Logical modelling reveals the PDC-PDK interaction as the regulatory switch driving metabolic flexibility at the cellular level.

ABSTRACT:

Background

Metabolic flexibility is the ability of an organism to switch between substrates for energy metabolism, in response to the changing nutritional state and needs of the organism. On the cellular level, metabolic flexibility revolves around the tricarboxylic acid cycle by switching acetyl coenzyme A production from glucose to fatty acids and vice versa. In this study, we modelled cellular metabolic flexibility by constructing a logical model connecting glycolysis, fatty acid oxidation, fatty acid synthesis and the tricarboxylic acid cycle, and then using network analysis to study the behaviours of the model.

Results

We observed that the substrate switching usually occurs through the inhibition of pyruvate dehydrogenase complex (PDC) by pyruvate dehydrogenase kinases

SUBMITTER: Tareen SH 

PROVIDER: S-EPMC6734263 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature