Glycolysis metabolic control

B. Chance, D. Garfinkel, J. Higgins, and B. Hess, Metabolic control mechanisms A solution for the equations representing interaction between glycolysis and respiration in ascites tumor cells. 

A large intracellular pool of a) ions (caused by a negative effect of severe limitation of b) on protein turnover) and an increased respiratory activity, which in part is not coupled to c) synthesis, stimulates metabolic flux throu glycolysis without significant metabolic control. This, togettier with d) pyruvate carboxylase and the peculiarities in the operation of the TCA-cyde, results in elevat cellular concentrations of e>. This in turn enhances dtric add accumulation by inhibiting i) dehydrogenase. 

Figure 5.8. The Warburg anaerobic glycolytic effect. Because of the early growth effects of foci and small neoplasms, the transformed cells separate from the local blood supply and become more anoxic as they expand. Cells at the lead edge show the most effects of O2 deprivation, and this deprivation switches metabolism control in these distal cells from the 38 ATP-rich TCA cycle to glycolysis (only 2 ATPs) and fermentation to lactic acid.

Now that we know something about the effects of hormones in triggering responses within the cell, we can return to and expand on some earlier points about metabolic control. In Section 18.3, we discussed some points about control mechanisms in carbohydrate metabolism. We saw at that time how glycolysis and gluconeogenesis can be regulated and how glycogen synthesis and breakdown can respond to the body s needs. Phosphorylation and dephosphorylation of the appropriate enzymes played a large role there, and that whole scheme is subject to hormonal action. 

Situated as it is between glycolysis and the electron transport chain, the TCA cycle must be carefully controlled by the ceil. If the cycle were permitted to run unchecked, large amounts of metabolic energy could be wasted in overproduction of reduced coenzymes and ATP conversely, if it ran too slowly, ATP would not be produced rapidly enough to satisfy the needs of the cell. Also, as just seen, the TCA cycle is an important source of precursors for biosynthetic processes and must be able to provide them as needed. 

---