Missense mutations in the phenylalanine hydroxylase gene (PAH) can cause accelerated proteolytic turnover of PAH enzyme: A mechanism underlying phenylketonuria

Journal of Inherited Metabolic Disease

Volumn 22, Issue 3, 1999, Pages 208-212

  Waters, P J ^a,c   Parniak, M A ^b   Akerman, B R ^a   Jones, A O ^a   Scriver, C R ^a  

^a RESEARCH INSTITUTE OF THE MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^b MCGILL UNIVERSITY   (Canada)

^c MONTREAL CHILDREN S HOSPITAL   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

PHENYLALANINE 4 MONOOXYGENASE;

CELL LYSATE; CONFERENCE PAPER; ENZYME ACTIVITY; ENZYME DEGRADATION; ENZYME METABOLISM; ENZYME STABILITY; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; MAMMAL CELL; MISSENSE MUTATION; PATHOGENESIS; PHENYLKETONURIA; PROTEIN DEGRADATION;

HUMANS; MUTATION, MISSENSE; PHENYLALANINE HYDROXYLASE; PHENYLKETONURIAS;

EID: 0033000446     PISSN: 01418955     EISSN: None     Source Type: Journal    
DOI: 10.1023/A:1005533825980     Document Type: Conference Paper

References (14)

1. Corydon TJ, Bross P, Jensen TG, et al (1998) Rapid degradation of short chain acyl-CoA dehydrogenase variants with temperature-sensitive folding defects occurs after import into mitochondria. J Biol Chem 273: 13065-13071.
2. Craiu A, Gaczynska M, Akopian T, et al (1997) Lactacystin and clasto-lactacystin β-lactone modify multiple proteasome β-subunits and inhibit intracellular protein degradation and major histocompatability complex class I antigen presentation. J Biol Chem 272: 13437-13445.
3. 1-antitrypsin Z, in the endoplasmic reticulum requires proteasome activity. J Biol Chem 271: 22791-22795.
4. Doskeland AP, Flatmark T (1996) Recombinant human phenylalanine hydroxylase is a substrate for the ubiquitin-conjugating enzyme system. Biochem J 319: 941-945.
5. Eiken HG, Knappskog PM, Apold J, Flatmark T (1996) PKU mutation G46S is associated with increased aggregation and degradation of the phenylalanine hydroxylase enzyme. Hum Mut at 7: 228-238.
6. Guldberg P, Rey F, Zschocke J, et al (1998) A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype. An J Hum Genet 63: 71-79.
7. Kayaalp E, Treacy EP, Waters PJ, Byck S, Nowacki P, Scriver CR (1997) Human phenylalanine hydroxylase mutations and hyperphenylalaninemia phenotypes: a metanalysis of genotype-phenotype correlations. Am J Hum Genet 61: 1309-1317.
8. Knappskog PM, Eiken HG, Martinez A, Bruland O, Apold J, Flatmark T (1996) A PKU mutation (D143G) associated with an apparent high residual enzyme activity: expression of a kinetic variant form of phenylalanine hydroxylase in three different systems. Hum Mutat 8: 236-246.
9. Lai K, Langley SD, Dembure PP, Hjelm LN, Elsas LJ II (1998) Duarte allele impairs biostability of galactose-1-phosphate uridyltransferase in human lymphoblasts. Hum Mutat 11: 28-38.
10. Meerovitch K, Wing S, Goltzmann D (1997) Preproparathyroid hormone-related protein, a secreted peptide, is a substrate for the ubiquitin proteolytic system. J Biol Chem 272: 6706-6713.
11. Nowacki P, Byck S, Prevost L, Scriver CR (1998) PAH Mutation Analysis Consortium Database: 1997. Prototype for relational locus-specific mutation databases. Nucleic Acids Res 26: 220-225.
12. Varshavsky A (1997) The ubiquitin system. Trends Biochem Sci 22: 383-387.
13. Waters PJ, Parniak MA, Nowacki P, Scriver CR (1998a) In vitro expression analysis of mutations in phenylalanine hydroxylase: linking genotype to phenotype and structure to function. Hum Mutat 11: 4-17.
14. Waters PJ, Parniak MA, Hewson AS, Scriver CR (1998b) Alterations in protein aggregation and degradation due to mild and severe missense mutations (A104D, R157N) in the human phenylalanine hydroxylase gene (PAH). Hum Mutat 12: 344-354.