Fatty acyl–carnitine can diffuse from the cytosol across the porous outer mitochondrial membrane to the intermembrane space, but must utilize CACT to cross the nonporous inner mitochondrial membrane and reach the mitochondrial matrix.[5] CACT is a cotransporter, returning one molecule of carnitine from the matrix to the intermembrane space as one molecule of fatty acyl–carnitine moves into the matrix.[6]
Clinical significance
A disorder is associated with carnitine-acylcarnitine translocase deficiency. This disorder disrupts the carnitine shuttle system from moving fatty acids across the mitochondrial membrane, leading to a decrease in fatty acid catabolism. The result is an accumulation of fatty acid within muscles and liver, decreased tolerance to long term exercise, inability to fast for more than a few hours, muscle weakness and wasting, and a strong acidic smell on the breath (due to protein catabolism).[7]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Ramsay RR, Gandour RD, van der Leij FR (March 2001). "Molecular enzymology of carnitine transfer and transport". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1546 (1): 21–43. doi:10.1016/s0167-4838(01)00147-9. PMID11257506.
^Lehninger A, Nelson D, Cox M, eds. (1992). Principles of biochemistry (2nd ed.). New York: Worth Publishers, Inc. p. 1012.
