7. C A R B O H Y D R A T E A N D E N E R G Y M E T A B O L I S M
241
precursors. Cells consume energy both in synthesizing extracellular
substances and in replicating their own macromolecules. The former
cannot be discounted in cell cultures because there is ample evidence
that cultured cells can synthesize extracellular mucopolysaccharides
and proteins (Daniel, Dingle and Webb, 1960; Grossfeld, 1957;
Grossfeld, Meyer, Goodman and Linker, 1957; Jackson and Smith,
1957; H. Kuwabara, 1959). The synthesis of extracellular materials has
not been studied quantitatively in the cases which will be discussed, but
again it must be kept in mind that there may be some extra requirement
of energy for this purpose.
Fortunately there is no shortage of data about the chemical composition of several cultured cells. Knowing this and making some justifiable
assumptions it is possible to arrive at an approximate estimate of the
minimum amount of energy required for the synthesis of a single cell.
Calculations relating to three cell-types, one very small (L 5178), one
medium-sized (L-strain, mouse fibroblast) and one fairly large (HeLa
cell, human carcinoma) are presented in Table I. The analytical
figures are averages derived from several analyses (6 for L5178, 12 for
HeLa and 25 for L ) . The assumptions involved in calculating the
number of A T P molecules consumed per monomer are as follows: (a)
7 A T P are synthesized in the formation of 1 CoA from glucose and
approximately 5 are consumed in the incorporation of an acetic acid
monomer into a fatty acid, giving a net gain of about 2 A T P per monomer; (b) for the synthesis of each peptide bond 2 A T P are consumed in
the formation of the aminoacyl adenylate and another (actually G T P )
in the transfer to the polypeptide chain; (c) the figure for nucleic acids
is based on the assumption that phosphoribosyl pyrophosphate is
derived from glucose and that the formation of formyl tetrahydrofolic
acid is predominantly by non-reducing reactions. There is then an
average net gain of about 2 A T P per mononucleotide unit assuming
equimolecular amounts of purines and pyrimidines. 2 A T P are required for formation of triphosphates prior to polymerization; (d)
2 A T P are required for polymerization of glucose via UDP-glucose.
These represent known A T P requirements and are probably minimum
values. The turnover values quoted in the table for protein and nucleic
acids are experimental values quoted in studies on cultured cells (Eagle,
Piez, Fleischman and Oyama, 1959; Harris and Watts, 1958; Jordan,
Miller and Peters, 1959; Watts and Harris, 1959) with the exception of
the figure in parentheses for turnover of nucleic acids. This represents
the A T P which would be required if the "messenger R N A " template
served only once and was then broken down to nucleotides (Brenner,
Jacob and Meselson, 1961). Assuming a coding ratio of 3:1 this would
require that three phosphate diester linkages be formed in messenger
241
precursors. Cells consume energy both in synthesizing extracellular
substances and in replicating their own macromolecules. The former
cannot be discounted in cell cultures because there is ample evidence
that cultured cells can synthesize extracellular mucopolysaccharides
and proteins (Daniel, Dingle and Webb, 1960; Grossfeld, 1957;
Grossfeld, Meyer, Goodman and Linker, 1957; Jackson and Smith,
1957; H. Kuwabara, 1959). The synthesis of extracellular materials has
not been studied quantitatively in the cases which will be discussed, but
again it must be kept in mind that there may be some extra requirement
of energy for this purpose.
Fortunately there is no shortage of data about the chemical composition of several cultured cells. Knowing this and making some justifiable
assumptions it is possible to arrive at an approximate estimate of the
minimum amount of energy required for the synthesis of a single cell.
Calculations relating to three cell-types, one very small (L 5178), one
medium-sized (L-strain, mouse fibroblast) and one fairly large (HeLa
cell, human carcinoma) are presented in Table I. The analytical
figures are averages derived from several analyses (6 for L5178, 12 for
HeLa and 25 for L ) . The assumptions involved in calculating the
number of A T P molecules consumed per monomer are as follows: (a)
7 A T P are synthesized in the formation of 1 CoA from glucose and
approximately 5 are consumed in the incorporation of an acetic acid
monomer into a fatty acid, giving a net gain of about 2 A T P per monomer; (b) for the synthesis of each peptide bond 2 A T P are consumed in
the formation of the aminoacyl adenylate and another (actually G T P )
in the transfer to the polypeptide chain; (c) the figure for nucleic acids
is based on the assumption that phosphoribosyl pyrophosphate is
derived from glucose and that the formation of formyl tetrahydrofolic
acid is predominantly by non-reducing reactions. There is then an
average net gain of about 2 A T P per mononucleotide unit assuming
equimolecular amounts of purines and pyrimidines. 2 A T P are required for formation of triphosphates prior to polymerization; (d)
2 A T P are required for polymerization of glucose via UDP-glucose.
These represent known A T P requirements and are probably minimum
values. The turnover values quoted in the table for protein and nucleic
acids are experimental values quoted in studies on cultured cells (Eagle,
Piez, Fleischman and Oyama, 1959; Harris and Watts, 1958; Jordan,
Miller and Peters, 1959; Watts and Harris, 1959) with the exception of
the figure in parentheses for turnover of nucleic acids. This represents
the A T P which would be required if the "messenger R N A " template
served only once and was then broken down to nucleotides (Brenner,
Jacob and Meselson, 1961). Assuming a coding ratio of 3:1 this would
require that three phosphate diester linkages be formed in messenger