Jasper Lactate Final: Difference between revisions
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*(4M) Muscle and Liver | *(4M) Muscle and Liver | ||
The <scene name='Jasper_Lactate_Final/Secondary/1'>secondary structure</scene> of LDH as shown here is comprised of 40% alpha helices and 23% beta sheets. | The <scene name='Jasper_Lactate_Final/Secondary/1'>secondary structure</scene> of LDH as shown here is comprised of 40% alpha helices and 23% beta sheets<ref name="2nd">http://www.cheric.org/ippage/e/ipdata/2004/05/file/e200405-701.pdf </ref>. The SCOP data classifies this form of lactate dehydrogenase as mixed beta-alpha-beta, with mainly parallel beta sheets. | ||
==Catalysis== | ==Catalysis== | ||
Studies have shown that the reaction mechanism of LDH follows an ordered sequence. In order for lactate to be oxidized NADH must bind to the enzyme first followed by lactate. Several residues are involved in the binding of NADH, including <scene name='Jasper_Lactate_Final/250_final/1'>Lys 250</scene> and <scene name='Jasper_Lactate_Final/85_final/1'>Tyr 85</scene>. Once the NADH is bound to the enzyme, it is then possible for lactate to bind. Lactate binds to the enzyme between the nicotinamide ring and <scene name='Jasper_Lactate_Final/His_195_final/1'>His 195</scene>. Transfer of a hydride ion then happens quickly in either direction giving a mixture of the two tertiary complexes, enzyme-NAD+-lactate and enzyme-NADH-pyruvate. Finally pyruvate dissociates from the enzyme followed by NAD+. | Studies have shown that the reaction mechanism of LDH follows an ordered sequence. In order for lactate to be oxidized NADH must bind to the enzyme first followed by lactate. Several residues are involved in the binding of NADH, including <scene name='Jasper_Lactate_Final/250_final/1'>Lys 250</scene> and <scene name='Jasper_Lactate_Final/85_final/1'>Tyr 85</scene>. Once the NADH is bound to the enzyme, it is then possible for lactate to bind. Lactate binds to the enzyme between the nicotinamide ring and <scene name='Jasper_Lactate_Final/His_195_final/1'>His 195</scene>. Transfer of a hydride ion then happens quickly in either direction giving a mixture of the two tertiary complexes, enzyme-NAD+-lactate and enzyme-NADH-pyruvate .Finally pyruvate dissociates from the enzyme followed by NAD+<ref name="1st"> http://www.bioc.aecom.yu.edu/labs/calllab/highlights/LDH.htm</ref>. | ||
[[Image:2nd.png|355px|(1)]] | [[Image:2nd.png|355px|(1)]] | ||
==Kinetics== | ==Kinetics== | ||
Kinetic studies of lactate dehydrogenase with oxalate and oxamate (structural analogues of lactate and pyruvate)have proven the mechanism stated above. The rate limiting step in this reaction is the rate of dissociation of NAD+ and NADH. The conversion of pyruvate to lactate with the subsequent regeneration of NAD+ is very favorable. | Kinetic studies of lactate dehydrogenase with oxalate and oxamate (structural analogues of lactate and pyruvate)have proven the mechanism stated above. The rate limiting step in this reaction is the rate of dissociation of NAD+ and NADH. The conversion of pyruvate to lactate with the subsequent regeneration of NAD+ is very favorable. | ||
[[Image:Kin.jpg|355px|(1)]] | [[Image:Kin.jpg|355px|(1)]] | ||
==Regulation== | |||
As the mechanism is one of equilibrium, There appears to be no regulation specifically designed for lactate dehydrogenase, instead it is dependent on the activation of anaerobic reparation and the presence of pyruvate and NADH, or lactate and NAD+. | |||
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==Reference== | ==Reference== | ||
1- http://www.bioc.aecom.yu.edu/labs/calllab/highlights/LDH.htm | *1- http://www.bioc.aecom.yu.edu/labs/calllab/highlights/LDH.htm | ||
2- http://www.cheric.org/ippage/e/ipdata/2004/05/file/e200405-701.pdf | *2- http://www.cheric.org/ippage/e/ipdata/2004/05/file/e200405-701.pdf | ||
*3- http://resources.metapress.com/pdf-preview.axd?code=ulnhp23038060m21&size=largest | |||
*4- http://www.u676.org/Documents/Chretien-ClinChimActa-95.pdf | |||
*5- http://www.jbc.org/content/243/17/4526.full.pdf+html | |||