OK, I've read the manuscript now. Very interesting work. I didn't realize this initially, but they are also saying that the transient phosphorylation of PGAM1 i

OK, I've read the manuscript now. Very interesting work. I didn't realize this initially, but they are also saying that the transient phosphorylation of PGAM1 is a mechanism by which PEP is converted to pyruvate at a meaningful rate! Reason for the exclamation point: the conversion of PEP -> pyruvate is is considered the last of 3 rate-limiting steps in glycolysis. They propose an end-run around this rate-limiting step. In their model, PEP donates its phosphate to PGAM1. Thus, PEP becomes pyruvate. Normally I wouldn't expect this to be a meaningful way to produce pyruvate--but their data appear to support the notion that PGAM1 becomes dephosphorylated at a high enough rate that this process can repeat itself fast enough to sustain pyruvate production. Oh, and phosphorylated PGAM1 isn't just a temporary phosphate holder--they hypothesize (relying on other studies) that it helps shunt carbons into biosynthetic pathways (which you need if you are a proliferating cancer). It's not every day that someone figures out how living cells bypass a canonical rate-limiting step in the fundamental metabolic process shared by all living things.