Figure 1.

Acetyl-CoA production from fatty acid and glucose metabolism in muscle mitochondria. Fatty acids enter the cells by fatty acid transporters. Once in the cell they are activated to fatty acyl-CoA by acyl-CoA synthetase (ACS) before entering the mitochondria. At the level of the outer part of the outer mitochondrial membrane (OMM), fatty acyl-CoAs are bind to carnitine, by carnitine palmitoyltransferase-1 (CPT-1) activity, to form fatty acylcarnitine derivatives which diffuse through the outer mitochondrial membrane. Thus, the formed fatty acylcarnitines are transported across the inner mitochondrial membrane (IMM) via carnitine-acylcarnitine translocase (CACT). In the mitochondrial matrix, CPT-2 converts fatty acylcarnitines back to fatty acyl-CoAs, which enters the β-oxidation pathway, and to free carnitine which can exit from the mitochondria in exchange with other acylcarnitines through CACT. Mitochondrial acetyl-CoA is generated from both β-oxidation of fatty acids and from pyruvate. Pyruvate is formed in the glycolytic pathway form glucose which enters the muscle cell via the glucose transporter type 4 (GLUT4). Pyruvate is transported in the mitochondrial matrix by the pyruvate carrier (MPC) of the inner mitochondrial membrane. Once in the mitochondria, pyruvate is converted into acetyl-CoA throughout the complex of the pyruvate dehydrogenase (PDH). This acetyl-CoA, together with that formed in the β-oxidation pathway can enter the tricarboxylic acid cycle (TCA cycle) to produce equivalent donors in the form of NADH (H⁺) and FADH₂ which are oxidized in the mitochondrial electron transport chain to produce ATP.