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Cultured rat hepatoma cells, H4-II-E-C3, are known to possess a phenylananine hydroxylating system which is sufficient to enable them to grow in tyrosine-depleted medium. Using standard procedures of auxotroph enrichment with this cell line, we have isolated tyrosine auxotrophs for the first time. We report in this paper the class of auxotrophs with (a) reduced (15-64% of wild type) or (b) absent activity of phenylalanine hydroxylase, an enzymic component of the phenylalanine hydroxylating system. This class of auxotroph presumably contains either lower (a) [or zero (b)] levels of normal phenylalanine hydroxylase protein than wild type, or mutant phenylalanine hydroxylase protein with lowered (or zero) activity. The two subgroups of auxotrophs (a) and (b) differ from each other in their revertibility and their growth behavior in the tyrosine-free medium. Over a 12-month period of testing, the auxotrophs have been highly stable with respect to their phenylalanine hydroxylase activity and growth phenotype in tyrosine-free medium. Such auxotrophs should facilitate genetic and biochemical study of the genes controlling the phenylalanine hydroxylation system and the study of phenylketonuria.
K H Choo, and
R G Cotton
December 1981,
Proceedings of the National Academy of Sciences of the United States of America,
K H Choo, and
R G Cotton
January 1976,
Biochemical and biophysical research communications,
K H Choo, and
R G Cotton
January 1983,
Somatic cell genetics,
K H Choo, and
R G Cotton
June 1974,
The Biochemical journal,
K H Choo, and
R G Cotton
November 1976,
The Journal of biological chemistry,
K H Choo, and
R G Cotton
April 1969,
Journal of cellular physiology,
K H Choo, and
R G Cotton
August 1991,
The Journal of biological chemistry,
K H Choo, and
R G Cotton
June 1989,
Biochemistry and cell biology = Biochimie et biologie cellulaire,
K H Choo, and
R G Cotton
October 1979,
The Journal of biological chemistry,
K H Choo, and
R G Cotton
August 1979,
Proceedings of the National Academy of Sciences of the United States of America,
