General Information:

Id: 6,362 (click here to show other Interactions for entry)
Diseases: Cancer
Diabetes mellitus, type II - [OMIM]
Insulin resistance
Mammalia
review
Reference: Anastasiou D and Cantley LC(2012) Breathless cancer cells get fat on glutamine Cell Res. 3: 443-446 [PMID: 22212478]

Interaction Information:

Comment Rather than generating citrate going through the forward, oxidative, direction of the TCA cycle, glutamine utilizes another route that involves the reductive carboxylation of glutamine-derived alpha-ketoglutarate (alpha-KG). As much as 25% of acetyl-CoA utilized for lipid synthesis was generated by this route of glutamine catabolism in various cell lines under normoxic conditions, the rest of the carbons being contributed by glucose. When the source of lipogenic acetyl-CoA was probed under hypoxia, less glucose is used for lipid synthesis, consistent with the notion that hypoxia limits pyruvate entry into mitochondria. Under these conditions, however, glutamine took over the role of the major carbon source for lipogenesis via the reductive carboxylation route. Treatment of cells with dichloroacetate (DCA), which inhibits PDK1 and therefore alleviates inhibition of PDH, partly restored glucose-dependent lipogenesis and diminished reductive glutamine metabolism under hypoxia.
Formal Description
Interaction-ID: 59792

increases_activity of

process

reductive glutamine metabolism