Figure 3.

Glutamine metabolism in the mitochondrion and malonate metabolism in the cytosol. The Figure shows glutamine metabolism, which eventually leads to the formation of lactate in the cytosol. This process is dependent on two groups of enzymes: mitochondrial and cytosolic. Inside the mitochondrion, glutamine is deaminated by GLS1 or GLS1 to glutamate and a waste product (ammonia). Then, glutamate is dehydrogenated by GLDH to α-ketoglutarate, which could be directly incorporated into the TCA cycle or indirectly incorporated after carboxylation to isocitrate. Some α-ketoglutarate in mitochondrion is converted to malonate. This molecule crosses the mitochondrial membrane and reaches the cytosolic space. Here, the last pathway step occurs: malate dehydrogenation by LDHA, leading to the formation of lactate. GLS1, GLS2—glutaminase 1, glutaminase 2; GLDH —glutamate dehydrogenase; LDHA—lactate dehydrogenase A; TCA—tricarboxylic acid.