Biochemical Defect of the hph‐1 Mouse Mutant Is a Deficiency in GTP‐Cyclohydrolase Activity

J. David McDonald, Richard G.H. Cotton, Ian Jennings, Fred D. Ledley, Savio L.C. Woo, Vernon C. Bode

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A hyperphenylalaninemic mouse mutant, hph‐1, has been identified in the progeny of mice treated with the mutagen ethylnitrosourea. Phenylalanine hydroxylase activity levels in mutant liver lysates are reduced relative to normal, but correction for the amount of enzyme protein present demonstrates that the specific activity of this enzyme is normal in mutant mice. Quinonoid‐dihydropteridine reductase activity is also normal. GTP‐cyclohydrolase activity levels are essentially absent early in life and greatly diminished later in life. This finding has significant implications for the study of catecholamine neurotransmitter synthesis because GTP‐cyclohydrolase catalyzes an important step in the de novo synthesis of tetrahydrobiopterin, an enzyme cofactor required for the synthesis of 3,4‐dihydroxyphenylalanine (DOPA) and serotonin.

Original languageEnglish
Pages (from-to)655-657
Number of pages3
JournalJournal of Neurochemistry
Issue number2
Publication statusPublished - 1 Jan 1988
Externally publishedYes


  • Ethylnitrosourea mutagenesis
  • GTP‐cyclohydrolase.
  • Hyperphenylalaninemia
  • Phenylalanine hydroxylase
  • Quinonoid‐dihydropteridine reductase
  • Tetrahydrobiopterin

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