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A 20 year-old- male presents with intermittent ataxia (abnormal gait), paralysis of eye muscles, and confusion. After an extensive work up, he is diagnosed with Carnitine acyl transferase I(CAT-I) deficiency. The reaction catalyzed by CAT-I forms-

A) Fatty acyl co A

B) Fatty acyl Carnitine

C) Malonyl co A

D) Palmitoyl co A

E) Carnitine


Answer- The right option is B- Fatty acyl carnitine.

Fatty acids are activated on the outer mitochondrial membrane, whereas they are oxidized in the mitochondrial matrix. A special transport mechanism is needed to carry long-chain acyl CoA molecules across the inner mitochondrial membrane. Activated long-chain fatty acids are transported across the membrane by conjugating them to carnitine, a zwitterionic alcohol.

Carnitine (ß-hydroxy-Υ-trimethyl ammonium butyrate), (CH3)3N+—CH2—CH(OH)—CH2—COO, is widely distributed and is particularly abundant in muscle. Carnitine is obtained from foods, particularly animal-based foods, and via endogenous synthesis.

The transportation across the inner mitochondrial membrane through carnitine shuttle involves three steps-

1) The acyl group is transferred from the sulfur atom of CoA to the hydroxyl group of carnitine to form acyl carnitine. This reaction is catalyzed by carnitine acyl transferase I (also called carnitine palmitoyl transferaseI), which is bound to the outer mitochondrial membrane.

2) Acyl carnitine is then shuttled across the inner mitochondrial membrane by a translocase.

3) The acyl group is transferred back to CoA on the matrix side of the membrane. This reaction, which is catalyzed by carnitine acyl transferase II (carnitine palmitoyl transferase II), is simply the reverse of the reaction that takes place in the cytosol.

Finally, the translocase returns carnitine to the cytosolic side in exchange for an incoming acyl carnitine (Figure)

Figure- showing the transportation of acyl co A in to to the mitochondrial matrix through carnitine shuttle

This counter-transport system provides regulation of the uptake of fatty acids into the mitochondrion for oxidation. As long as there is free CoA available in the mitochondrial matrix, fatty acids can be taken up and the carnitine returned to the outer membrane for uptake of more fatty acids. However, if most of the CoA in the mitochondrion is acylated, then the fatty acid uptake is inhibited.

This carnitine shuttle also serves to prevent uptake into the mitochondrion (and hence oxidation) of fatty acids synthesized in the cytosol in the fed state; malonyl CoA (the precursor for fatty acid synthesis) is a potent inhibitor of carnitine palmitoyl transferase I in the outer mitochondrial membrane.

Short and medium chain fatty acids do not require carnitine for their transportation across the inner mitochondrial membrane.

Inherited CAT-I deficiency affects only the liver, resulting in reduced fatty acid oxidation and ketogenesis, with hypoglycemia. CAT-II deficiency affects primarily skeletal muscle and, when severe, the liver.

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