WT/WT

aPeak PAH activity 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

Leu48Ser/Leu48Ser

WT
aPeak PAH activity 476972658
Residual peak activity (in %) 7100
bL-phenylalanine
concentration
at peak activity
351431
c[S]0.5 - Ki 92 - 533135 - 747
dBH4 concentration
at peak activity
146130
e[C]0.5 - Ki 37 - 46330 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Leu48Ser/Arg158Gln

WT
aPeak PAH activity 304172658
Residual peak activity (in %) 4100
bL-phenylalanine
concentration
at peak activity
330431
c[S]0.5 - Ki 78 - 542135 - 747
dBH4 concentration
at peak activity
200130
e[C]0.5 - Ki 89 - 45830 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Leu48Ser/Arg261Gln

WT
aPeak PAH activity 622972658
Residual peak activity (in %) 9100
bL-phenylalanine
concentration
at peak activity
501431
c[S]0.5 - Ki 146 - 1164135 - 747
dBH4 concentration
at peak activity
100130
e[C]0.5 - Ki 31 - 30230 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Leu48Ser/Arg408Trp

WT
aPeak PAH activity 253472658
Residual peak activity (in %) 4100
bL-phenylalanine
concentration
at peak activity
351431
c[S]0.5 - Ki 90 - 543135 - 747
dBH4 concentration
at peak activity
268130
e[C]0.5 - Ki 33 - 43230 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Leu48Ser/IVS10

WT
aPeak PAH activity 546872658
Residual peak activity (in %) 8100
bL-phenylalanine
concentration
at peak activity
391431
c[S]0.5 - Ki 103 - 556135 - 747
dBH4 concentration
at peak activity
235130
e[C]0.5 - Ki 32 - 43230 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Leu48Ser/Tyr414Cys

WT
aPeak PAH activity 281572658
Residual peak activity (in %) 4100
bL-phenylalanine
concentration
at peak activity
341431
c[S]0.5 - Ki 77 - 570135 - 747
dBH4 concentration
at peak activity
98130
e[C]0.5 - Ki 39 - 23130 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Ile65Thr/IVS10

WT
aPeak PAH activity 497872658
Residual peak activity (in %) 7100
bL-phenylalanine
concentration
at peak activity
441431
c[S]0.5 - Ki 119 - 605135 - 747
dBH4 concentration
at peak activity
409130
e[C]0.5 - Ki 43 - 42430 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Ile65Thr/IVS12

WT
aPeak PAH activity 334381647
Residual peak activity (in %) 4100
bL-phenylalanine
concentration
at peak activity
404387
c[S]0.5 - Ki 122 - 0128 - 829
dBH4 concentration
at peak activity
123131
e[C]0.5 - Ki 31 - 49731 - 490

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Arg158Gln/Arg408Trp

WT
aPeak PAH activity 247072658
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)

PhenotypeResponsiveness

Arg158Gln/Tyr414Cys

WT
aPeak PAH activity 161472658
Residual peak activity (in %) 2100
bL-phenylalanine
concentration
at peak activity
281431
c[S]0.5 - Ki 72 - 520135 - 747
dBH4 concentration
at peak activity
99130
e[C]0.5 - Ki 54 - 23530 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Arg241His/Arg408Trp

WT
aPeak PAH activity 207172658
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)

PhenotypeResponsiveness

Val245Ala/Arg408Trp

WT
aPeak PAH activity 748672658
Residual peak activity (in %) 10100
bL-phenylalanine
concentration
at peak activity
391431
c[S]0.5 - Ki 120 - 643135 - 747
dBH4 concentration
at peak activity
157130
e[C]0.5 - Ki 34 - 46830 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Arg252Trp/Arg252Trp

WT
aPeak PAH activity 269972658
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)

PhenotypeResponsiveness

Arg252Trp/Arg408Trp

WT
aPeak PAH activity 226772658
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)

PhenotypeResponsiveness

Arg261Gln/Arg261Gln

WT
aPeak PAH activity 803172658
Residual peak activity (in %) 11100
bL-phenylalanine
concentration
at peak activity
762431
c[S]0.5 - Ki 283 - 1314135 - 747
dBH4 concentration
at peak activity
94130
e[C]0.5 - Ki 28 - 24930 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Arg261Gln/Arg408Trp

WT
aPeak PAH activity 459872658
Residual peak activity (in %) 6100
bL-phenylalanine
concentration
at peak activity
752431
c[S]0.5 - Ki 252 - 1023135 - 747
dBH4 concentration
at peak activity
99130
e[C]0.5 - Ki 35 - 25830 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Arg261Gln/Glu57Lys

WT
aPeak PAH activity 3407581647
Residual peak activity (in %) 42100
bL-phenylalanine
concentration
at peak activity
371387
c[S]0.5 - Ki 117 - 128 - 829
dBH4 concentration
at peak activity
145131
e[C]0.5 - Ki 31 - 31 - 490

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Arg261Gln/IVS10

WT
aPeak PAH activity 601372658
Residual peak activity (in %) 8100
bL-phenylalanine
concentration
at peak activity
802431
c[S]0.5 - Ki 197 - 118135 - 747
dBH4 concentration
at peak activity
149130
e[C]0.5 - Ki 32 - 24730 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Pro281Leu/Pro281Leu

WT
aPeak PAH activity 226572658
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)

PhenotypeResponsiveness

Pro281Leu/Arg408Trp

WT
aPeak PAH activity 229772658
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)

PhenotypeResponsiveness

Pro281Leu/IVS10

WT
aPeak PAH activity 416372658
Residual peak activity (in %) 6100
bL-phenylalanine
concentration
at peak activity
431
c[S]0.5 - Ki - 0135 - 747
dBH4 concentration
at peak activity
130
e[C]0.5 - Ki - 030 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Ile283Phe/Arg408Trp

WT
aPeak PAH activity 253472658
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)

PhenotypeResponsiveness

Arg297His/Arg408Trp

WT
aPeak PAH activity 716272658
Residual peak activity (in %) 10100
bL-phenylalanine
concentration
at peak activity
882431
c[S]0.5 - Ki 319 - 1938135 - 747
dBH4 concentration
at peak activity
99130
e[C]0.5 - Ki 29 - 21930 - 294

Clinical Data (data from BioPKU)

Phenotype

Ala300Ser/Arg408Trp

WT
aPeak PAH activity 381972658
Residual peak activity (in %) 5100
bL-phenylalanine
concentration
at peak activity
391431
c[S]0.5 - Ki 120 - 615135 - 747
dBH4 concentration
at peak activity
135130
e[C]0.5 - Ki 30 - 46130 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Ala300Ser/IVS10

WT
aPeak PAH activity 501172658
Residual peak activity (in %) 7100
bL-phenylalanine
concentration
at peak activity
431431
c[S]0.5 - Ki 131 - 576135 - 747
dBH4 concentration
at peak activity
219130
e[C]0.5 - Ki 34 - 42930 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Ala300Ser/Pro281Leu

WT
aPeak PAH activity 652972658
Residual peak activity (in %) 9100
bL-phenylalanine
concentration
at peak activity
361431
c[S]0.5 - Ki 106 - 775135 - 747
dBH4 concentration
at peak activity
110130
e[C]0.5 - Ki 41 - 40330 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Ile306Val/Arg408Trp

WT
aPeak PAH activity 449472658
Residual peak activity (in %) 6100
bL-phenylalanine
concentration
at peak activity
271431
c[S]0.5 - Ki 64 - 513135 - 747
dBH4 concentration
at peak activity
105130
e[C]0.5 - Ki 52 - 29830 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Leu348Val/Arg408Trp

WT
aPeak PAH activity 570072658
Residual peak activity (in %) 8100
bL-phenylalanine
concentration
at peak activity
511431
c[S]0.5 - Ki 156 - 1046135 - 747
dBH4 concentration
at peak activity
215130
e[C]0.5 - Ki 31 - 33130 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Val388Met/Arg408Trp

WT
aPeak PAH activity 536572658
Residual peak activity (in %) 7100
bL-phenylalanine
concentration
at peak activity
361431
c[S]0.5 - Ki 112 - 730135 - 747
dBH4 concentration
at peak activity
159130
e[C]0.5 - Ki 32 - 37130 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Glu390Gly/Arg408Trp

WT
aPeak PAH activity 600572658
Residual peak activity (in %) 8100
bL-phenylalanine
concentration
at peak activity
501431
c[S]0.5 - Ki 150 - 770135 - 747
dBH4 concentration
at peak activity
100130
e[C]0.5 - Ki 30 - 28830 - 294

Ala403Val/Arg408Trp

WT
aPeak PAH activity 644472658
Residual peak activity (in %) 9100
bL-phenylalanine
concentration
at peak activity
251431
c[S]0.5 - Ki 52 - 510135 - 747
dBH4 concentration
at peak activity
100130
e[C]0.5 - Ki 44 - 22630 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Arg408Trp/Arg408Trp

WT
aPeak PAH activity 127372658
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)

PhenotypeResponsiveness

Arg408Trp/IVS10

WT
aPeak PAH activity 291972658
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)

PhenotypeResponsiveness

Arg408Trp/IVS12

WT
aPeak PAH activity 271472658
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)

PhenotypeResponsiveness

Arg408Trp/Phe402Leu

WT
aPeak PAH activity 328281647
Residual peak activity (in %) 4100
bL-phenylalanine
concentration
at peak activity
488387
c[S]0.5 - Ki 150 - 873128 - 829
dBH4 concentration
at peak activity
106131
e[C]0.5 - Ki 34 - 28531 - 490

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

IVS10/IVS10

WT
aPeak PAH activity 371072658
Residual peak activity (in %) 5100
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)

PhenotypeResponsiveness

Tyr414Cys/Arg408Trp

WT
aPeak PAH activity 356072658
Residual peak activity (in %) 5100
bL-phenylalanine
concentration
at peak activity
301431
c[S]0.5 - Ki 87 - 528135 - 747
dBH4 concentration
at peak activity
139130
e[C]0.5 - Ki 33 - 40430 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Tyr414Cys/IVS12

WT
aPeak PAH activity 353781647
Residual peak activity (in %) 4100
bL-phenylalanine
concentration
at peak activity
291387
c[S]0.5 - Ki 79 - 523128 - 829
dBH4 concentration
at peak activity
112131
e[C]0.5 - Ki 53 - 31 - 490

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Thr380Met/Tyr414Cys

WT
aPeak PAH activity 1810572658
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

Tyr386Cys/IVS12

WT
aPeak PAH activity 156072658
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

H107P/Arg261Gln

WT
aPeak PAH activity 1443572658
Residual peak activity (in %) 20100
bL-phenylalanine
concentration
at peak activity
341431
c[S]0.5 - Ki 97 - 613135 - 747
dBH4 concentration
at peak activity
108130
e[C]0.5 - Ki 49 - 29530 - 294

Arg68Ser/IVS12

WT
aPeak PAH activity 592272658
Residual peak activity (in %) 8100
bL-phenylalanine
concentration
at peak activity
301431
c[S]0.5 - Ki 78 - 548135 - 747
dBH4 concentration
at peak activity
100130
e[C]0.5 - Ki 49 - 24730 - 294

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Ala104Asp/Ser349Pro

WT
aPeak PAH activity 375372658
Residual peak activity (in %) 5100
bL-phenylalanine
concentration
at peak activity
284431
c[S]0.5 - Ki 67 - 494135 - 747
dBH4 concentration
at peak activity
100130
e[C]0.5 - Ki 57 - 26730 - 294

Asp415Asn/IVS12

WT
aPeak PAH activity 965381647
Residual peak activity (in %) 12100
bL-phenylalanine
concentration
at peak activity
301387
c[S]0.5 - Ki 85 - 417128 - 829
dBH4 concentration
at peak activity
99131
e[C]0.5 - Ki 51 - 31 - 490

Clinical Data (data from BioPKU)

PhenotypeResponsiveness

Arg243Gln/IVS12

WT
aPeak PAH activity 129481647
Residual peak activity (in %) 2100
bL-phenylalanine
concentration
at peak activity
344387
c[S]0.5 - Ki 98 - 503128 - 829
dBH4 concentration
at peak activity
116131
e[C]0.5 - Ki 37 - 49731 - 490

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.