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| − | __NOTOC__
| + | 0605 http://manualss7iy.pp.ua/bnwrwn1.html http://manualss7iy.pp.ua/xpem2.html http://documentsoex.pp.ua/tsq1.html http://documentsoex.pp.ua/kvxtcu2.html http://instructions9rxg.pp.ua/iiejn2.html http://instructions9rxg.pp.ua/lddpim4.html http://instruktsiya721.pp.ua/olkkpx2.html http://instruktsiya721.pp.ua/vrol1.html http://rukovodstnnr.pp.ua/mwcfk2.html http://rukovodstnnr.pp.ua/xuykyh3.html http://rukovodstnnr.pp.ua/juqpxs2.html http://rukovodstnnr.pp.ua/wil3.html http://instruktsiya5nd.pp.ua/mvcgo2.html http://instruktsiya5nd.pp.ua/ytjmtg3.html http://rukovodstvqk.pp.ua/tqu2.html http://rukovodstvqk.pp.ua/kjanan3.html |
| − | <partinfo>BBa_K200008 short</partinfo>
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| − | [http://en.wikipedia.org/wiki/Phenylalanine_hydroxylase Phenylalanine hydroxylase (PAH)] is the enzyme that breaks down [http://en.wikipedia.org/wiki/Phenylalanine phenylalanine] to [http://en.wikipedia.org/wiki/Tyrosine tyrosine]. Deficiency of this enzyme activity has been identified as one of the causes of the disorder called [http://en.wikipedia.org/wiki/Phenylketonuria phenylketonuria (PKU)]<cite>#PAH1</cite>.
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| − | Because our project aims to deliver such enzyme to the small intestine, we have also submitted a protease resistant version ([https://parts.igem.org/wiki/index.php?title=Part:BBa_K200028 BBa_K200028]).
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| − | <br>
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| − | ===Usage and Biology===
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| − | PAH works well at a PH of around 7.0 (similar to the small intestine), and it is a non-heme iron-dependent enzyme. The enzyme binds three substrates: reduced pterin (PH4), phenylalanine, and oxygen, and releases two products: tyrosine and oxidized pterin <cite>#PAH2</cite>. Furthermore, the presence of oxygen and an additional cofactor (TPNH) is required for the hydrolysis to take place <cite>#PAH4</cite>. The enzyme is stable between 7 and 40 degrees celsius<cite>#PAH2</cite> and in this range activity increases exponentially with temperature but Km (Michaelis-Menten constant) does not vary significantly between 20 and 40 degrees. The enzyme can be rendered protease resistant via full phosphorylation.<cite>#PAH3</cite>
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| − | <br>
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| − | Phenylketonuria is a condition whose prevalence varies considerably with populations. In Northern Europe for example the incidence is estimated to 1 in 10000<cite>#PAH6</cite>. At the other end of the spectrum, Turkey is estimated to have an incidence of 1 in 2600 births<cite>#PAH6</cite>. This condition is due to the inability of the individuals to catabolise essential amino acid Phenylalanine into Tyrosine. This leads to hyperphenylalaninemia in the blood which, in turn, causes damage to the brain resulting in loss of cognitive abilities and mental retardation ([http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=261600 OMIM]).
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| − | There are two different types of the disease: classical PKU and BH<sub>4</sub>-responsive PKU. The former form of the disease is linked to a deficient PAH enzyme sequence that renders the resulting protein non functional. The latter is due to a deficient co-factor BH<sub>4</sub>. Today, only the BH<sub>4</sub> can be tackled, thus encompassing only half of the phenylketonuriac population<cite>#PAH5</cite>.
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| − | As part of the Imperial iGEM 2009 [http://2009.igem.org/Team:Imperial_College_London <i>The E.ncapsulator</i>] project, we propose a new, broader therapy strategy where both the functional enzyme and cofactor are delivered to the patient.
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| − | ===Requirements===
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| − | * Works for PH 7
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| − | * Works between 7 to 40 degrees
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| − | <span class='h3bb'>Sequence and Features</span>
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| − | <partinfo>BBa_K200008 SequenceAndFeatures</partinfo>
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| − | <!-- Uncomment this to enable Functional Parameter display
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| − | ===Functional Parameters===
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| − | <partinfo>BBa_K200008 parameters</partinfo>
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| − | =References=
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| − | [http://www.ncbi.nlm.nih.gov/nuccore/NM_000277.1?report=fasta Sequence from NCBI]
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| − | <biblio>
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| − | #PAH1 pmid=2014036
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| − | #PAH2 pmid=15708798
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| − | #PAH3 pmid=8573072
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| − | #PAH4 pmid=13525410
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| − | #PAH5 pmid=14726806
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| − | #PAH6 pmid=15303001
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| − | </biblio>
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