Sandbox Reserved 1549: Difference between revisions

VLCDA clinical mutation can lead to a disease state. VLCAD is used to break down very long-chain fatty acids, and they are found in food and body’s fat tissue <ref name="VLCAD deficiency">VLCAD deficiency - Genetics Home Reference https://ghr.nlm.nih.gov/condition/very-long-chain-acyl-coa-dehydrogenase-deficiency</ref>. Fatty acids play a crucial role which provides energy for heart and muscle  <ref name="Crystal Structure of human very long-chain VLCAD"/>. Thus, VLCAD deficiency can cause severe neonatal cardiomyopathy and liver failure which occur mostly in adolescence or adulthood <ref name="Crystal Structure of human very long-chain VLCAD">crystal structure of human very-long-chain acyl-CoA dehydrogenase. The Journal of biological chemistry, 283(14), 9435–9443. doi:10.1074/jbc.M709135200. Retrieved April 30, 2019, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2431035/</ref>. In addition, if the body does not have sufficient amount of VLCAD, it would affect the metabolism of the body <ref name="VLCAD deficiency"/>. There are several mutation sites that have been found. Mutation R429W is severe in childhood phenotype <ref name="Crystal Structure of human very long-chain VLCAD"/>. <scene name='80/806435/Helixk/1'>Arg-429</scene> on the helix K makes salt-bridge with <scene name='80/806435/Helixk/1'>Glu-384</scene> on helix I  <ref name="Crystal Structure of human very long-chain VLCAD"/>. The enzyme is destabilized, and the salt bridge is broken due to the replacing charged residue with the bulky neutral residue  <ref name="Crystal Structure of human very long-chain VLCAD"/>. Another mutation site is R416H which is found on the helix J  <ref name="Crystal Structure of human very long-chain VLCAD"/>. Both sites,<scene name='80/806435/Gln422/1'> R429W and R416H</scene>, are located close to the <scene name='80/806435/Gln422/1'> catalytic glutamate</scene>  <ref name="Crystal Structure of human very long-chain VLCAD"/>. Site R416H has <scene name='80/806435/Helixj/1'>Arg-416 interacts with Asp-391 by making salt bridge</scene> and interacts <scene name='80/806435/Helixj/1'>Gln-395 through hydrogen bond</scene> <ref name="Crystal Structure of human very long-chain VLCAD"/>. Mutation in R416H causes the problem to the position of helix J  <ref name="Crystal Structure of human very long-chain VLCAD"/>. Furthermore, forming a salt bridge with the opposing monomer can affect the dimer interaction  <ref name="Crystal Structure of human very long-chain VLCAD"/>.