250
J O H N P A U L
aspartic acid, glutamic acid, alanine, serine, glycine and proline in the
tissue protein of chick heart fibroblasts. Similar results were reported by
Harris and Jahnz (1957, 1958) who also found a trace of activity in
threonine.
The synthesis of nucleosides requires the formation of phosphoribosyl
pyrophosphate from glucose, and since cultured cells can grow in the
absence of preformed bases when glucose is the sole carbohydrate
source there is no doubt that the enzymes capable of performing these
conversions are present and fully functional.
B. DO C U L T U R E D CELLS H A V E A C H A R A C T E R I S T I C
M E T A B O L I C P A T T E R N ?
The observations described above indicate quite clearly that all the
common carbohydrate pathways are present in most cultured cells.
This would at first seem to contradict the prevalent idea that cultured
cells always revert to a glycolytic type of carbohydrate metabolism.
There is, however, no doubt that within a day or two of being explanted
the amount of lactic acid produced by tissue cultures increases greatly
(Gershanovitch, Agol, Etingof and Dzagurov, 1958; Paul and Pearson,
1957a, b ; Suschny, Kellner, Broda, Figdor and Riicker, 1958; Warburg,
Gawehn, Geissler, Schroder, Gewitz and Volker, 1958) and that the
respiration of some tissues may at the same time diminish. In embryonic
tissues Warburg (1930) attributed this latter phenomenon to irreversible
damage. The question arises whether the reversion to a glycolytic
pattern is due to a loss of some properties of the intact tissue or whether
it is due to the direct effect of the environment. The evidence concerning
the first point is inconclusive. Agol et al. (1959) and Turner (1962) have
shown that cultured cells display disturbances of the cytochromes and
succinic dehydrogenase. Since Adebonojo, Bensch and King (1961)
have produced similar changes by maintaining cells under nitrogen
these may be secondary to accidental environmental factors rather than
to intrinsic differences resulting from tissue disruption. On the other
hand it has been amply demonstrated that aerobic glycolysis can be
readily influenced by environmental factors (Danes and Paul, 1961a, b)
and that the glycolytic pattern of cultured cells can be converted back
to an aerobic pattern in appropriate circumstances ( M . Harris, 1958;
Munyon and Merchant, 1959; Paul and Pearson, 1957a). There seems
little doubt therefore that the environment plays a very large part in the
establishment of a glycolytic pattern of carbohydrate metabolism in
vitro (Paul, 1959, 1961; Paul, Danes, Struthers, Withers and Richfeld,
1960) .
It has to be remembered that the tissue culture environment may be
J O H N P A U L
aspartic acid, glutamic acid, alanine, serine, glycine and proline in the
tissue protein of chick heart fibroblasts. Similar results were reported by
Harris and Jahnz (1957, 1958) who also found a trace of activity in
threonine.
The synthesis of nucleosides requires the formation of phosphoribosyl
pyrophosphate from glucose, and since cultured cells can grow in the
absence of preformed bases when glucose is the sole carbohydrate
source there is no doubt that the enzymes capable of performing these
conversions are present and fully functional.
B. DO C U L T U R E D CELLS H A V E A C H A R A C T E R I S T I C
M E T A B O L I C P A T T E R N ?
The observations described above indicate quite clearly that all the
common carbohydrate pathways are present in most cultured cells.
This would at first seem to contradict the prevalent idea that cultured
cells always revert to a glycolytic type of carbohydrate metabolism.
There is, however, no doubt that within a day or two of being explanted
the amount of lactic acid produced by tissue cultures increases greatly
(Gershanovitch, Agol, Etingof and Dzagurov, 1958; Paul and Pearson,
1957a, b ; Suschny, Kellner, Broda, Figdor and Riicker, 1958; Warburg,
Gawehn, Geissler, Schroder, Gewitz and Volker, 1958) and that the
respiration of some tissues may at the same time diminish. In embryonic
tissues Warburg (1930) attributed this latter phenomenon to irreversible
damage. The question arises whether the reversion to a glycolytic
pattern is due to a loss of some properties of the intact tissue or whether
it is due to the direct effect of the environment. The evidence concerning
the first point is inconclusive. Agol et al. (1959) and Turner (1962) have
shown that cultured cells display disturbances of the cytochromes and
succinic dehydrogenase. Since Adebonojo, Bensch and King (1961)
have produced similar changes by maintaining cells under nitrogen
these may be secondary to accidental environmental factors rather than
to intrinsic differences resulting from tissue disruption. On the other
hand it has been amply demonstrated that aerobic glycolysis can be
readily influenced by environmental factors (Danes and Paul, 1961a, b)
and that the glycolytic pattern of cultured cells can be converted back
to an aerobic pattern in appropriate circumstances ( M . Harris, 1958;
Munyon and Merchant, 1959; Paul and Pearson, 1957a). There seems
little doubt therefore that the environment plays a very large part in the
establishment of a glycolytic pattern of carbohydrate metabolism in
vitro (Paul, 1959, 1961; Paul, Danes, Struthers, Withers and Richfeld,
1960) .
It has to be remembered that the tissue culture environment may be