Question

The synthesis of lipids in cancer cells is dependent upon mitochondrial citrate, which is derived from both glucose and glutamine.

A)  True    

B)  False

Answer 1

The cancer cells rapidly proliferate and so require a constant supply of building blocks to generate daughter cells. A boost in lipid synthesis is important  for supporting proliferation because, in addition to serving the signaling functions, lipids are the essential structural components of cellular membranes.

Glucose is metabolized via a series of reactions known as glycolysis to generate pyruvate (it involves various enymes). Pyruvate is then imported into mitochondria where it is converted to acetyl-coenzyme A (acetyl-CoA) by the pyruvate dehydrogenase (PDH) enzyme complex . Acetyl-CoA then condenses with oxaloacetate to enter the tricarboxylic acid cycle (TCA cycle, also known as the Krebs cycle or citric acid cycle), which provides energy in the form of ATP via the oxidative phosphorylation chain. Also, pyruvate is converted to lactate by cytoplasmic lactate dehydrogenase (LDH).

In cancer cells the relative amount of pyruvate oxidized to lactate as compared to that metabolized via the TCA cycle is higher compared to normal cells. However, in many cancer cells, a fraction of glucose-derived acetyl-CoA is also incorporated into lipids. This is because mitochondrial citrate exits into the cytoplasm, where the enzyme ATP citrate lyase (ACL) converts it to acetyl-CoA and oxaloacetate . The cytoplasmic acetyl-CoA can then be utilized for lipid synthesis.

In cancer cells glutamine catabolism involves its conversion to glutamate by glutaminase in mitochondria. Glutamate is, in turn, deaminated to generate α-ketoglutarate (α-KG). α-KG can then enter the TCA cycle and keep it going when glucose-derived citrate is re-routed to the cytoplasm. This function of glutamine is referred to as “anaplerosis”

Hence the given statement is TRUE