CPT2

CPT2 Full Name

carnitine palmitoyltransferase 2

CPT2 Introduction

CPT2 encodes carnitine palmitoyltransferase 2, a nuclear gene whose protein product resides on the inner mitochondrial membrane and catalyzes the conversion of long-chain acylcarnitines back to acyl-CoA esters, thereby completing the carnitine shuttle that transports long-chain fatty acids into the mitochondrial matrix for β-oxidation. This enzymatic reaction is thermodynamically and metabolically essential: once fatty acids traverse the intermembrane space as acylcarnitine conjugates, CPT2 removes the carnitine moiety and regenerates acyl-CoA, which then enters the β-oxidation spiral to produce acetyl-CoA for the tricarboxylic acid cycle and ATP synthesis. The enzyme functions as a monomer within the inner membrane and is ubiquitously expressed, with particularly high activity in tissues that depend heavily on fatty acid oxidation for energy — skeletal muscle, liver, and cardiac muscle. CPT2 activity is tightly regulated by the intramitochondrial malonyl-CoA to CoA ratio, which integrates nutrient-sensing signals with fatty acid oxidation flux.

Figure 1. Role of the CPT system in the long-chain FA oxidation. (Source: Wang M, et al. 2021)

Mutations in CPT2 cause CPT2 deficiency, an autosomal recessive disorder of long-chain fatty acid oxidation that represents the most common inherited disorder of lipid metabolism affecting skeletal muscle. Three clinical subtypes are recognized: a lethal neonatal form with multiorgan failure, brain malformations, and death within days; a severe infantile hepatocardiomuscular form presenting with hypoketotic hypoglycemia, cardiomyopathy, and hepatic failure; and a myopathic form — by far the most common — in which affected individuals experience recurrent episodes of muscle pain, weakness, and rhabdomyolysis with myoglobinuria, typically triggered by prolonged exercise, fasting, cold exposure, or intercurrent infections. The Ser113Leu missense mutation accounts for over 50% of alleles in the myopathic phenotype and is associated with residual enzyme activity of approximately 20-30%, consistent with the milder clinical course. Between attacks, patients are typically asymptomatic with normal serum creatine kinase, which often delays diagnosis. Acute episodes may progress to acute kidney injury secondary to myoglobinuria, requiring hemodialysis. Management centers on avoidance of precipitating factors, a carbohydrate-rich low-fat diet, and prompt intravenous dextrose during metabolic crises.

Alternate Names for CPT2

CPT2; carnitine palmitoyltransferase 2; carnitine palmitoyltransferase II , CPT1; carnitine O-palmitoyltransferase 2, mitochondrial; CPTASE; CPT II; carnitine palmitoyltransferase II; CPT1; IIAE4;

• 1. Wang M, et al. Carnitine Palmitoyltransferase System: A New Target for Anti-Inflammatory and Anticancer Therapy? Front Pharmacol. 2021 Oct 26;12:760581.
  2. Seferi S, et al. Carnitine Palmitoyltransferase II (CPT2) Deficiency: An Overlooked and Elusive Cause of Acute Kidney Injury. Cureus. 2024 Sep 29;16(9):e70442.