Fig. 4

Peroxisomal and mitochondrial fatty acid oxidation. Short- and medium-chain fatty acyl-CoAs freely diffuse into the mitochondria and enter beta oxidation, whereas long-chain fatty acyl-CoAs are transported into the mitochondria via the CPT system. Saturated fatty acyl-CoAs directly enter the beta oxidation pathways, whereas unsaturated fatty acyl-CoAs switch between beta oxidation and the auxiliary pathways which process the double bonds. Beta oxidation shortens fatty acyl-CoAs by two carbons to produce acetyl-CoA which is a substrate for the TCA cycle and ATP generation. Very-long chain fatty acyl-CoAs are transported into peroxisomes via ABCD transporters and undergo oxidation to shorten the fatty acyls and produce acyl-carnitines by carnitine octanoyltransferase which are transported to the mitochondrial, where they are converted to fatty acyl-CoAs by the actions of CPT2. Peroxisomal oxidation also produces acetyl-CoA that can be converted to acetylcarnitine by carnitine acetyltransferase or to acetate by acyl-CoA thioesterases. Mitochondrial fatty acid oxidation is reduced by allosteric inhibition of CPT1 by malonyl-CoA which is produced via ACC2 from acetyl-CoA, which itself generated by acetate by ACSS. ABCD ATP-binding cassette transporters, ACAA2 3-ketoacyl-CoA thiolase, ACAD acyl-CoA dehydrogenase, ACC2 acetyl-CoA carboxylases, ACOT acyl-CoA thioesterases, ACSS2 cytoplasmic acetyl-CoA synthetase, CACT carnitine acylcarnitine translocase, CAT carnitine acetyltransferase, COT carnitine octanoyltransferase, CPT1 carnitine palmitoyltransferase 1, CPT2 carnitine palmitoyltransferase 2, ETC electron transport chain, ECH enoyl-CoA hydratase, ECI Δ3, Δ2-enoyl-CoA isomerase, DECR1 2,4-dienoyl CoA-reductase, HADH hydroxyacyl-CoA dehydrogenase, FA-CoA fatty acyl-CoA, S-FAs saturated fatty acids, Un-FAs unsaturated fatty acids including MUFAs and PUFAs, VLCFA-CoA very-long chain fatty acyl-CoA