Biochemistry

A (PEP)py Response

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Science  11 May 2012:
Vol. 336, Issue 6082, pp. 649-651
DOI: 10.1126/science.336.6082.649-d

Phosphoenolpyruvate (PEP), the final intermediate of glycolysis, is a central cellular metabolite. Besides its conversion to pyruvate by pyruvate kinase during glycolysis, in prokaryotes it is also the substrate for glucose phosphorylation (required for the import of glucose), and in some bacteria it is also converted to oxaloacetate by PEP carboxylase—an anapleurotic reaction that replenishes an intermediate in the tricarboxylic acid (TCA) cycle. Xu et al. found that as expected, depriving Escherichia coli of glucose resulted in a decrease in early glycolysis intermediates such as fructose-1,6,-biphosphate (FBP), but also observed the remarkable finding seen by others, that PEP increased at least 10-fold. A metabolic flux analysis showed that this was likely due to almost complete inhibition of PEP carboxylase. Although FBP is a known PEP carboxylase activator, on the basis of previously measured effects, the change in FBP concentration would not explain the reduction in PEP carboxylase activity. Rather, acetyl-CoA and aspartate enhanced the effect of FBP on PEP carboxylase activity, and modeling showed that this could explain the observed PEP accumulation. Metabolic data obtained with an FBP-insensitive mutant suggested that PEP accumulation is required for normal resumption of growth upon reexposure to glucose. Thus, the anaplerotic reaction is switched on and off through sensitive allosteric regulation of PEP carboxylase, enabling bacteria to rapidly adapt to changing environmental conditions.

Nat. Chem. Biol. 8, 10.1038/nchembio.941 (2012).

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