Cell growth in ‘ornithine-medium’ requires the expression of two liver-specific genes, those for ornithine transcarbamoylase (OTC) and carbamoyl phosphate synthetase I (CPS-I). CPS-II appears unable to replace CPS-I in this system. The need for N-acetylglutamate (to activate CPS-I) can be met, at least in part, by providing it in the medium. The other gene products involved in arginine biosynthesis are probably all ubiquitous (i.e. not tissue-specific). In an attempt to study the factors responsible for the expression of liver-specific genes, variant hepatomas are isolated that have lost the ability to grow in ornithine-medium. Two classes of ‘orn-’ variants are identified: unstable variants that require dexamethasone for adequate CPS-I production, and ‘stable’ variants that have lost many liver-specific traits. Studies on one stable variant show that it can revert (though rarely), and that it regains its various liver-specific traits in a non-coordinate fashion.
Molecular Characterization of Carbamoyl-Phosphate Synthetase (CPS1) Deficiency Using Human Recombinant CPS1 as a Key Tool
