Lactate Dehydrogenase: Difference between revisions
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<scene name='Lactate_Dehydrogenase/Cv/6'>Lactate Dehydrogenase (LDH)</scene> is an important enzyme in humans. It occurs in different regions of the body, each region having a unique conformation of different subunits. LDH is a key enzyme in anaerobic respiration. Anaerobic Respiration is the <scene name='Lactate_Dehydrogenase/Cv/4'>conversion of pyruvate into lactate acid</scene> in the absence oxygen. This pathway is important to glycolysis in two main ways. The first is that if pyruvate were to build up glycoysis and thus the generation of ATP would slow. The second is anaerobic respiration allows for the regeneration of NAD+ from NADH. NAD+ is required when glyceraldehyde-3-phosphate dehydrogenase oxidizes glyceraldehyde-3-phosphate in glycolysis, which generates NADH. Lactate dehydrogenase is responsible for the anaerobic conversion of NADH to NAD+. | <scene name='Lactate_Dehydrogenase/Cv/6'>Lactate Dehydrogenase (LDH)</scene> is an important enzyme in humans. It occurs in different regions of the body, each region having a unique conformation of different subunits. LDH is a key enzyme in anaerobic respiration. Anaerobic Respiration is the <scene name='Lactate_Dehydrogenase/Cv/4'>conversion of pyruvate into lactate acid</scene> in the absence oxygen. This pathway is important to glycolysis in two main ways. The first is that if pyruvate were to build up glycoysis and thus the generation of ATP would slow. The second is anaerobic respiration allows for the regeneration of NAD+ from NADH. NAD+ is required when glyceraldehyde-3-phosphate dehydrogenase oxidizes glyceraldehyde-3-phosphate in glycolysis, which generates NADH. Lactate dehydrogenase is responsible for the anaerobic conversion of NADH to NAD+. | ||
==Human Lactate Dehydrogenase== | |||
==Structure== | ===Structure=== | ||
LDH is a quaternary protein formed of the combination of two subunits, M and H (Muscle and Heart) into a structure of four of the subunits. The various combinations found in the human body are: | LDH is a quaternary protein formed of the combination of two subunits, M and H (Muscle and Heart) into a structure of four of the subunits. The various combinations found in the human body are: | ||
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==Catalysis== | ===Catalysis=== | ||
Studies have shown that the reaction mechanism of LDH follows an ordered sequence. [[Image:LDH_reaction.jpeg|355px|Catalytic function of LDH (1)]] 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>. | Studies have shown that the reaction mechanism of LDH follows an ordered sequence. [[Image:LDH_reaction.jpeg|355px|Catalytic function of LDH (1)]] | ||
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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)]] | ||
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[[Image:Lac.PNG]] | [[Image:Lac.PNG]] | ||
==Regulation== | ===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+. | 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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[[1hye]], [[1hyg]] – L-LDH/MDH – ''Methanocaldococcus jannaschi'' | [[1hye]], [[1hyg]] – L-LDH/MDH – ''Methanocaldococcus jannaschi'' | ||
==Additional Information== | ==Additional Information== | ||