Modeling Krebs cycle from liver, heart and hepatoma mitochondria, supported Complex I as target for specific inhibition of cancer cell proliferation.

ABSTRACT:

Introduction

The Krebs cycle (KC) is an important pathway for cancer cells because it produces reduced coenzymes for ATP synthesis and precursors for cellular proliferation. Described changes in cancer KC enzyme activities suggested modifications in the reactions that control the KC flux compared to normal cells.

Methods

In this work, kinetic metabolic models of KC of mitochondria from cancer (HepM), liver (RLM) and heart (RHM) to identify targets to decrease the KC flux were constructed from kinetic parameters (Vmax and Km) of enzymes here determined.

Results

The enzymes Vmax values were higher in the following order: RHM > HepM > RLM; meanwhile, Km values were similar. Kinetic modeling indicated that the NADH consumption reaction (complex I) exerted higher control o

SUBMITTER: Hernandez-Esquivel L 

PROVIDER: S-EPMC11979947 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature