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Carnitine Transport System

The carnitine transport system (also the carnitine-acyltransferase system , carnitine shuttle ) is one of several mitochondrial transport systems that transfer acyl-CoA via acylation of carnitine in the cytoplasm, through mitochondrial membranes into the matrix (transmembrane transfer). The system includes several enzymes: carnitine acyltransferase (also carnitine palmitoyl transferase , abbr. CPT) and a carrier protein - carnitine acyl carnitine translocase (abbreviation CACT). These enzymes are membrane proteins .

Content

  • 1 Structure and transport mechanism
  • 2 Pathology
  • 3 Notes
  • 4 See also

Transfer structure and mechanism

 
Carnitine transport system. The diagram shows the structure and mechanism of transfer of fatty acids in the form of acyl-CoA. Free fatty acids (FFAs) with short and medium chain lengths in the form of esters - acyl-CoA easily diffuse through mitochondrial membranes, however, most of these fatty acids have a long hydrocarbon chain, which does not allow them to pass freely. This requires a carrier, which serves as carnitine - 1 . On the surface of the outer mitochondrial membrane there is an enzyme acylating free carnitine to acylcarnitine (carnitine-COR) 2 - carnitine-palmitoyl transferase I (CPT1), which diffuses through the outer membrane and penetrates into the intermembrane space. The inner mitochondrial membrane is impervious to acylcarnitine, in order to pass through it there is carnitine-acylcarnitine translocase (CACT), which allows its transport to the matrix . Further, acylcarnitine undergoes the reverse process - cleavage by the enzyme carnitine-palmitoyltransferase II (CPT2) and calculus A into free carnitine and acyl-CoA, which enters into β-oxidation . Free carnitine 1 is transported by the same translocase through the inner membrane into the intermembrane space of the mitochondria and then diffuses into the cytoplasm .

Activated short and medium hydrocarbon chain fatty acids can easily penetrate the mitochondrial double membrane, but most fatty acids have a long chain that interferes with the penetration of these acids into the inside. For this transfer, mitochondria have a system that allows such fatty acids to be transported through membranes via a carnitine shuttle. Fatty acids in the form of acyl-CoA become transportable in the cytoplasm of cells only after interaction with carnitine . The reaction mechanism is the transfer of an acyl group (COR) from an acyl-CoA molecule to a substrate - carnitine. The reaction is catalyzed by the enzyme carnitine-palmitoyltransferase I (CPT1). The resulting acylcarnitine diffuses through the outer membrane into the intermembrane space of the mitochondria to the inner membrane. The inner membrane is not permeable to acylcarnitine and, therefore, it is transported by a carrier protein - carnitine-acylcarnitine translocase (CACT), which penetrates through the inner membrane of mitochondria (it is a transmembrane protein ). This enzyme carries out the transfer of acylcarnitine by facilitating diffusion into the matrix . Further, acylcarnitine, under the action of coenzyme A (CoA-SH) and the carnitine-palmitoyltransferase II (CPT2) enzyme (located on the inner side of the inner membrane), is split into carnitine and acyl-CoA, which undergo further β-oxidation . Using the same translocase, carnitine is transferred into the intermembrane space and freely diffuses into the cytoplasm, where it is again acylated. The equations for the reactions of transfer of acyl-CoA to the matrix via the carnitine shuttle are as follows:

R-CO ~ SCoA + carnitine ↔ carnitine-COR + CoA-SH

and

CoA-SH + Carnitine-COR ↔ R-CO ~ SCoA + Carnitine

The first equation characterizes the acylation of carnitine, the second - the inverse process with the formation of acyl-CoA.

Pathology

Pathologies of the carnitine transport system are associated with genetic defects of the components that make up its composition. The most common is a deficiency of carnitine-palmitoyltransferase I.

Notes

See also

  • Beta oxidation
  • Carnitine O-Palmitoyltransferase
Source - https://ru.wikipedia.org/w/index.php?title=Carnitine_transport_system&oldid=83982937


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Clever Geek | 2019