Metabolic regulation substrate cycles

E.A. Newsholme and B. Crabtree, Substrate cycles in metabolic regulation and in heat generation, Biochem. Soc. Symp., 1976, 43, 61-109. 

Substrate cycling also provides a means of increasing the sensitivity and speed of metabolic regulation. The increased rate of glycolysis in response to a need for ATP for muscle contraction would imply a more or less instantaneous 1000-fold increase in phosphofructokinase activity if phosphofructokinase were inactive and fructose 1,6-bisphosphatase active. If there is moderate activity of phosphofructokinase, but greater activity of fructose 1,6-bisphosphatase, so that the metabolic flux is in the direction of gluconeogenesis, then a more modest increase in phosphofructokinase activity and decrease in fructose 1,6-bisphosphatase activity will achieve the same reversal of the direction of flux. 

For type 3 processes, growth and metabolic activity reach a maximum early in the batch process cycle (Figure 3.1) and it is not until a later stage, when oxidative activity is low, that maximum desired product formation occurs. The stoichiometric descriptions for both type 3 and 4 processes depend upon the particular substrates and products involved. In the main, product formation in these processes is completely uncoupled from cell growth and dictated by kinetic regulation and activity of cells. 

The tightly regulated pathway specifying aromatic amino acid biosynthesis within the plastid compartment implies maintenance of an amino acid pool to mediate regulation. Thus, we have concluded that loss to the cytoplasm of aromatic amino acids synthesized in the chloroplast compartment is unlikely (13). Yet a source of aromatic amino acids is needed in the cytosol to support protein synthesis. Furthermore, since the enzyme systems of the general phenylpropanoid pathway and its specialized branches of secondary metabolism are located in the cytosol (17), aromatic amino acids (especially L-phenylalanine) are also required in the cytosol as initial substrates for secondary metabolism. The simplest possibility would be that a second, complete pathway of aromatic amino acid biosynthesis exists in the cytosol. Ample precedent has been established for duplicate, major biochemical pathways (glycolysis and oxidative pentose phosphate cycle) of higher plants that are separated from one another in the plastid and cytosolic compartments (18). Evidence to support the hypothesis for a cytosolic pathway (1,13) and the various approaches underway to prove or disprove the dual-pathway hypothesis are summarized in this paper. 

Oxidation of Other Substrates by the TCA Cycle The TCA Cycle Activity Is Regulated at Metabolic Branchpoints... 

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