PAH activity landscapes

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	4769	72658
Residual peak activity (in %)	7	100
^bL-phenylalanine concentration at peak activity	351	431
^c[S]_0.5 - Ki	92 - 533	135 - 747
^dBH4 concentration at peak activity	146	130
^e[C]_0.5 - Ki	37 - 463	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Leu48Ser/Arg158Gln

		WT
^aPeak PAH activity	3041	72658
Residual peak activity (in %)	4	100
^bL-phenylalanine concentration at peak activity	330	431
^c[S]_0.5 - Ki	78 - 542	135 - 747
^dBH4 concentration at peak activity	200	130
^e[C]_0.5 - Ki	89 - 458	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Leu48Ser/Arg261Gln

		WT
^aPeak PAH activity	6229	72658
Residual peak activity (in %)	9	100
^bL-phenylalanine concentration at peak activity	501	431
^c[S]_0.5 - Ki	146 - 1164	135 - 747
^dBH4 concentration at peak activity	100	130
^e[C]_0.5 - Ki	31 - 302	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Leu48Ser/Arg408Trp

		WT
^aPeak PAH activity	2534	72658
Residual peak activity (in %)	4	100
^bL-phenylalanine concentration at peak activity	351	431
^c[S]_0.5 - Ki	90 - 543	135 - 747
^dBH4 concentration at peak activity	268	130
^e[C]_0.5 - Ki	33 - 432	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Leu48Ser/IVS10-11G>A

		WT
^aPeak PAH activity	5468	72658
Residual peak activity (in %)	8	100
^bL-phenylalanine concentration at peak activity	391	431
^c[S]_0.5 - Ki	103 - 556	135 - 747
^dBH4 concentration at peak activity	235	130
^e[C]_0.5 - Ki	32 - 432	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Leu48Ser/Tyr414Cys

		WT
^aPeak PAH activity	2815	72658
Residual peak activity (in %)	4	100
^bL-phenylalanine concentration at peak activity	341	431
^c[S]_0.5 - Ki	77 - 570	135 - 747
^dBH4 concentration at peak activity	98	130
^e[C]_0.5 - Ki	39 - 231	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Ile65Thr/IVS10-11G>A

		WT
^aPeak PAH activity	4978	72658
Residual peak activity (in %)	7	100
^bL-phenylalanine concentration at peak activity	441	431
^c[S]_0.5 - Ki	119 - 605	135 - 747
^dBH4 concentration at peak activity	409	130
^e[C]_0.5 - Ki	43 - 424	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Ile65Thr/IVS12+1G>A

		WT
^aPeak PAH activity	3343	81647
Residual peak activity (in %)	4	100
^bL-phenylalanine concentration at peak activity	404	387
^c[S]_0.5 - Ki	122 - 0	128 - 829
^dBH4 concentration at peak activity	123	131
^e[C]_0.5 - Ki	31 - 497	31 - 490

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Arg158Gln/Arg408Trp

		WT
^aPeak PAH activity	2470	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

Arg158Gln/Tyr414Cys

		WT
^aPeak PAH activity	1614	72658
Residual peak activity (in %)	2	100
^bL-phenylalanine concentration at peak activity	281	431
^c[S]_0.5 - Ki	72 - 520	135 - 747
^dBH4 concentration at peak activity	99	130
^e[C]_0.5 - Ki	54 - 235	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Arg241His/Arg408Trp

		WT
^aPeak PAH activity	2071	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

Val245Ala/Arg408Trp

		WT
^aPeak PAH activity	7486	72658
Residual peak activity (in %)	10	100
^bL-phenylalanine concentration at peak activity	391	431
^c[S]_0.5 - Ki	120 - 643	135 - 747
^dBH4 concentration at peak activity	157	130
^e[C]_0.5 - Ki	34 - 468	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Arg252Trp/Arg252Trp

		WT
^aPeak PAH activity	2699	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

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

		WT
^aPeak PAH activity	8031	72658
Residual peak activity (in %)	11	100
^bL-phenylalanine concentration at peak activity	762	431
^c[S]_0.5 - Ki	283 - 1314	135 - 747
^dBH4 concentration at peak activity	94	130
^e[C]_0.5 - Ki	28 - 249	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Arg261Gln/Arg408Trp

		WT
^aPeak PAH activity	4598	72658
Residual peak activity (in %)	6	100
^bL-phenylalanine concentration at peak activity	752	431
^c[S]_0.5 - Ki	252 - 1023	135 - 747
^dBH4 concentration at peak activity	99	130
^e[C]_0.5 - Ki	35 - 258	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Arg261Gln/Glu57Lys

		WT
^aPeak PAH activity	34075	81647
Residual peak activity (in %)	42	100
^bL-phenylalanine concentration at peak activity	371	387
^c[S]_0.5 - Ki	117 -	128 - 829
^dBH4 concentration at peak activity	145	131
^e[C]_0.5 - Ki	31 -	31 - 490

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Arg261Gln/IVS10-11G>A

		WT
^aPeak PAH activity	6013	72658
Residual peak activity (in %)	8	100
^bL-phenylalanine concentration at peak activity	802	431
^c[S]_0.5 - Ki	197 - 118	135 - 747
^dBH4 concentration at peak activity	149	130
^e[C]_0.5 - Ki	32 - 247	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Pro281Leu/Pro281Leu

		WT
^aPeak PAH activity	2265	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

Pro281Leu/Arg408Trp

		WT
^aPeak PAH activity	2297	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

Pro281Leu/IVS10-11G>A

		WT
^aPeak PAH activity	4163	72658
Residual peak activity (in %)	6	100
^bL-phenylalanine concentration at peak activity		431
^c[S]_0.5 - Ki	- 0	135 - 747
^dBH4 concentration at peak activity		130
^e[C]_0.5 - Ki	- 0	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Ile283Phe/Arg408Trp

		WT
^aPeak PAH activity	2534	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

Arg297His/Arg408Trp

		WT
^aPeak PAH activity	7162	72658
Residual peak activity (in %)	10	100
^bL-phenylalanine concentration at peak activity	882	431
^c[S]_0.5 - Ki	319 - 1938	135 - 747
^dBH4 concentration at peak activity	99	130
^e[C]_0.5 - Ki	29 - 219	30 - 294

Clinical Data (data from BioPKU)

Phenotype

Ala300Ser/Arg408Trp

		WT
^aPeak PAH activity	3819	72658
Residual peak activity (in %)	5	100
^bL-phenylalanine concentration at peak activity	391	431
^c[S]_0.5 - Ki	120 - 615	135 - 747
^dBH4 concentration at peak activity	135	130
^e[C]_0.5 - Ki	30 - 461	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Ala300Ser/IVS10-11G>A

		WT
^aPeak PAH activity	5011	72658
Residual peak activity (in %)	7	100
^bL-phenylalanine concentration at peak activity	431	431
^c[S]_0.5 - Ki	131 - 576	135 - 747
^dBH4 concentration at peak activity	219	130
^e[C]_0.5 - Ki	34 - 429	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Ala300Ser/Pro281Leu

		WT
^aPeak PAH activity	6529	72658
Residual peak activity (in %)	9	100
^bL-phenylalanine concentration at peak activity	361	431
^c[S]_0.5 - Ki	106 - 775	135 - 747
^dBH4 concentration at peak activity	110	130
^e[C]_0.5 - Ki	41 - 403	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Ile306Val/Arg408Trp

		WT
^aPeak PAH activity	4494	72658
Residual peak activity (in %)	6	100
^bL-phenylalanine concentration at peak activity	271	431
^c[S]_0.5 - Ki	64 - 513	135 - 747
^dBH4 concentration at peak activity	105	130
^e[C]_0.5 - Ki	52 - 298	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Leu348Val/Arg408Trp

		WT
^aPeak PAH activity	5700	72658
Residual peak activity (in %)	8	100
^bL-phenylalanine concentration at peak activity	511	431
^c[S]_0.5 - Ki	156 - 1046	135 - 747
^dBH4 concentration at peak activity	215	130
^e[C]_0.5 - Ki	31 - 331	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Val388Met/Arg408Trp

		WT
^aPeak PAH activity	5365	72658
Residual peak activity (in %)	7	100
^bL-phenylalanine concentration at peak activity	361	431
^c[S]_0.5 - Ki	112 - 730	135 - 747
^dBH4 concentration at peak activity	159	130
^e[C]_0.5 - Ki	32 - 371	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Glu390Gly/Arg408Trp

		WT
^aPeak PAH activity	6005	72658
Residual peak activity (in %)	8	100
^bL-phenylalanine concentration at peak activity	501	431
^c[S]_0.5 - Ki	150 - 770	135 - 747
^dBH4 concentration at peak activity	100	130
^e[C]_0.5 - Ki	30 - 288	30 - 294

Ala403Val/Arg408Trp

		WT
^aPeak PAH activity	6444	72658
Residual peak activity (in %)	9	100
^bL-phenylalanine concentration at peak activity	251	431
^c[S]_0.5 - Ki	52 - 510	135 - 747
^dBH4 concentration at peak activity	100	130
^e[C]_0.5 - Ki	44 - 226	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Arg408Trp/Arg408Trp

		WT
^aPeak PAH activity	1273	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

Arg408Trp/IVS10-11G>A

		WT
^aPeak PAH activity	2919	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

Arg408Trp/IVS12+1G>A

		WT
^aPeak PAH activity	2714	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

Arg408Trp/Phe402Leu

		WT
^aPeak PAH activity	3282	81647
Residual peak activity (in %)	4	100
^bL-phenylalanine concentration at peak activity	488	387
^c[S]_0.5 - Ki	150 - 873	128 - 829
^dBH4 concentration at peak activity	106	131
^e[C]_0.5 - Ki	34 - 285	31 - 490

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

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

		WT
^aPeak PAH activity	3710	72658
Residual peak activity (in %)	5	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

Tyr414Cys/Arg408Trp

		WT
^aPeak PAH activity	3560	72658
Residual peak activity (in %)	5	100
^bL-phenylalanine concentration at peak activity	301	431
^c[S]_0.5 - Ki	87 - 528	135 - 747
^dBH4 concentration at peak activity	139	130
^e[C]_0.5 - Ki	33 - 404	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Tyr414Cys/IVS12+1G>A

		WT
^aPeak PAH activity	3537	81647
Residual peak activity (in %)	4	100
^bL-phenylalanine concentration at peak activity	291	387
^c[S]_0.5 - Ki	79 - 523	128 - 829
^dBH4 concentration at peak activity	112	131
^e[C]_0.5 - Ki	53 -	31 - 490

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Thr380Met/Tyr414Cys

		WT
^aPeak PAH activity	18105	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

Tyr386Cys/IVS12+1G>A

		WT
^aPeak PAH activity	1560	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

H107P/Arg261Gln

		WT
^aPeak PAH activity	14435	72658
Residual peak activity (in %)	20	100
^bL-phenylalanine concentration at peak activity	341	431
^c[S]_0.5 - Ki	97 - 613	135 - 747
^dBH4 concentration at peak activity	108	130
^e[C]_0.5 - Ki	49 - 295	30 - 294

Arg68Ser/IVS12+1G>A

		WT
^aPeak PAH activity	5922	72658
Residual peak activity (in %)	8	100
^bL-phenylalanine concentration at peak activity	301	431
^c[S]_0.5 - Ki	78 - 548	135 - 747
^dBH4 concentration at peak activity	100	130
^e[C]_0.5 - Ki	49 - 247	30 - 294

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Ala104Asp/Ser349Pro

		WT
^aPeak PAH activity	3753	72658
Residual peak activity (in %)	5	100
^bL-phenylalanine concentration at peak activity	284	431
^c[S]_0.5 - Ki	67 - 494	135 - 747
^dBH4 concentration at peak activity	100	130
^e[C]_0.5 - Ki	57 - 267	30 - 294

Asp415Asn/IVS12+1G>A

		WT
^aPeak PAH activity	9653	81647
Residual peak activity (in %)	12	100
^bL-phenylalanine concentration at peak activity	301	387
^c[S]_0.5 - Ki	85 - 417	128 - 829
^dBH4 concentration at peak activity	99	131
^e[C]_0.5 - Ki	51 -	31 - 490

Clinical Data (data from BioPKU)

Phenotype	Responsiveness

Arg243Gln/IVS12+1G>A

		WT
^aPeak PAH activity	1294	81647
Residual peak activity (in %)	2	100
^bL-phenylalanine concentration at peak activity	344	387
^c[S]_0.5 - Ki	98 - 503	128 - 829
^dBH4 concentration at peak activity	116	131
^e[C]_0.5 - Ki	37 - 497	31 - 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.