Metabolic Actions of Carnitine

The most widely investigated aspect of carnitine is the carnitine-dependent transport of fats to the intermitochondrial membrane; however, some other established roles include the preservation of membrane integrity, stabilization of a physiologic coenzyme A:acetyl-CoA ratio in the mitochondria, and the reduction of lactate production.78

Carnitine serves as a cofactor for several enzymes, including carnitine translo-case and acylcarnitine transferases I and II, which are essential for the movement of activated long-chain fatty acids from the cytoplasm into the mitochondria (Figure 11.2). The translocation of fatty acids (FAs) is critical for the generation of adenosine triphosphate (ATP) within skeletal muscle, via ^-oxidation. These activated FAs become esterified to acylcarnitines with carnitine via carnitine-acyl-transferase I (CAT I) in the outer mitochondrial membrane. Acylcarnitines can easily permeate the membrane of the mitochondria and are translocated across the membrane by carnitine translocase. Carnitine's actions are not yet complete because the mitochondrion has two membranes to cross; thus, through the action of CAT II, the acylcar-nitines are converted back to acyl-CoA and carnitine. Acyl-CoA can be used to generate ATP via ^-oxidation, Krebs cycle, and the electron transport chain. Car-nitine is recycled to the cytoplasm for future use.

As previously mentioned, carnitine has a unique interaction with acyl-CoA in the mitochondria and is an important modulator of the acyl-CoA:free CoA ratio. This is demonstrated when acylcarnitines are formed. This relationship is defined by the rate of acyl-CoA production: if the acyl-CoAs are produced more rapidly than they are used, then the acyl-CoA within the intramitochondrial space is high compared to the free CoA concentration.910 This imbalance can then be corrected because carnitine can bind the acyl-CoAs and the once elevated ratio can return to normal. The regulation of this ratio and the interaction of carnitine with acetyl-CoA may suppress the production of lactic acid during high-intensity exercise, primarily because it acts to inhibit the downregulation of the pyruvate dehydrogenase (PDH) caused by the increase in acetyl-CoA.11

Outer mitochondrial membrane

Inter membrane space

Fatty Acid

Outer mitochondrial membrane

Carnitine

Inter membrane space

Carnitine

Carnitine/acyl t

Carnitine/acyl t

Carnitine

Carnitine

Fatty acyl-carnitine

Inner mitochondrial membrane

Mitochondrial matrix

Fatty acyl-CoA

Fatty acyl-CoA

ß-oxidation

FIGURE 11.2 Roles of carnitine in the movement of long chain fatty acids into the mitochondrial matrix.

It is important to differentiate the two forms of carnitine, which are L-carnitine and D-carnitine (Dextro form). L-carnitine is the physiologically active form and is endogenously produced within the human, whereas D-carnitine is not physiologically active and is a synthetic.12 Research has shown that subjects given D-carnitine saw a depletion of their endogenous stores of L-carnitine,1314 which may manifest itself as carnitine deficiency, especially during intense bouts of exercise.15 Supplementation of D-carnitine is therefore not recommended because it may have a deleterious effect on the body as well as performance.

Carnitine plays a major role in substrate metabolism in healthy individuals, but there are individuals who have carnitine deficiencies, and in these individuals carnitine supplementation can be utilized as a therapeutic agent. Typically the daily average American diet has about 100 to 300 mg of carnitine.16 The primary sources of carnitine are found in red meat and dairy products, whereas vegetables have very little L-carnitine; thus, vegetarian diets may contain miniscule amounts. Despite adequate intake of carnitine by the majority of the population, there is still a fraction of the population who have carnitine disturbances. This may be due to several metabolic abnormalities, which include defective carnitine synthesis, enhanced carnitine degradation, impaired transport of carnitine whether it is in or out of cells, and finally abnormal renal handling of carnitine.1718 These abnormalities manifest in a syndrome known as primary carnitine deficiency, the myopathic form having symptoms such as muscle fatigue, cramps, hypotona, and atrophy of the musculature, and the systemic form, the more severe form, having symptoms such as nausea, vomiting, and coma due to excessive fat storage because of reduced hepatic efficiency.19-21

Carnitine supplementation in these states has proven effective. For example, in cardiac diseases, the myocardium uses fatty acids as its primary source of fuel; therefore, a deficiency in carnitine may have a serious impact on heart rate and stroke volume and thus cardiac output. In fact, most research on these types of cardiac patients supports the use of carnitine as a supplement and furthermore has found that abnormal fatty acid metabolism is normalized.22-25 The focus of this chapter, however, will be the effects and efficacy of carnitine supplementation in healthy populations, specifically as a potential ergogenic aid to athletic performance.

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