Evidence for a direct cross-talk between malic enzyme and the pentose phosphate pathway via structural interactions.

ABSTRACT: Recent studies have revealed that the oxidative pentose phosphate pathway (PPP), malic enzyme (ME), and folate metabolism are the three major routes for generating cellular NADPH, a key cofactor involved in redox control and reductive biosynthesis. Many tumor cells exhibit altered NADPH metabolism to fuel their rapid proliferation. However, little is known about how NADPH metabolism is coordinated in tumor cells. Here we report that ME1 increases the PPP flux by forming physiological complexes with 6-phosphogluconate dehydrogenase (6PGD). We found that ME1 and 6PGD form a hetero-oligomer that increases the capability of 6PGD to bind its substrate 6-phosphogluconate. Through activating 6PGD, ME1 enhances NADPH generation, PPP flux, and tumor cell growth. Interestingly,

SUBMITTER: Yao P 

PROVIDER: S-EPMC5641861 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature