Sandbox89220: Difference between revisions

Both PMM1 and PMM2 are grouped under the haloacid dehydrogenase family, which has 4 characteristic motifs that are highly conserved in both PMMs. The phylegenic analysis of PMMs in 26 species of animals reveals a good complementary data to explain the divergence of the functions between these so closely related proteins in humans. Apparently, in the early stages of evolution of vertebrates or before the divergence of vertebrates, there are the duplication events of the PMM gene in the common vertebrates’ ancestor. The duplication allows extra set of genomic information to be passed on and mutations to occur, which later leads to the emergence of the similar yet distinct PMM1 and PMM2<ref name="Evolutionary history" />. Judging from the higher degree of identity between certain yeast type and human’s PMM2,it's said that PMM2 evolves more slowly than PMM1. As a matter of fact, with the different evolutionary rates after duplication, it allows the PMM1 and PMM2 to have diverged functions in their active sites which have some degree of conservations throughout the evolutionary lineage. It doesn't escape the attention that there are different residues replacement in primary and secondary specificity loop in the highly conserved motifs 1 and 2 in both proteins. For example, while PMM1 can be stimulated by IMP in the brain to increase its phosphatase activity (as glucose-1,6- bisphosphatase) and has decreased activity as phosphomutase by then, IMP is shown to has no effect on both the phosphatase and phosphomutase activity of PMM2. Again, it’s obvious that the evolutionary development of the PMM genes after duplication results in these two similar yet distinct proteins.

PMM2 is very critical during the early development of embryo, it's shown in experiment that the disruption of the genes causes the embryonic lethality. Also, the homozygosity of R141H (mutated allele) on the PMM2 gene is incompatible with life. In addition, it's reported that wide spectrum of clinical manifestations is due to different mutation sites on the PMM2 genes, certain mutations are demographically specific, however, the most common mutation is the R141H amongst the patients from all around the world<ref>Quelhas et al.,Congenital Disorder of Glycosylation Type Ia: Searching

for the Origin of Common Mutations in PMM2[http://onlinelibrary.wiley.com/doi/10.1111/j.1469-1809.2006.00334.x/pdf]</ref>. The patients will show psychomotoric retardation, muscle hypotonia, abnormal eye movements, inverted nipples, abnormal adipose tissue distribution, and slightly enlarged liver<ref>Presentation of congenital disorders of glycosylation type 1a[http://ovidsp.tx.ovid.com/sp-3.4.0b/ovidweb.cgi?WebLinkFrameset=1&S=POBMFPKBJHDDKEEJNCCLCAMCPPNGAA00&returnUrl=ovidweb.cgi%3f%26Full%2bText%3dL%257cS.sh.15.16%257c0%257c00006565-201003000-00011%26S%3dPOBMFPKBJHDDKEEJNCCLCAMCPPNGAA00&directlink=http%3a%2f%2fgraphics.tx.ovid.com%2fovftpdfs%2fFPDDNCMCCAEJJH00%2ffs047%2fovft%2flive%2fgv024%2f00006565%2f00006565-201003000-00011.pdf&filename=Presentation+of+Congenital+Disorders+of+Glycosylation+Type+1a.&pdf_key=FPDDNCMCCAEJJH00&pdf_index=/fs047/ovft/live/gv024/00006565/00006565-201003000-00011]</ref>.