carnitine shuttle

Definition

Target type: biologicalprocess

The transfer of acyl groups to and from acyl-CoA molecules to form O-acylcarnitine, which can exchange across the mitochondrial inner membrane with unacylated carnitine. [ISBN:0198547684]

The carnitine shuttle is a critical process for transporting long-chain fatty acids (LCFAs) across the mitochondrial membrane, allowing them to be oxidized for energy production. This process occurs in three main steps:

1. **Activation of fatty acids:** LCFAs in the cytoplasm are first activated by attaching Coenzyme A (CoA) to form fatty acyl-CoA, using energy from ATP. This reaction is catalyzed by acyl-CoA synthetase.

2. **Translocation across the outer mitochondrial membrane:** Fatty acyl-CoA then diffuses across the outer mitochondrial membrane, which is permeable to most small molecules.

3. **Translocation across the inner mitochondrial membrane:** The inner mitochondrial membrane, however, is impermeable to fatty acyl-CoA. Here, the carnitine shuttle comes into play.

a. **Carnitine palmitoyltransferase I (CPT I):** Located on the outer surface of the inner mitochondrial membrane, CPT I catalyzes the transfer of the fatty acyl group from CoA to carnitine, forming fatty acyl-carnitine.

b. **Translocation through the inner membrane:** Fatty acyl-carnitine is then transported across the inner mitochondrial membrane by a specific transporter protein called carnitine acylcarnitine translocase (CACT).

c. **Carnitine palmitoyltransferase II (CPT II):** Once inside the mitochondrial matrix, CPT II, located on the inner surface of the inner mitochondrial membrane, catalyzes the transfer of the fatty acyl group back to CoA, regenerating fatty acyl-CoA and releasing carnitine.

4. **Beta-oxidation:** The fatty acyl-CoA within the mitochondria can now undergo beta-oxidation, a process that breaks down fatty acids into acetyl-CoA, which then enters the citric acid cycle for further energy production.

The carnitine shuttle plays a crucial role in energy metabolism, particularly during prolonged fasting or exercise, when the body relies heavily on fat oxidation for energy. It also regulates the levels of fatty acyl-CoA in different cellular compartments, ensuring efficient energy production and preventing accumulation of toxic fatty acids.

Defects in the carnitine shuttle, such as deficiencies in CPT I or CACT, can lead to various metabolic disorders affecting energy production and muscle function. These disorders are often characterized by hypoglycemia, muscle weakness, and accumulation of fatty acids in the blood and tissues.'
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Proteins (6)

Compounds (15)