Figure 1. Schematic presentation of the uptake and utilization of long-chain (LC) fatty acids (FA) by parenchymal cells, with emphasis on the assumed or proposed role of various lipid-binding proteins in this process. See comments in text. Abbreviations: Chylo, chylomicrons; VLDL, very low-density lipoproteins; Alb. BP, albumin-binding protein; FABPpm, plasmalemmal fatty acid-binding protein; FAT, fatty acid translocase (CD36); FATP, fatty acid transport protein; FABPc, cytoplasmic fatty acid-binding protein; ACS, acyl-CoA synthetase; ACBP, acyl-CoA-binding protein. Reproduced from Luiken JJ et al. (1999) Lipids 34 (supplement): S169–S175, by permission of AOCS Press.

Figure 2. Complex formed by carnitine palmitoyltransferases (CPT-I and CPT-II) at contact sites in the mitochondrial membranes for the transport of long-chain fatty acids to the mitochondrial matrix. 1, Traditional representation of the association between CPT-I, CPT-II and carnitine acylcarnitine translocase (CACT). This theory suggests that the CPT-I active site is located within the outer membrane (for more details see Park and Cook, 1998). 2, Recent evidence suggests that the CPT-I active site faces the cytosol and that CACT is less expressed at contact sites and more uniformly distributed in the mitochondrial inner membrane, and therefore does not necessitate direct contact with CPT-I and II (for more details see Zammit, 1999). Abbreviations: LCFA, long-chain fatty acids; FABPc, cytoplasmic fatty acid-binding protein; ACS, acyl-CoA synthetase; LC acyl-CoA, long-chain acyl-CoA; ACBP, acyl-CoA-binding protein.

Figure 3. Location of various carnitine acyltransferases and proposed regulation of fatty acid channelling in the subcellular organelles of hepatocytes. (a) Fed state: glucose metabolism causes citrate to increase in the mitochondria, which ultimately causes malonyl-CoA to increase, thereby inhibiting the activity of malonyl-CoA-sensitive carnitine palmitoyltransferases (CPT-I, CPTo). Fatty acids cannot enter the subcellular organelles and are likely to be esterified into triacylglycerol (TAG) in the cytosol. Peroxisomal -oxidation is increased and/or more complete, probably owing to an inhibition of carnitine octanoyltransferase (COT) or through a still unknown process, which may involve the accumulation of long-chain acyl-CoA and dicarboxylic acids. (b) Fasted state: very long-chain and long-chain acyl-CoA are transported into the subcellular organelles via the malonyl-CoA-sensitive carnitine palmitoyltransferases (CPT-I, CPTo) for subsequent metabolism: -oxidation and ketogenesis in the mitochondria, -oxidation in the peroxisomes, TAG esterification in the endoplasmic reticulum. Abbreviations: VLC and LC-acyl-CoA, very long-chain and long-chain acyl-CoA; ACBP, acyl-CoA-binding protein; CPT-I and CPT-II, carnitine palmitoyltransferases I and II; p-CPTo, peroxisomal CPTo; m-CPTo, microsomal CPTo; COT, carnitine octanoyltransferase; CPTm, microsomal CPT; CAT, carnitine acetyltransferase; TAG, triacylglycerol; TCA cycle, tricarboxylic acid cycle; ACC, acetyl-CoA carboxylase; MCD, malonyl-CoA decarboxylase.

Figure 4. The -oxidation pathway of saturated acyl-CoA in the mitochondria.

Figure 5. The -oxidation pathway of unsaturated acyl-CoA in the mitochondria. Linoleic acid is used as an example.

Figure 6. The -oxidation pathway of saturated acyl-CoA in the peroxisomes.

Figure 7. The -oxidation pathway of phytanic acid (for more details see Wanders RJ (2000) Cell Biochemistry and Biophysics 32: 89–106).