Proteopedia

Jasper Small Lactate Sandbox 1: Difference between revisions

← Older edit
No edit summary
No edit summary
 
(9 intermediate revisions by the same user not shown)
Line 1: Line 1:
{{Seed}}
[[Image:1i10.png|left|200px]]
[[Image:1i10.png|left|200px]]
<!--
The line below this paragraph, containing "STRUCTURE_1i10", creates the "Structure Box" on the page.
You may change the PDB parameter (which sets the PDB file loaded into the applet)
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
or leave the SCENE parameter empty for the default display.
-->
{{STRUCTURE_1i10|  PDB=1i10  |  SCENE=  }}  
{{STRUCTURE_1i10|  PDB=1i10  |  SCENE=  }}  


Line 14: Line 6:
==Lactate Dehydrogenase==
==Lactate Dehydrogenase==


Lactate Dehydrogenase (LDH) is an important enzyme in humans. It occurs in different regions of the body, each region having a unique conformation of different subunits. The Jmole image shown is that of LDH-5, the form found in skeleton muscle and the liver.
<scene name='Jasper_Small_Lactate_Sandbox_1/Basic/1'>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. The Jmole image shown is that of LDH-5, the form found in skeleton muscle and the liver. LDH is a key enzyme in anaerobic respiration. Anaerobic Respiration is the conversion of pyruvate into lactate acid 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+. 
 
 
[[Image:LDH_reaction.jpeg|left|thumb|355px|Catalytic function of LDH (1)]]
 


==Function==
==Structure==
[[Image:LDH_reaction.jpeg|left|thumb|355px|Catalytic function of LDH]]


LDH preforms an important metabolic function in the body. The enzyme catalyzes both the conversion of pyruvate to lactose as well as the conversion of lactose to pyruvate. The conversion of pyruvate to lactose occurs in the muscles of the body when oxygen is absent. The lactate acid is then moved back to the liver where LDH catalyzes the Cori cycle which converts the lactose back into pyruvate. The reaction is also important as it is coupled with the interconversion of NADH and NAD+.
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:
*(4H) Heart
*(3H1M) Reticuloendothelial
*(2H2M) Lungs
*(1H3M) Kidneys
*(4M) Muscle and Liver
 
The secondary structure of LDH is comprised of 40% alpha helices and 23% beta sheets.(2)
SCOP
1I10- a/b Mainly parallel beta sheets (beta-alpha-beta units)
1I0Z- a/b Mainly parallel beta sheets (beta-alpha-beta units)


==Catalysis==
==Catalysis==
Studies have shown that the reaction mechanism of LDH follows an ordered sequence. In order for lactate to be oxidized NAD+ must bind to the enzyme first followed by lactate. Transfer of a hydride ion then happens quickly in either direction giving a mixture of the two teranary complexes, enzyme-NAD+-lactate and enzyme-NADH-pyruvate. Finally pyruvate dissociates from the enzyme followed by NADH. The rate limiting step in this reaction is the rate of dissociation of NADH. The same holds true in the reverse reaction that the coenzyme, NADH, must bind first before the substrate, pyruvate, can bind. The conversion of pyruvate to lactate with the subsequent regeneration of NAD+ is a very favorable(1).
Studies have shown that the reaction mechanism of LDH follows an ordered sequence. In order for lactate to be oxidized NAD+ must bind to the enzyme first followed by lactate. Transfer of a hydride ion then happens quickly in either direction giving a mixture of the two teranary complexes, enzyme-NAD+-lactate and enzyme-NADH-pyruvate. Finally pyruvate dissociates from the enzyme followed by NADH. The rate limiting step in this reaction is the rate of dissociation of NADH. The same holds true in the reverse reaction that the coenzyme, NADH, must bind first before the substrate, pyruvate, can bind. The conversion of pyruvate to lactate with the subsequent regeneration of NAD+ is a very favorable(1).


[[Image:2nd.png|left|thumb|355px|(1)]]
Important Sites:
Important Sites:
*<scene name='Jasper_Small_Lactate_Sandbox_1/His_195/1'>HIS 195</scene>
*<scene name='Jasper_Small_Lactate_Sandbox_1/His_195/1'>HIS 195</scene>
Line 30: Line 36:
*<scene name='Jasper_Small_Lactate_Sandbox_1/Arg_171/1'>ARG 171</scene>
*<scene name='Jasper_Small_Lactate_Sandbox_1/Arg_171/1'>ARG 171</scene>


==Structure==


LDH is comprized of 40% alpha helixes and 23% beta sheets.(2)


SCOP
==Reference==
1I10- a/b Mainly parallel beta sheets (beta-alpha-beta units)
1I0Z- a/b Mainly parallel beta sheets (beta-alpha-beta units)


==Reference==
<ref group="xtra">PMID:11276087</ref><references group="xtra"/>
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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Jasper Small
Retrieved from "https://proteopedia.openfox.io/w/Jasper_Small_Lactate_Sandbox_1"