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
255
also utilize a significant amount of energy (Swann, 1953), although the
precise requirements are not known.
Another more general relationship which has been suggested is that
aerobic pathways are essential for specialized functions in differentiated
cells, whereas the energy for the fundamental synthetic reactions
involved in undifferentiated growth can be derived entirely from
glycolysis. Some aspects of this topic have already been discussed and
only those observations which relate to the dependence on aerobic pathways of the three functions mentioned will be considered.
1. Dependence of Amino Acid Synthesis on Aerobic Pathways
In a minimum medium, such as Eagle's (1959) in which only the
essential amino acids are present, the non-essential amino acids must be
formed by transamination, and this requires that the necessary carbon
skeletons be available. Certain of them, e.g. oxaloacetate or fumarate, in
the formation of aspartic acid, or oxoglutarate, in the formation of
glutamic acid, are intermediates in the Krebs cycle. Consequently, some
oxidation of pyruvic acid is essential in these circumstances and it can
be stated with certainty, therefore, that continuous growth in a medium
which is not supplied with either a complete amino-acid supplement or
these Krebs cycle intermediates must be dependent on oxidative pathways.
2. Dependence of Nucleic Acid Synthesis on Aerobic Pathways
Cultured animal cells are able to synthesize nucleotides and nucleic
acids from glucose and certain amino acids (Horecker, Domagk and
Hiatt, 1958; Hiatt, 1957; Thomson, Paul and Davidson, 1958). These
reactions involve a number of dehydrogenations, e.g. in the oxidative
conversion of glucose to pentoses via the pentose-phosphate shunt. In
the normal course of events, therefore, electron-transport mechanisms
linked to a hydrogen acceptor are essential for long-term survival
unless a rather complete supplement of nucleosides is provided in the
medium. Only a few synthetic media meet this requirement.
It has generally been found that cell strains will not grow indefinitely
in anaerobic conditions in the defined media currently available. This
observation is at variance with some apparently well-substantiated
reports in the literature that certain fibroblastic cells in primary explants will grow in completely anaerobic conditions (Burrows, 1921,
1924; Harris, 1956; Laser, 1933; Medawar, 1947; Meier, 1931;
Warburg, 1930; Warburg and Kubowitz, 1927). Accepting the reliability of these reports (and there may be a question in some instances
about the adequacy of the anaerobic conditions) there would seem to be
four possible explanations: (a) either no synthesis of new cellular
255
also utilize a significant amount of energy (Swann, 1953), although the
precise requirements are not known.
Another more general relationship which has been suggested is that
aerobic pathways are essential for specialized functions in differentiated
cells, whereas the energy for the fundamental synthetic reactions
involved in undifferentiated growth can be derived entirely from
glycolysis. Some aspects of this topic have already been discussed and
only those observations which relate to the dependence on aerobic pathways of the three functions mentioned will be considered.
1. Dependence of Amino Acid Synthesis on Aerobic Pathways
In a minimum medium, such as Eagle's (1959) in which only the
essential amino acids are present, the non-essential amino acids must be
formed by transamination, and this requires that the necessary carbon
skeletons be available. Certain of them, e.g. oxaloacetate or fumarate, in
the formation of aspartic acid, or oxoglutarate, in the formation of
glutamic acid, are intermediates in the Krebs cycle. Consequently, some
oxidation of pyruvic acid is essential in these circumstances and it can
be stated with certainty, therefore, that continuous growth in a medium
which is not supplied with either a complete amino-acid supplement or
these Krebs cycle intermediates must be dependent on oxidative pathways.
2. Dependence of Nucleic Acid Synthesis on Aerobic Pathways
Cultured animal cells are able to synthesize nucleotides and nucleic
acids from glucose and certain amino acids (Horecker, Domagk and
Hiatt, 1958; Hiatt, 1957; Thomson, Paul and Davidson, 1958). These
reactions involve a number of dehydrogenations, e.g. in the oxidative
conversion of glucose to pentoses via the pentose-phosphate shunt. In
the normal course of events, therefore, electron-transport mechanisms
linked to a hydrogen acceptor are essential for long-term survival
unless a rather complete supplement of nucleosides is provided in the
medium. Only a few synthetic media meet this requirement.
It has generally been found that cell strains will not grow indefinitely
in anaerobic conditions in the defined media currently available. This
observation is at variance with some apparently well-substantiated
reports in the literature that certain fibroblastic cells in primary explants will grow in completely anaerobic conditions (Burrows, 1921,
1924; Harris, 1956; Laser, 1933; Medawar, 1947; Meier, 1931;
Warburg, 1930; Warburg and Kubowitz, 1927). Accepting the reliability of these reports (and there may be a question in some instances
about the adequacy of the anaerobic conditions) there would seem to be
four possible explanations: (a) either no synthesis of new cellular