Sandbox Reserved 1475: Difference between revisions

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[[Image:Relative efficiencies of RalDH2 for substrates.png|thumb|upright=1.5| [[Figure 5]] Relative efficiencies of RalDH2 for aldehyde substrates. Image reference.<ref name="Km value chart" />]]  
[[Image:Relative efficiencies of RalDH2 for substrates.png|thumb|upright=1.5| [[Figure 5]] Relative efficiencies of RalDH2 for aldehyde substrates. Image reference.<ref name="Km value chart" />]]  


[[Image:Retinal mm plot.png|thumb|upright=1.5| [[Figure 6]] "Rates of RA synthesis catalyzed by RalDH2 versus varying substrate concentrations. Image reference.<ref name="Km value chart" />]]


In [[Figure 5]] it is visible to see that acetaldehyde and benzaldehyde both have really high Km values, 645uM and 305uM respectfully, and relatively low Vmax values, 139nmol/min/mg and 200nmol/min/mg respectfully.<ref name="Km value chart">Wang, Xianshu. Penzes, Peter., Napoli, Joseph L., Cloning of a cDNA Encoding an Aldehyde Dehydrogenase and Its Expression in ''Escherichia coli'' RECOGNITION OF RETINAL AS SUBSTRATE. J. Biol. Chem. (1996) 271:16288-16293. doi:10.1074/jbc.271.27.16288 </ref> Octantal and decanal both have really low Km values, 5uM and 3uM respectfully, and relatively high Vmax values, 152nmol/min/mg and 214nmol/min/mg respectfully.<ref name="Km value chart" /> Acetaldehyde and benzaldehyde are both short chained aldehydes compared to octantal and decanal aldehydes. It is easier to compare the ratio of Vmax/Km. An energetically favorable substrate would display a ratio of Vmax/Km that has a large magnitude. As seen in [[Figure 5]], both the long chained octantal and decanal aldehydes had large Vmax/Km values, 152 AND 214 respectfully.<ref name="Km value chart" /> The substrate that RalDH2 uses to actually convert Vitamin A (Retinol) to retinoic acid is retinal in its "all-trans" form. As seen in [[Figure 5]] the Km value for the this substrate is the smallest out all that were tested, and the Vmax values was comparatively high. The Vmax/Km was also pretty large at a value of 49± 6.<ref name="Km value chart" />  
In [[Figure 5]] it is visible to see that acetaldehyde and benzaldehyde both have really high Km values, 645uM and 305uM respectfully, and relatively low Vmax values, 139nmol/min/mg and 200nmol/min/mg respectfully.<ref name="Km value chart">Wang, Xianshu. Penzes, Peter., Napoli, Joseph L., Cloning of a cDNA Encoding an Aldehyde Dehydrogenase and Its Expression in ''Escherichia coli'' RECOGNITION OF RETINAL AS SUBSTRATE. J. Biol. Chem. (1996) 271:16288-16293. doi:10.1074/jbc.271.27.16288 </ref> Octantal and decanal both have really low Km values, 5uM and 3uM respectfully, and relatively high Vmax values, 152nmol/min/mg and 214nmol/min/mg respectfully.<ref name="Km value chart" /> Acetaldehyde and benzaldehyde are both short chained aldehydes compared to octantal and decanal aldehydes. It is easier to compare the ratio of Vmax/Km. An energetically favorable substrate would display a ratio of Vmax/Km that has a large magnitude. As seen in [[Figure 5]], both the long chained octantal and decanal aldehydes had large Vmax/Km values, 152 AND 214 respectfully.<ref name="Km value chart" /> The substrate that RalDH2 uses to actually convert Vitamin A (Retinol) to retinoic acid is retinal in its "all-trans" form. As seen in [[Figure 5]] the Km value for the this substrate is the smallest out all that were tested, and the Vmax values was comparatively high. The Vmax/Km was also pretty large at a value of 49± 6.<ref name="Km value chart" />  
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== Disease ==
== Disease ==
[[Image:Embryo of RalDH2.png|thumb|left| [[Figure 7]] "Morphological abnormalities of RalDH2 knock out embryos".<ref name="Embryonic retinoic acid synthesis" />]]  
[[Image:Embryo of RalDH2.png|thumb|left| [[Figure 6]] "Morphological abnormalities of RalDH2 knock out embryos".<ref name="Embryonic retinoic acid synthesis" />]]  


Multiple complications can occur if there is a deficiency of RalDH2 in mammals. If there were to be a RalDH2 deficiency during the embryonic development, possible congenital malformations can occur. The complications include defects such as lack of axial rotation, incomplete neural tube closure, and lack of heart looping and chamber morphogenesis. <ref name="Embryonic retinoic acid synthesis">PMID:10192400</ref> With the study of mouse with their RalDH2 emzyne knocked out, hearts consisted of single, medial, dilated cavities.<ref name="Embryonic retinoic acid synthesis" /> The mice displayed their frontonasal region to be truncated, and their otocysts to be reduced.<ref name="Embryonic retinoic acid synthesis" /> In [[Figure 7]], the comparison of wild-type embryos compared to ones that are RalDH2 negative. It is visible to see that there is lack of embryonic turning, associated with a truncation of the posterior region.<ref name="Embryonic retinoic acid synthesis" /> The WT 8.5 doc embryo is the wild-type embryo before turning has occurred. Section b displays a wild-type embryo compared to defective embryos, section c-d. The e and f show the embryos of a wild-type embryo compared to one that was  low in the RalDH2 enzyme, respectfully.  
Multiple complications can occur if there is a deficiency of RalDH2 in mammals. If there were to be a RalDH2 deficiency during the embryonic development, possible congenital malformations can occur. The complications include defects such as lack of axial rotation, incomplete neural tube closure, and lack of heart looping and chamber morphogenesis. <ref name="Embryonic retinoic acid synthesis">PMID:10192400</ref> With the study of mouse with their RalDH2 emzyne knocked out, hearts consisted of single, medial, dilated cavities.<ref name="Embryonic retinoic acid synthesis" /> The mice displayed their frontonasal region to be truncated, and their otocysts to be reduced.<ref name="Embryonic retinoic acid synthesis" /> In [[Figure 6]], the comparison of wild-type embryos compared to ones that are RalDH2 negative. It is visible to see that there is lack of embryonic turning, associated with a truncation of the posterior region.<ref name="Embryonic retinoic acid synthesis" /> The WT 8.5 doc embryo is the wild-type embryo before turning has occurred. Section b displays a wild-type embryo compared to defective embryos, section c-d. The e and f show the embryos of a wild-type embryo compared to one that was  low in the RalDH2 enzyme, respectfully.  


== Relevance ==
== Relevance ==