Carnitine Palmitoyltransferase (CPT) 

Carnitine palmitoyltransferase (CPT) is the central rate-limiting enzyme system for mitochondrial fatty acid β-oxidation, capable of converting palmitoyl-CoA into palmitoylcarnitine^[1][2]. CPT transports long-chain acyl-CoA into the mitochondrial matrix, where it undergoes a transesterification reaction with free carnitine to generate acylcarnitine—the sole form in which long-chain fatty acids can traverse the mitochondrial inner membrane. The complete carnitine cycle is cooperatively executed by CPT1 on the mitochondrial outer membrane, CPT2 on the inner face of the inner membrane, and carnitine-acylcarnitine translocase (CACT), which mediates the exchange of acylcarnitine and free carnitine across the inner membrane. The activity of CPT directly determines the efficiency of cellular fatty acid oxidation^[3][4]. The CPT1 enzyme system comprises three major isoforms: CPT1A (liver isoform), CPT1B (muscle isoform), and CPT1C (brain isoform). These isoforms exhibit significant differences in tissue distribution, functional regulation, and physiological and pathological roles, collectively constituting a complex metabolic regulatory network. In metabolic diseases (such as non-alcoholic steatohepatitis and obesity), the downregulation of CPT1A expression impairs fatty acid oxidation, thereby triggering lipid accumulation; conversely, in various malignancies, CPT1A is frequently overexpressed, providing energy for tumor cell proliferation and mediating drug resistance, thus serving as a critical node in metabolic reprogramming^[3][4]. CPT1A activity is primarily subject to physiological inhibition by malonyl-CoA; however, under pathological conditions, it is subject to transcriptional regulation by various signaling pathways, including JAK2/STAT3 and AMPK. Furthermore, recent studies have revealed that CPT1A possesses non-metabolic functions, such as the regulation of histone acetylation. Intervention strategies targeting CPT vary markedly depending on the specific disease context: in metabolic disorders, activating CPT1A is required to enhance fatty acid oxidation—a process that can be upregulated, for instance, by the traditional Chinese medicine compound *Qushi Huayu* formula; conversely, in anti-tumor research, inhibiting CPT1A may be necessary to disrupt the energy supply, with inhibitors such as DHP-B having already demonstrated promising anti-tumor efficacy^[1][2]. The CPT system has emerged as a pivotal molecular link connecting lipid metabolism with cell fate, positioning itself at the nexus—and as a major research hotspot—across diverse fields including metabolism, signal transduction, epigenetics, immunology, tumor biology, and precision medicine^[1][2][3][4].

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