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PHAR 332
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Quick review of fatty acid breakdown Clinical cases involving carnitine deficiency Back to Clinical Cases main page
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Long chain fatty acids are the major source of metabolic energy in humans, in particular for the heart and skeletal muscles. Persons with carnitine or carnitine palmitoyltransferase (CPT) deficiency are unable to metabolize long-chain fatty acids. In adults with this defect, the most common results are muscle weakness and hypoketosis, while in neonates this disease often leads to arrhythmias resulting in death. Carnitine is an amino acid that is required for the transport of long-chain fatty acids into the mitochondria, the site of beta-oxidation of fatty acids. About 25 percent of the carnitine required by the body is produced by the liver and kidneys, while the rest is derived from dietary intake, primarily from red meat, poultry, fish, and dairy products. Most of the carnitine in the body is located in the voluntary and cardiac muscles. There are two types of carnitine deficiency, primary and secondary. A person with primary carnitine deficiency has very low levels of carnitine in the blood due to a faulty carnitine transporter which prevents carnitine from getting into the cells where it is needed.The primary form of the disorder can be classified as either "systemic carnitine decificiency", which affects many organ systems including the heart and the brain, or "muscle carnitine deficiency", which is restricted to vouluntary muscles. The secondary form of carntine deficiency can arise secondary to metalobic disorders in the mitochondria. Blockage of metabolic pathways in the mitochondria leads to a build-up of acyl compounds. These compounds then bind to carnitine and the bound complex is then excreted by the kidney, causing carnitine levels to drop. Some of these mitochondrial disorders include cytochrome c oxidase deficiency, mitochondrial ATPase deficiency, and fatty acyl-CoA dehydrogenase deficiencies. In both primary and secondary carnintine deficiencies, increased dietary intake and supplements of carnitine can be beneficial. Although the exact mechanism is unknown, it is thought that flooding the body with high concentrations of carnitine assures that some carnitine are able to get into the cells.
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