Sandbox 181: Difference between revisions

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Ultimately, a mutation in the single-copy gene coding for GSH reductase affecting its activity would disrupt the redox state of the GSSG/2GSH in the cell. If GSH were unable to be regenerated from GSSG the cellular environment would become more oxidising, a phenomenon shown to be associated will the onset of cellular apoptosis at a moderate oxidizing environment and necrosis at higher oxidizing cellular environments<ref>PMID: 10716996 </ref>.

Heredity ~~deficiency~~ of GSH reductase is rare<ref name="Kamerbeek">PMID: 17185460 </ref>. A deficiency is most often due a genetic mutation and in two related case studies a deletion of the Asp385-Arg478 segment was found <ref name="Kamerbeek"/>. This shorted the protein to 43.8 kDA and once expressed, was likely degraded due to misfolding, leading to a deficiency of GSH reductase<ref name="Kamerbeek"/>. The symptoms and consequences in these genetically related cases were favism, cataracts, and a reduced lifespan of red blood cells<ref name="Kamerbeek"/>. The formation of cataracts in these patients was likely due to UV-induced oxidative damage to the lens of the eye<ref name="Kamerbeek"/>.

Heredity deficiencies of GSH reductase are rare<ref name="Kamerbeek">PMID: 17185460 </ref>. A deficiency is most often due a genetic mutation and in two related case studies a deletion of the Asp385-Arg478 segment was found <ref name="Kamerbeek"/>. This shorted the protein to 43.8 kDA and once expressed, was likely degraded due to misfolding, leading to a deficiency of GSH reductase<ref name="Kamerbeek"/>. The symptoms and consequences in these genetically related cases were favism, cataracts, and a reduced lifespan of red blood cells<ref name="Kamerbeek"/>. The formation of cataracts in these patients was likely due to UV-induced oxidative damage to the lens of the eye<ref name="Kamerbeek"/>.

A second mutation in the GSH reductase gene truncated GSH reductase at Trp287 by changing the TGG codon for Trp287 into a premature TGA stop codon <ref name="Kamerbeek"/>. The folding-initiating helix 11 of residues 439 to 454 is then missing, causing the improper folding and an inactive enzyme <ref name="Kamerbeek"/>. Additionally, Gly330 is exchanged for a GCG codon for alanine <ref name="Kamerbeek"/>. The exchange of glycine to alanine affects catalysis and stability of GSH reductase by disrupting the proper FAD binding necessitating the presence of higher concentrations of FAD to saturate the apoenzyme <ref name="Kamerbeek"/>.

Sandbox 181: Difference between revisions

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 Ultimately, a mutation in the single-copy gene coding for GSH reductase affecting its activity would disrupt the redox state of the GSSG/2GSH in the cell. If GSH were unable to be regenerated from GSSG the cellular environment would become more oxidising, a phenomenon shown to be associated will the onset of cellular apoptosis at a moderate oxidizing environment and necrosis at higher oxidizing cellular environments<ref>PMID: 10716996 </ref>.
-Heredity deficiency of GSH reductase is rare<ref name="Kamerbeek">PMID: 17185460 </ref>. A deficiency is most often due a genetic mutation and in two related case studies a deletion of the Asp385-Arg478 segment was found <ref name="Kamerbeek"/>. This shorted the protein to 43.8 kDA and once expressed, was likely degraded due to misfolding, leading to a deficiency of GSH reductase<ref name="Kamerbeek"/>. The symptoms and consequences in these genetically related cases were favism, cataracts, and a reduced lifespan of red blood cells<ref name="Kamerbeek"/>. The formation of cataracts in these patients was likely due to UV-induced oxidative damage to the lens of the eye<ref name="Kamerbeek"/>.
+Heredity deficiencies of GSH reductase are rare<ref name="Kamerbeek">PMID: 17185460 </ref>. A deficiency is most often due a genetic mutation and in two related case studies a deletion of the Asp385-Arg478 segment was found <ref name="Kamerbeek"/>. This shorted the protein to 43.8 kDA and once expressed, was likely degraded due to misfolding, leading to a deficiency of GSH reductase<ref name="Kamerbeek"/>. The symptoms and consequences in these genetically related cases were favism, cataracts, and a reduced lifespan of red blood cells<ref name="Kamerbeek"/>. The formation of cataracts in these patients was likely due to UV-induced oxidative damage to the lens of the eye<ref name="Kamerbeek"/>.
 A second mutation in the GSH reductase gene truncated GSH reductase at Trp287 by changing the TGG codon for Trp287 into a premature TGA stop codon <ref name="Kamerbeek"/>. The folding-initiating helix 11 of residues 439 to 454 is then missing, causing the improper folding and an inactive enzyme <ref name="Kamerbeek"/>. Additionally, Gly330 is exchanged for a GCG codon for alanine <ref name="Kamerbeek"/>. The exchange of glycine to alanine affects catalysis and stability of GSH reductase by disrupting the proper FAD binding necessitating the presence of higher concentrations of FAD to saturate the apoenzyme <ref name="Kamerbeek"/>.