title: The Carnitine Palmitoyl Transferase (CPT) System and Possible Relevance for Neuropsychiatric and Neurological Conditions.
abstract: The carnitine palmitoyl transferase (CPT) system is a multiprotein complex with catalytic activity localized within a core represented by CPT1 and CPT2 in the outer and inner membrane of the mitochondria, respectively. Two proteins, the acyl-CoA synthase and a translocase also form part of this system. This system is crucial for the mitochondrial beta-oxidation of long-chain fatty acids. CPT1 has two well-known isoforms, CPT1a and CPT1b. CPT1a is the hepatic isoform and CPT1b is typically muscular; both are normally utilized by the organism for metabolic processes throughout the body. There is a strong evidence for their involvement in various disease states, e.g., metabolic syndrome, cardiovascular diseases, and in diabetes mellitus type 2. Recently, a new, third isoform of CPT was described, CPT1c. This is a neuronal isoform and is prevalently localized in brain regions such as hypothalamus, amygdala, and hippocampus. These brain regions play an important role in control of food intake and neuropsychiatric and neurological diseases. CPT activity has been implicated in several neurological and social diseases mainly related to the alteration of insulin equilibrium in the brain. These pathologies include Parkinson's disease, Alzheimer's disease, and schizophrenia. Evolution of both Parkinson's disease and Alzheimer's disease is in some way linked to brain insulin and related metabolic dysfunctions with putative links also with the diabetes type 2. Studies show that in the CNS, CPT1c affects ceramide levels, endocannabionoids, and oxidative processes and may play an important role in various brain functions such as learning.
authors.affiliation: Research, Innovation and Development, Sigma-tau Health Science International BV, Utrecht, Netherlands, ashraf.virmani@sigma-tau.it.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Virmani
authors.forename: Luigi
authors.initials: L
authors.lastname: Pinto
authors.forename: Otto
authors.initials: O
authors.lastname: Bauermann
authors.forename: Saf
authors.initials: S
authors.lastname: Zerelli
authors.forename: Andreas
authors.initials: A
authors.lastname: Diedenhofen
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Binienda
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
authors.forename: Feike R
authors.initials: FR
authors.lastname: van der Leij
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D002318:Cardiovascular Diseases / Q000201:enzymology; D002331:Carnitine / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002518:Ceramides / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology; D018450:Disease Progression; D004435:Eating / Q000502:physiology; D063388:Endocannabinoids / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia; D007328:Insulin / Q000378:metabolism; D007858:Learning / Q000502:physiology; D008052:Lipid Metabolism, Inborn Errors; D008316:Malonyl Coenzyme A / Q000378:metabolism; D024821:Metabolic Syndrome / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology; D008931:Mitochondria, Muscle / Q000201:enzymology; D009097:Multienzyme Complexes / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000201:enzymology*; D010084:Oxidation-Reduction; D020033:Protein Isoforms
chemical_list: D002518:Ceramides; D063388:Endocannabinoids; D005227:Fatty Acids; D007328:Insulin; D009097:Multienzyme Complexes; D020033:Protein Isoforms; D008316:Malonyl Coenzyme A; C577474:CPT1A protein, human; C542591:CPT1B protein, human; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine