Mitochondrial CPT System
Explore and order pathway-specific siRNAs, real-time PCR assays, and expression vectors. View pathway information and literature references for your pathway.
  • Click on your proteins of interest in the pathway image or review below
  • Select your genes of interest and click "add selection"
  • When you have finished your gene selection, click "Find Products" to find assays, arrays, or create custom products
Download Image Terms of Use Download PPT
Pathway Navigator
Mitochondrial CPT System

Carnitine (L-Carnitine or 3-hydroxy-4-(trimethylammonio) butanoate) and its Acyl-Esters (Acyl-Carnitines or ROC-Carnitine) are essential compounds for the metabolism of fatty acids (or RCOOH compounds). Carnitine is synthesized de novo in animal cells, but it is believed that most comes from the diet. Its main function is to assist the transport and metabolism of fatty acids into mitochondria, where they are oxidized for energy production. Carnitine maintains a balance between free and esterified CoA (Coenzyme A or CoASH), since an excess of Acyl-CoA (or ROC-CoA) intermediates are potentially toxic to cells. In addition, Carnitine is required to remove any surplus of Acyl groups from mitochondria. Fatty acids are first activated by CoA, i.e. to form highly polar Thiol esters, Acyl-CoA, on the outer mitochondrial membrane. As these cannot cross the inner mitochondrial membrane, the Acyl group is first transferred to Carnitine with formation of Acyl-Carnitines, which then enter the mitochondria with the assistance of specific translocases. The mitochondrial CPT (Carnitine Palmitoyl Transferase) system is composed of two proteins, CPTI (Outer Membrane Carnitine Palmitoyl Transferase) and CPTII (Carnitine Palmitoyl Transferase-II), which, together with the CACT (Carnitine-Acylcarnitine Translocase), are involved in the transport of fatty acids into the mitochondrial matrix for Beta-Oxidation. CPTI is present in the mitochondrial outer membrane, CACT is an integral inner membrane protein and CPTII is located on the matrix side of the inner membrane (Ref.1). Then, inside the mitochondria, Carnitine and Acyl-CoA are regenerated, and the latter is catabolized in two-carbon units by Beta-oxidation, with production of Acetyl-CoA in normal circumstances. The the Acetyl groups are transported out of mitochondria in the form of Acetyl-Carnitine. The Beta-Oxidation of fatty acids is an important source of energy for ATP (Adenosine Triphosphate) production in mitochondria through the entry of Acetyl-CoA into the Krebs cycle and Electron Transport System. NADH (Nicotinamide Adenine Dinucleotide, Reduced) and FADH2 (Flavin Adenine Dinucleotide, Reduced) further stimulate the production of ATP. Ketone bodies are produced by the process of Ketogenesis, which occurs when Acetyl-CoA accumulates beyond its capacity to be oxidized or used for fatty acid synthesis (Ref.2).

Activated MCFAs (Medium-Chain Fatty-Acids) (C8 and C10) freely diffuse into mitochondria to be oxidized but LCFAs (Long-Chain Fatty-Acids) do not diffuse into mitochondria so they must be transported in. The transport of LCFAs into mitochondria for oxidation is accomplished by ACS (Acetyl-CoA Synthetase or Acetate-CoA Ligase), CPTI and CPTII. CPTI exchanges Carnitine for the CoA attached to LCFAs to form a fatty acid-Carnitine conjugate or Acyl-Carnitine. The Acyl-Carnitine is transported into the matrix by a transporter protein in the inner mitochondrial membrane. Once the Acyl-Carnitine is inside the matrix,CPTII exchanges CoA for Carnitine to produce Acyl-CoA once again, ready to enter fatty acid oxidation in the matrix to produce energy (Ref.3). The free Carnitine is transported back out to renew the cytoplasmic pool of Carnitine and allow the transfer process to continue. A number of enzymes are involved in the Beta-Oxidation process. Deficiencies in any of these enzymes cause in accumulation of Acyl-CoA of specific chain-lengths and these have toxic effects if they are not removed by formation of Acyl-Carnitines. Several inherited metabolic diseases are identified from the presence of Acyl-Carnitines in the blood and urine of neonates and from their chain-length profile, the point of the breakdown in the Beta-Oxidation pathway and the disease involved is recognized (Ref.4).