Question

Following a severe cold which caused a loss of appetite, a 1 -year-old boy was hospitalized with hypoglycemia, hyperammonemia, muscle weakness, and cardiac irregularities. These symptoms were consistent with a defect in the carnitine transport system. Dietary carnitine therapy was tried unsuccessfully, but a diet low in long-chain fatty acids and supplemented with medium-chain triacylglycerols was beneficial. Carnitine transport of fatty acids from the cytosol to the mitochondria involves all of the following except A. hydrolysis of ATP. B. the exchange of acylcarnitine and free carnitine across the inner mitochondrial membrane. C. two carnitine palmitoyl transferases (CPT I and CPT II) located on different mitochondrial membranes. D. release of CoASH from fatty acyl CoA in the cytosol. E. consumption of mitochondrial CoASH.

Short answer

A. Hydrolysis of ATP B. Exchange of acylcarnitine and free carnitine across the inner mitochondrial membrane C. The involvement of two carnitine palmitoyl transferases (CPT I and CPT II) D. Release of CoASH from fatty acyl CoA in the cytosol E. Consumption of mitochondrial CoASH Answer: A. Hydrolysis of ATP

Step-by-step solution

Formation of fatty acyl CoA in the cytosol

Fatty acids are first activated by conjugation with coenzyme A (CoASH) in the cytosol, forming fatty acyl CoA.

Carnitine Palmitoyl Transferase I (CPT I)

The fatty acyl CoA encounters the enzyme Carnitine Palmitoyl Transferase I (CPT I), located on the outer mitochondrial membrane. CPT I catalyzes the transfer of the acyl group from the fatty acyl CoA molecule to carnitine, forming acylcarnitine and releasing free CoASH.

Acylcarnitine transport across the inner mitochondrial membrane

Acylcarnitine is then transported across the inner mitochondrial membrane in exchange for free carnitine via a specific carnitine-acylcarnitine translocase.

Carnitine Palmitoyl Transferase II (CPT II)

Once inside the mitochondria, the enzyme Carnitine Palmitoyl Transferase II (CPT II), located on the inner mitochondrial membrane, transfers the acyl group back from the acylcarnitine to a coenzyme A molecule, forming fatty acyl CoA and releasing free carnitine.

Beta-oxidation of fatty acyl CoA

The fatty acyl CoA inside the mitochondria then undergoes beta-oxidation for energy production. Now, let's go through the options and find out which one is not involved in the carnitine transport system: A. Hydrolysis of ATP is not required in the carnitine transport system. B. Exchange of acylcarnitine and free carnitine across the inner mitochondrial membrane is part of the process (Step 3). C. The involvement of two carnitine palmitoyl transferases (CPT I and CPT II) is also part of the process (Steps 2 and 4). D. Release of CoASH from fatty acyl CoA in the cytosol occurs during the action of CPT I (Step 2). E. Consumption of mitochondrial CoASH takes place when the acyl group is transferred back to coenzyme A by CPT II (Step 4). Answer: The correct option is A. Hydrolysis of ATP is not involved in the carnitine transport system.