PAH activity landscapes

WT/WT

Leu48Ser/Leu48Ser

Leu48Ser/Arg158Gln

Leu48Ser/Arg261Gln

Leu48Ser/Arg408Trp

Leu48Ser/IVS10-11G>A

Leu48Ser/Tyr414Cys

Ile65Thr/IVS10-11G>A

Ile65Thr/IVS12+1G>A

Arg158Gln/Arg408Trp

Arg158Gln/Tyr414Cys

Arg241His/Arg408Trp

Val245Ala/Arg408Trp

Arg252Trp/Arg252Trp

Arg252Trp/Arg408Trp

		WT
^aPeak PAH activity	2267	72658
Residual peak activity (in %)		100
^bL-phenylalanine concentration at peak activity		431
^c[S]_0.5 - Ki	-	135 - 747
^dBH4 concentration at peak activity		130
^e[C]_0.5 - Ki	-	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Arg261Gln/Arg261Gln

Arg261Gln/Arg408Trp

Arg261Gln/Glu57Lys

Arg261Gln/IVS10-11G>A

Pro281Leu/Pro281Leu

Pro281Leu/Arg408Trp

Pro281Leu/IVS10-11G>A

Ile283Phe/Arg408Trp

Arg297His/Arg408Trp

Ala300Ser/Arg408Trp

Ala300Ser/IVS10-11G>A

Ala300Ser/Pro281Leu

Ile306Val/Arg408Trp

Leu348Val/Arg408Trp

Val388Met/Arg408Trp

Glu390Gly/Arg408Trp

Ala403Val/Arg408Trp

Arg408Trp/Arg408Trp

Arg408Trp/IVS10-11G>A

Arg408Trp/IVS12+1G>A

Arg408Trp/Phe402Leu

IVS10-11G>A/IVS10-11G>A

Tyr414Cys/Arg408Trp

Tyr414Cys/IVS12+1G>A

Thr380Met/Tyr414Cys

Tyr386Cys/IVS12+1G>A

H107P/Arg261Gln

Arg68Ser/IVS12+1G>A

Ala104Asp/Ser349Pro

Asp415Asn/IVS12+1G>A

Arg243Gln/IVS12+1G>A

^a Peak PAH enzyme activity is given as [pmol L-tyrosine/min x mg protein].

^b L-phenylalanine concentration at peak activity is given as [µM].

^c [S]_0.5 - Ki indicates the optimal PAH working range (>50 % of the respective residual activity) as to substrate concentrations.

^d BH4 concentration at peak activity is given as [µM]

^e [C]_0.5 - Ki indicates the optimal PAH working range (>50 % of the respective residual activity) as to cofactor concentrations.

n. a., not applicable because no peak area was delimitable.