8. P R O T E I N M E T A B O L I S M IN C E L L LINES
295
in vivo controls, which are no less real for the fact that they are as
yet undefined. It is of interest in this connexion that only a few instances
of the phenomena of enzyme repression and end-product inhibition,
operative in the control of many cellular synthetic processes in microorganisms, have been demonstrated up to now in dispersed mammalian
cells. One such instance is the apparent repression of the enzyme
responsible for glutamine synthesis in cells grown in the presence of
glutamine (DeMars, 1958). More recently, repression by arginine of
the enzymes which effect its synthesis from citrulline has been demonstrated in several cell lines with the aid of extremely sensitive enzyme
assays (Schimke, 1962). O n the other hand, the rate of formation in
growing cells of serine, alanine, glycine, and citrulline has been found to
be unaffected by provision of the end product in concentrations up to
2 mM, approximately 5-100 times the concentration which would
otherwise appear in the medium.
It is of obvious importance to determine by appropriately sensitive
techniques whether the examples of enzyme repression cited above
are representative of numerous similar control mechanisms in cultured
cells, or whether they are merely isolated exceptional cases. Equally
important is determination of the degree to which these or similar
phenomena are operative in vivo, or in organized surviving tissue, as
distinct from dispersed growing cells.
R E F E R E N C E S
Buonassisi, V . , Sato, G . and Cohen, A . (1962). H o r m o n e producing cultures o f
adrenal and pituitary tumor origin. Fed. Proc. 21, 188.
DeMars, R . I. (1958). T h e inhibition b y glutamine o f glutamyl transferase formation
in cultures o f human cells. Biochim. biophys. Acta 27, 435.
Eagle, H . (1959). A m i n o acid metabolism in mammalian cell cultures. Science 130,
432.
Eagle, H . (1960). T h e sustained growth o f human and animal cells in a protein-free
environment. Proc. nat. Acad. Sci. f Wash. 46, 427.
Eagle, H . and Piez, K . A . (1960). T h e utilization o f proteins b y cultured human cells.
J. biol. Chem. 235, 1095.
Eagle, H . and Piez, K . A . (1962a). T h e population-dependent requirement b y
cultured mammalian cells for metabolites which they can synthesize. J. exp. Med.
116, 29.
Eagle, H . and Piez, K . A . (1962b). A m i n o - a c i d pools, protein synthesis and protein
turnover in human cell cultures. In " A m i n o A c i d Pools" (J. T . Holden, e d . ) ,
p . 694. Elsevier, A m s t e r d a m - L o n d o n - N e w York.
Eagle, H . , Piez, K . A . , Fleischman, R . and O y a m a , V . I. (1959). Protein turnover in
mammalian cell cultures. J. biol. Chem. 234, 592.
Eagle, H . , Piez, K . A . and Levy, M . (1961). T h e intracellular amino acid concentrations required for protein synthesis in cultured human cells. J. biol. Chem. 236,
2039.
295
in vivo controls, which are no less real for the fact that they are as
yet undefined. It is of interest in this connexion that only a few instances
of the phenomena of enzyme repression and end-product inhibition,
operative in the control of many cellular synthetic processes in microorganisms, have been demonstrated up to now in dispersed mammalian
cells. One such instance is the apparent repression of the enzyme
responsible for glutamine synthesis in cells grown in the presence of
glutamine (DeMars, 1958). More recently, repression by arginine of
the enzymes which effect its synthesis from citrulline has been demonstrated in several cell lines with the aid of extremely sensitive enzyme
assays (Schimke, 1962). O n the other hand, the rate of formation in
growing cells of serine, alanine, glycine, and citrulline has been found to
be unaffected by provision of the end product in concentrations up to
2 mM, approximately 5-100 times the concentration which would
otherwise appear in the medium.
It is of obvious importance to determine by appropriately sensitive
techniques whether the examples of enzyme repression cited above
are representative of numerous similar control mechanisms in cultured
cells, or whether they are merely isolated exceptional cases. Equally
important is determination of the degree to which these or similar
phenomena are operative in vivo, or in organized surviving tissue, as
distinct from dispersed growing cells.
R E F E R E N C E S
Buonassisi, V . , Sato, G . and Cohen, A . (1962). H o r m o n e producing cultures o f
adrenal and pituitary tumor origin. Fed. Proc. 21, 188.
DeMars, R . I. (1958). T h e inhibition b y glutamine o f glutamyl transferase formation
in cultures o f human cells. Biochim. biophys. Acta 27, 435.
Eagle, H . (1959). A m i n o acid metabolism in mammalian cell cultures. Science 130,
432.
Eagle, H . (1960). T h e sustained growth o f human and animal cells in a protein-free
environment. Proc. nat. Acad. Sci. f Wash. 46, 427.
Eagle, H . and Piez, K . A . (1960). T h e utilization o f proteins b y cultured human cells.
J. biol. Chem. 235, 1095.
Eagle, H . and Piez, K . A . (1962a). T h e population-dependent requirement b y
cultured mammalian cells for metabolites which they can synthesize. J. exp. Med.
116, 29.
Eagle, H . and Piez, K . A . (1962b). A m i n o - a c i d pools, protein synthesis and protein
turnover in human cell cultures. In " A m i n o A c i d Pools" (J. T . Holden, e d . ) ,
p . 694. Elsevier, A m s t e r d a m - L o n d o n - N e w York.
Eagle, H . , Piez, K . A . , Fleischman, R . and O y a m a , V . I. (1959). Protein turnover in
mammalian cell cultures. J. biol. Chem. 234, 592.
Eagle, H . , Piez, K . A . and Levy, M . (1961). T h e intracellular amino acid concentrations required for protein synthesis in cultured human cells. J. biol. Chem. 236,
2039.