FIGURE 10.

Proposed metabolic pathways causing SFA-induced apoptosis and loci of amino acid control. SFAs inhibit glycolysis flux and promote the decoupling of glycolysis and CAC (TCA cycle) fluxes associated with decreased cytosolic NAD⁺/NADH. NEAAs, such as glutamate, strongly enhance this process, probably through CAC activation. High cytosolic NAD⁺/NADH prevents lactate and glycerol 3-phosphate formation from pyruvate and DHAP, respectively. The decreased glycerol pool might also reduce triglyceride synthesis and increase FFA accumulation and ceramide synthesis. Ceramide synthesis is dependent upon non-essential amino acid availability but is not involved in apoptotic pathways. The MUFA oleate can prevent SFA-induced decoupling of glycolysis and CAC fluxes and normalize cytosolic redox possibly by reversing glycolysis inhibition.