Lipids and amino acids can also be used as energy sources, but they enter the main pathways at different points. C. elegans has a functional methylmalonyl-CoA epimerase (racemase) that is involved in propionyl-CoA metabolism for the degradation of branched amino acids and odd-chain fatty acids ( Kühnl et al., 2005 ). Fatty acid moieties of lipids are broken down by β -oxidation into acetyl-CoA (which in turn can enter the TCA cycle). β -oxidation occurs in the mitochondrial matrix and also yields reduced electron carriers. Peroxisomal β -oxidation of long-chain fatty acids is not linked directly to energy metabolism because the reduced electron carrier is directly oxidized by molecular oxygen (yielding hydrogen peroxide). Amino acids can be broken down via distinct pathways and their carbon skeletons can be metabolized in the TCA cycle.
If OAA is converted to PEP by mitochondrial PEPCK, it is transported to the cytosol where it is a direct substrate for gluconeogenesis and nothing further is required. Transamination of OAA to aspartate allows the aspartate to be transported to the cytosol where the reverse transamination occurs yielding cytosolic OAA. This transamination reaction requires continuous transport of glutamate into, and 2-oxoglutatrate (α-ketoglutarate) out of, the mitochondrion. Therefore, this process is limited by the availability of these other substrates. Either of these latter two reactions will predominate when the substrate for gluconeogenesis is lactate. Whether mitochondrial decarboxylation or transamination occurs is a function of the availability of PEPCK or transamination intermediates.