Carnitine is a quaternary ammonium compounds synthesized from the amino acids lysine and methionine. In eukaryotes, carnitine is required for the transport of fatty acids from the intermembraneous space of the mitochondria into the mitochondrial matrix during the breakdown of lipids for the generation of metabolic energy. In animals, biosynthesis of carnitine primarily occurs in the liver and kidneys. However, carnitine may also be absorbed in the diet, primarily from red meats, but also in significantly lower levels in many other foods, such as, nuts and seed, legumes, vegetables, fruits, and cereals. Although carnitine naturally occurs in two stereoisomers, only the L-enantiomer is biologically active. The efficacy of L-carnitine has been reported for numerous applications. It is an important dietary/nutritional supplement. L-carnitine has been widely used in the food industry and may also be therapeutically effective.
Acetyl-L-carnitine and propionyl-L-carnitine are derivatives of L-carnitine that are naturally produced in the body. For example, during strenuous exercise, L-carnitine and used acetyl-CoA are converted into acetyl-L-carnitine and CoA by carnitine acetyltransferase inside the mitochondria. Acetyl-L-carnitine is then transported outside of mitochondria and converted back to L-carnitine, for example, by plasma esterases in the blood, before it is cycled back into the mitochondria for transporting of fatty acid. The mechanism of propionyl-L-carnitine biosynthesis is similar to that of acetyl-L-carnitine. Instead of converting L-carnitine and acetyl-CoA, carnitine acetyltransferase converts L-carnitine and propionyl-CoA in the mitochondria into propionyl-L-carnitine and CoA.
Both acetyl-L-carnitine and propionyl-L-carnitine are believed to have many advantageous properties over L-carnitine, such as increased bioavailability. For example, researchers prefer to use acetyl-L-carnitine to study the effects of carnitine in the body, because it has better absorption than L-carnitine in the small intestine and is more able to cross the blood/brain barrier.
Notwithstanding, the typical method of production for propionyl-1-carnitine and acetyl-1-carnitine involves the reaction of propionyl chloride and acetyl chloride respectively. During the reaction the end product would be propionyl-1-carnitine/acetyl-1-carnitine which would readily react with the hydrochloric acid formed by the reaction to wield the respective hydrochloride salts (acetyl-1-carnitine hydrochloride and propionyl-1-carnitine hydrochloride). Being a strong inorganic acid, HCl is practically impossible to replace with nitric acid and other acids to achieve nitrate and other salts of acetyl and propionyl 1-carnitine. Thus, to this day, acetyl and propionyl carnitine are offered only as hydrochloride salts for sale and use in the supplement industry.
USPTO Backgrounds
USPTO Backgrounds