https://padlet.com/hnb002/fg2eu8sdtr5taddp Made with eyes on the prize en-us 2021-10-22 21:01:33 UTC 2021-10-23 00:32:57 UTC hello@padlet.com hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837229857 Inborn Error of Phenylalanine Metabolism 

]]> 2021-10-22 21:25:35 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837229857 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837239587 Chromosome 12q23.2


]]> 2021-10-22 21:35:53 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837239587 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837241242 hepatic phenylalanine hydroxylase 
phenylalanine 4-monoocygenase]]> 2021-10-22 21:37:43 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837241242 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837250543 Conversion/breakdown  of phenylalanine using the hydroxylation of aromatic sidechains that are within phenylalanine and resulting in amino acids such as Tyrosine. The PAH gene does this with the help of BH4 (tetrahydrobiopterin)  
[2]]]> 2021-10-22 21:47:15 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837250543 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837261653 Accumulation of toxic by-products cause seizures, growth failure such as delayed development, behavioral disorders, skin rash, intellectual impairment, and microcephaly.  Also is common to have a musty order from skin, urine, and breath due to the body's attempt to excerpt the large accumulation of phenylalanine within the body.
Pregnant patients are at risk of developing the condition maternal PKU which can cause high blood phenylalanine levels which can cause serious complications in infants such as low birth weight, delayed development, facial abnormalities, heart defects, intellectually disabilities, and behavioral issues.
[2]]]> 2021-10-22 21:59:55 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837261653 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837269568 Molecular lesion associated with RFLP haplotype 2 mutant allele. This is caused by the C-T transition in exon 12 resulting in an amino acid substitution which is ARG-TRP at residue 408 of PAH [3]]]> 2021-10-22 22:09:22 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837269568 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837315117 Mutation variants such as  c.1144T>C and c.1066-3C>T cause the skipping of exon 11 whom is considered a vulnerable exon due to the weak 3' splice site. this then prevents the binding of U1snRNR70 to the intronic region as it has been disrupted by the mutation.  The U1snRNP splicing regulatory motif is what determines the succefully exon 11 splicing. Exon 11 is inclusion dependent on ESE spanning position c.1144 so when mutation occurs it inhibits the splicing process completely. [3]]]> 2021-10-22 23:11:20 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837315117 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837334574 missense mutations located outsides the consensus splicing site such as  G272X, P281L and R408Q cause exons within the transcription to be skipped either partially or fully. [1]]]> 2021-10-22 23:38:09 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837334574 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837343774 normally spliced PAH mRNA sequence results in a 957 bp from 3' end and hPAH coding region that correslates with the cDNA psotion of 451-1406 thus presenting the nromally spliced 3' end of PAH mRNA. 
PC 1
5'-GATCCTGTGTACCGTGCAAG-3' (forward, cDNA positions 452-470)
PC 2
5'-CTCCATCAACAGATTCACAGC-3' (reverse, cDNA position 1386-1406)
Common mutant fragment show the exon 8 deletion
Data collected shows that Mutant fragments contained the 842C→T mutation (P281L) of exon 7 found in the genomic DNA. [1]

]]> 2021-10-22 23:50:02 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837343774 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837347520 Is positively charged, polar, and somewhat amphipathic. It is found as part of the side chain nearest to the backbone of PAH. Only the charged portions on the outside. This is Useful in creating many hydrogen bonds. 
[4]]]> 2021-10-22 23:54:35 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837347520 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837353969 The translation shows the substitution of proteins Arg to Trp
normal exon:
-ATACCTCGGCCC-
pro407 lle406 Arg 408 pro 409
Mutated exon: 
-ATACCTTGGCCC-
lle 406 pro 407 Trp 408 pro 409
[4]



]]> 2021-10-23 00:02:33 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837353969 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837355235 Aromatic and hydrophobic.
Prefers to be buried in hydrophobic cores and helps with stacking w/aromatic side chains. 
It is a reactive and rare binding protien
[4]]]> 2021-10-23 00:04:10 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837355235 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837358886 The substitution prevents the phenylalanine hydroxylase to bind at and react with tyrosine therefore disabling the ability to break down the molecule. This then causes the build up of toxic amount of amino acids (phenylalanine) which in turn causes the symptoms of Phenylketonuria.]]> 2021-10-23 00:08:58 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837358886 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837361940 Ellingsen, S., Knappskog, P. M., Apold, J., & Eiken, H. G. (1999, September 2). Diverse PAH transcripts in lymphocytes of PKU patients with putative nonsense (G272X, Y356X) and Missense (P281L, R408Q) mutations. FEBS Press. Retrieved October 23, 2021, from https://febs.onlinelibrary.wiley.com/doi/full/10.1016/S0014-5793%2899%2901095-9?sid=nlm%3Apubmed. ]]> 2021-10-23 00:12:36 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837361940 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837364682 Williams, R. A., Mamotte, C. D. S., & Burnett, J. R. (2008, February). Phenylketonuria: An inborn error of phenylalanine metabolism. The Clinical biochemist. Reviews. Retrieved October 23, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2423317/#:~:text=Phenylketonuria%20%28PKU%29%20is%20an%20autosomal%20recessive%20inborn%20error,by%20mutations%20in%20the%20PAHgene%20on%20chromosome%2012q23.2. 

]]> 2021-10-23 00:15:47 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837364682 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837370812 Heintz C;Dobrowolski SF;Andersen HS;Demirkol M;Blau N;Andresen BS;, C. (2001, January). Splicing of phenylalanine hydroxylase (PAH) exon 11 is vulnerable: Molecular pathology of mutations in PAH exon 11. Molecular genetics and metabolism. Retrieved October 23, 2021, from https://pubmed.ncbi.nlm.nih.gov/22698810/. 

]]> 2021-10-23 00:22:43 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837370812 hnb002 https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837377816 Betts, M. J., & Russell, R. B. (2003). Trotophan. Tryptophan. Retrieved October 23, 2021, from http://www.russelllab.org/aas/Trp.html. ]]> 2021-10-23 00:30:48 UTC https://padlet.com/hnb002/fg2eu8sdtr5taddp/wish/1837377816