Question

A heterotrophic cell encodes both the Pyruvate Carboxylase enzyme and the enzymes of the Glyoxylate Bypass. Contrast the reactions leading to oxaloacetate via both mechanisms, starting with PEP. In environments with low organic carbon, which reaction(s) would be favored for carrying out anaplerosis and why?

Answer 1

In many organisms, metabolite interconversion at the phosphoenolpyruvate (PEP)-pyruvate-oxaloacetate node involves a structurally entangled set of reactions that interconnects the major pathways of carbon metabolism and thus, is responsible for the distribution of the carbon flux among catabolism, anabolism and energy supply of the cell. While sugar catabolism proceeds mainly via oxidative or non-oxidative decarboxylation of pyruvate to acetyl-CoA, anaplerosis and the initial steps of gluconeogenesis are accomplished by C3- (PEP- and/or pyruvate-) carboxylation and C4- (oxaloacetate- and/or malate-) decarboxylation, respectively. In contrast to the relatively uniform central metabolic pathways in bacteria, the set of enzymes at the PEP-pyruvate-oxaloacetate node represents a surprising diversity of reactions. Variable combinations are used in different bacteria and the question of the significance of all these reactions for growth and for biotechnological fermentation processes arises. This review summarizes what is known about the enzymes and the metabolic fluxes at the PEP-pyruvate-oxaloacetate node in bacteria, with a particular focus on the C3-carboxylation and C4-decarboxylation reactions in Escherichia coli, Bacillus subtilis and Corynebacterium glutamicum. We discuss the activities of the enzymes, their regulation and their specific contribution to growth under a given condition or to biotechnological metabolite production. The present knowledge unequivocally reveals the PEP-pyruvate-oxaloacetate nodes of bacteria to be a fascinating target of metabolic engineering in order to achieve optimized metabolite production.

This reaction favoured to carrying out anaplerosis.

pyruvate + HCO3− + ATP ⟶ oxaloacetate + ADP + Pi + H2O

This reaction is catalysed by pyruvate carboxylase, an enzyme activated by acetyl-CoA, indicating a lack of oxaloacetate. It occurs in animal mitochondria. Most important anaplerotic reaction; depending on severity, deficiency causes lactic acidosis, severe psychomotor deficiency or death in infancy.Pyruvate can also be converted to L-malate, another intermediate, in a similar way.