Sandbox Reserved 761: Difference between revisions
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'''GTP:''' | '''GTP:''' | ||
*GTP is a potent inhibitor for the reaction and binds at the base of the antenna, wedged in between the NAD binding domain and the pivot helix. This binding site is only available for GTP binding when the catalytic cleft is closed. Therefore, after GTP binds to the 'closed' conformation it is more difficult for the 'mouth' to open and release either NAD+ and NADP+ as coenzyme | *GTP is a potent inhibitor for the reaction and binds at the base of the antenna, wedged in between the NAD binding domain and the pivot helix. This binding site is only available for GTP binding when the catalytic cleft is closed. Therefore, after GTP binds to the 'closed' conformation it is more difficult for the 'mouth' to open and release either NAD+ and NADP+ as coenzyme <ref>D'Mello, J. P. F.. "Glutamate Dehydrogenase." Amino Acids in Human Nutrition and Health. 2012. 1-23. Print</ref>. | ||
'''GDP:''' | '''GDP:''' | ||
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'''ADP:''' | '''ADP:''' | ||
*In the reductive amination reaction, ADP is a potent activator at low pH and low substrate concentration. At pH 6.0, high concentrations of α-ketoglutarate and NADH, inhibit the reaction. This substrate inhibition is alleviated by ADP. Therefore, while GTP and glutamate bind synergistically with NADH to inhibit GDH, ADP activates the reaction by decreasing the affinity of the active site. However, under conditions where the enzyme is not saturated (e.g. low substrate concentrations), this loss in binding affinity causes inhibition. | *In the reductive amination reaction, ADP is a potent activator at low pH and low substrate concentration. At pH 6.0, high concentrations of α-ketoglutarate and NADH, inhibit the reaction. This substrate inhibition is alleviated by ADP. Therefore, while GTP and glutamate bind synergistically with NADH to inhibit GDH, ADP activates the reaction by decreasing the affinity of the active site. However, under conditions where the enzyme is not saturated (e.g. low substrate concentrations), this loss in binding affinity causes inhibition. | ||
*Inhibition by high [ADP] is due to competition between ADP and the adenosine moiety of the coenzyme at the active site 1. | *Inhibition by high [ADP] is due to competition between ADP and the adenosine moiety of the coenzyme at the active site 1 <ref>D'Mello, J. P. F.. "Glutamate Dehydrogenase." Amino Acids in Human Nutrition and Health. 2012. 1-23. Print</ref>. | ||
'''NADH:''' | '''NADH:''' | ||
*NADH, is another major allosteric inhibitor of GDH | *NADH, is another major allosteric inhibitor of GDH. <ref>D'Mello, J. P. F.. "Glutamate Dehydrogenase." Amino Acids in Human Nutrition and Health. 2012. 1-23. Print</ref>. | ||
'''NAD+:''' | '''NAD+:''' | ||
*This oxidized coenzyme binding causes activation | *This oxidized coenzyme binding causes activation. <ref>D'Mello, J. P. F.. "Glutamate Dehydrogenase." Amino Acids in Human Nutrition and Health. 2012. 1-23. Print</ref>. | ||
'''ATP:''' | '''ATP:''' | ||
Different concentration levels of ATP have different effects on GDH activity: | Different concentration levels of ATP have different effects on GDH activity: | ||
*Low [ATP] causes inhibition due to mediated through the GTP binding site. | *Low [ATP] causes inhibition due to mediated through the GTP binding site. <ref>PMID:11903050</ref>. | ||
*Intermediate [ATP] causes activation, mediated through the ADP effector site | *Intermediate [ATP] causes activation, mediated through the ADP effector site. <ref>PMID:11903050</ref>. | ||
*High [ATP] concentration causes inhibition due to a competition between ATP and the adenosine moiety of the coenzyme at the active site <ref>PMID:11903050</ref>. | *High [ATP] concentration causes inhibition due to a competition between ATP and the adenosine moiety of the coenzyme at the active site <ref>PMID:11903050</ref>. | ||
