Correction: Phosphoglycolate phosphatase is a metabolic proofreading enzyme essential for cellular function in Plasmodium berghei.

Abstract

During copy editing, an error was introduced in a column label in Table 1. The label of the last column should be k cat /K m. This error has now been corrected and does not affect the results and conclusions of this work.

The physical basis and practical consequences of biological promiscuity

“…Loss of phosphoglycolate phosphatase in yeast and other human cells perturbs metabolism [126], but the cells are viable. In contrast, the enzyme is essential in Plasmodium berghei [129].…”

“…Hydrolysis of 1,4-bisphosphoerythronate by an unknown mechanism (possibly a promiscuous enzyme) produces 4-phosphoerythronate, a potent inhibitor of 6-phosphogluconate dehydrogenase in humans, yeast [126,128] and Bacillus subtilis [128]. Inhibition of 6-phosphogluconate dehydrogenase leads to elevated levels of its substrate, 6-phosphogluconate, which in turn inhibits phosphoglucose isomerase, decreasing flux through glycolysis and impairing or even abolishing growth [128,129]. Phosphoglycolate phosphatase (a polyspecific enzyme named for its ability to hydrolyze a by-product of oxidative damage to DNA) hydrolyzes 4-phosphoerythronate in human and yeast cells with a very respectable k cat /K M of >10 4 M −1 s −1 .…”

“…Consequently, inhibition of PFK-2 by 2-phospholactate perturbs glucose metabolism. Phosphoglycolate phosphatase efficiently hydrolyses 2-phospholactate with a k cat /K M > 10 4 M −1 s −1 [126,129].…”

New Mammalian Glycerol-3-Phosphate Phosphatase: Role in β-Cell, Liver and Adipocyte Metabolism

“…Toxic metabolic side products are generated in cells due to mutations in enzymes, changes in metabolic flux or due to the enzyme reaction with alternative substrates at low rates as the specificity of many enzymes is not absolute. Thus, it was shown that GAPDH can also catalyze the conversion of the pentose phosphate pathway metabolite erythrose-4-phosphate to 4phosphoerythronate ( 51), though at a much lower rate (32) (33,53), it was suggested that G3PP/PGP can act like a 'metabolic repair enzyme' and hydrolyze these two toxic metabolites. However, as the concentrations of these metabolites in wild type cells with normal expression of G3PP/PGP are much lower than their corresponding Km for purified mouse G3PP/ PGP, it is plausible that only under stress conditions when these metabolites accumulate significantly, G3PP/PGP may hydrolyze them and act as a detoxification enzyme of various phosphometabolites, besides its action on Gro3P.…”

“…4-Phosphoerythronate and 2-phospholactate were shown to inhibit 6-phosphogluconate dehydrogenase and phosphofructokinase-2, respectively ( 32 ). As 4-phosphoerythronate and 2-phospholactate accumulate only in PGP deleted HCT116 cells ( 32 ) and malarial parasite Plasmodium ( 33 , 53 ), it was suggested that G3PP/PGP can act like a ‘metabolic repair enzyme’ and hydrolyze these two toxic metabolites. However, as the concentrations of these metabolites in wild type cells with normal expression of G3PP/PGP are much lower than their corresponding Km for purified mouse G3PP/PGP, it is plausible that only under stress conditions when these metabolites accumulate significantly, G3PP/PGP may hydrolyze them and act as a detoxification enzyme of various phospho-metabolites, besides its action on Gro3P.…”