L-carnitine: Dietary Sources and Endogenous Synthesis
Jun 12,2024
General Description
L-Carnitine, essential for energy metabolism, is crucial for maintaining homeostasis. While synthesis occurs internally, dietary intake, primarily from animal products, plays a significant role. Endogenous synthesis involves a complex process relying on essential amino acids and specific organs such as the liver, kidneys, and brain. Enzymes catalyze various steps to convert precursors into L-carnitine, with the liver, kidney, and brain playing key roles. Understanding dietary sources and endogenous synthesis mechanisms is essential for ensuring optimal levels of L-carnitine for metabolic function and overall health. Strict vegetarians and individuals with increased demands may benefit from supplementation.
Figure 1. L-carnitine
Dietary Sources
L-Carnitine, an essential compound for energy metabolism, is primarily obtained through dietary sources. Over 90% of the body's carnitine pool resides in skeletal and myocardial muscles, with smaller amounts found in the liver, kidneys, and other tissues. Skeletal muscles serve as the main reservoir, containing concentrations of L-carnitine significantly higher than in blood plasma. While the body can synthesize L-carnitine internally, dietary intake plays a crucial role in maintaining carnitine homeostasis, especially during periods of stress or physical exertion. The daily requirement for L-carnitine is approximately 15 mg, with the average adult synthesizing 11 to 34 mg per day. However, certain conditions such as intense physical training or specific medical conditions may increase the demand for L-carnitine, necessitating supplementation. The primary dietary sources of L-carnitine are animal products, particularly red meat such as lamb and beef. Fish, pork, poultry, and dairy products also contribute to carnitine intake, albeit to a lesser extent. Plant-based foods generally contain negligible amounts of carnitine, with the exception of avocado and asparagus, which contain noteworthy levels. It's important to note that food processing methods, such as boiling, can leach significant amounts of L-carnitine from tissues, potentially reducing its content in cooked foods. Overall, a balanced omnivorous diet typically provides around 75% of the daily carnitine requirement, with the remaining 25% synthesized endogenously. However, strict vegetarians may be at risk of L-carnitine deficiency due to the absence of carnitine in plant-based protein sources. Individuals with specific medical conditions or increased physiological demands may benefit from targeted L-carnitine supplementation to support optimal metabolic function and overall health. 1
Endogenous Synthesis
In mammals, L-carnitine, a vital compound for energy metabolism, is primarily synthesized endogenously in specific organs such as the liver, kidneys, and in certain species, the testes and brain. This biosynthesis process predominantly relies on essential amino acids lysine and methionine as precursors, ultimately forming trimethyllysine (TML), which serves as an intermediate in carnitine production. The availability of TML plays a crucial role in regulating carnitine biosynthesis, with skeletal muscle protein turnover serving as a rate-limiting step. Lysine provides the carbon skeleton for carnitine, while methyl groups are derived from methionine. This process involves post-translational modifications, including lysine methylation catalyzed by lysine methyltransferase, with S-adenosyl-L-methionine (SAM) serving as a methyl group donor. Following lysosomal hydrolysis, TML residues are released and hydroxylated to form 3-hydroxytrimethyllysine (HTML) by mitochondrial dioxygenase TML (TMLD). Subsequent steps include cleaving HTML to glycine and 4-trimethylaminobutyraldehyde (TMABA) catalyzed by HTML aldolase (HTMLA), and dehydrogenation of TMABA to form butyrobetaine (BB) catalyzed by TMABA dehydrogenase (TMABA DH). The final step involves the hydroxylation of butyrobetaine to carnitine, facilitated by butyrobetaine dioxygenase (BBD), which requires iron ion and ascorbate as cofactors. The expression of BBD varies during development, with low levels at birth gradually increasing to adult values. Notably, BBD activity is primarily found in the liver, kidney, and brain, indicating that these organs are crucial for the final conversion of butyrobetaine to L-carnitine in humans. While enzymes involved in carnitine synthesis are generally located in the cytosol, TMLD occurs in the mitochondria. Although enzymes such as TMLD, HTMLA, and TMABA dehydrogenase are tissue non-specific, BBD is strictly localized in specific tissues, emphasizing the importance of the liver, kidney, and brain in the endogenous synthesis of L-carnitine. 2
Reference
1. Pekala J, Patkowska-Sokoła B, Bodkowski R, et al. L-carnitine--metabolic functions and meaning in humans life. Curr Drug Metab. 2011; 12(7): 667-678.
2. Vaz F M, Wanders RJ. Carnitine biosynthesisi in mammals. Biochem J. 2002; 61: 417-429.
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