using NAD+ and/or NADP+ as cofactos. Located in the mitochondria, GDH plays a key role in urea synthesis, nitrogen and glutamate (Glu) metabolism, and the energy homeostasis. In humans,GDH is expressed at high levels in the liver, brain, pancreas and kidney. Acting as an oxidoreductase (Enzyme Class I) , GDH catalyzes the reversible NAD (P)+-linked oxidative deamination of L-glutamate into alpha ketoglutarate and ammonia in two steps.  The first step involves a Schiff base intermediate being formed between ammonia and alpha ketoglutarate.  This Schiff base intermediate establishes the alpha carbon atom in glutamate’s stereochemistry.  The second step involves the Schiff base intermediate being protonated, which is done by the transfer of a hydride ion from NADPH resulting in L-glutamate.  In it's mechanism, GDH is unique because it is able to utilize both NAD+ and NADP+ <ref>Stryer (Ed.). Biochemistry (5th Ed.) 2002. W.H. Freeman and Company, New York.</ref>.  NADP+ is utilized in the forward reaction of alpha ketogluterate and free ammonia, which are converted to L-glutamate via a hydride transfer from NADPH to glutamate (15).  NAD+ is utilized in the reverse reaction, which involves L-glutamate being converted to alpha ketoglutarate and free ammonia via an oxidative deamination reaction <ref>PMID:9405044</ref>.  The extensive production of ammonia by peripheral tissue or glutamate dehydrogenase is not allowed because of the highly toxic effects of circulating ammonia in cells.  As a result, the ammonia produced in the reverse reaction of GDH is excreted as NH4+ in the urine, by first going through the urea cycle.
 ==Glutamate Dehydrogenase Structure==