2013年10月21日星期一

How to get L-carnitine?

L-carnitine is a derivative of the amino acid, lysine. Its name is derived from the fact that it was first isolated from meat  in 1905. Only the L-isomer of carnitine is biologically active . L-carnitine appeared to act as a vitamin in the mealworm and was therefore termed vitamin BT . Vitamin BT, however, is actually a misnomer because humans and other higher organisms can synthesize L-carnitine . Under certain conditions, the demand for L-carnitine may exceed an individual's capacity to synthesize it, making it a conditionally essential micronutrient .


1. Endogenous Biosynthesis

Humans can synthesize L-carnitine(CAS.NO:541-15-1) from the amino acids lysine and methionine in a multi-step process. Specifically, protein-bound lysine is enzymatically methylated to form episilon-N-trimethyllysine ;  three molecules of methionine provide the methyl groups for the reaction. Epsilon-N-trimethyllysine is released for carnitine synthesis by protein hydrolysis . Several enzymes are involved in endogenous L-carnitine biosynthesis. The enzyme gamma-butyrobetaine hydroxylase, however, is absent from cardiac and skeletal muscle but highly expressed in human liver, testes, and kidney . The rate of L-carnitine biosynthesis in humans was studied in vegetarians and is estimated to be 1.2 micromol/kg of body weight/day . Changes in dietary carnitine intake or renal reabsorption do not appear to affect the rate of endogenous carnitine synthesis .

2. Absorption of Exogenous L-Carnitine

1)Dietary L-Carnitine

The bioavailability of L-carnitine from food can vary depending on dietary composition. For instance, one study reported that bioavailability of L-carnitine in individuals adapted to low-carnitine diets (i.e., vegetarians; 66%-86%) is higher than those adapted to high-carnitine diets (i.e., regular red meat eaters; 54%-72%) .

2)L-Carnitine Supplements

While bioavailability of L-carnitine from the diet is quite high , absorption from oral L-carnitine supplements is considerably lower. According to one study, bioavailability of L-carnitine from oral supplements (0.5-6 gram dosage) ranges from 14%-18% of the total dose . Less is known regarding the metabolism of the acetylated form of L-carnitine, acetyl-L-carnitine (ALCAR); however, bioavailability of ALCAR is thought to be higher than L-carnitine. The results of in vitro experiments suggest that ALCAR is partially hydrolyzed upon intestinal absorption . In humans, administration of 2 grams of ALCAR per day for 50 days increased plasma ALCAR levels by 43%, suggesting that some acetyl-L-carnitine is absorbed without hydrolysis or that L-carnitine is reacetylated in the enterocyte .
3)Elimination and Reabsorption


L-carnitine and short-chain acylcarnitines (esters of L-carnitine), such as acetyl-L-carnitine, are excreted by the kidneys. Renal reabsorption of L-carnitine is normally very efficient; in fact, an estimated 95% is thought to be reabsorbed by the kidneys . Therefore, carnitine excretion by the kidney is normally very low. However, several conditions can decrease carnitine reabsorption efficiency and, correspondingly, increase carnitine excretion. Such conditions include high-fat (low-carbohydrate) diets, high-protein diets, pregnancy, and certain disease states (see Primary Systemic Carnitine Deficiency) . In addition, when circulating L-carnitine levels increase, as in the case of oral supplementation, renal reabsorption of L-carnitine becomes saturated, resulting in increased urinary excretion of L-carnitine . Dietary or supplemental L-carnitine that is not absorbed by enterocytes is degraded by colonic bacteria to form two principal products, trimethylamine and gamma-butyrobetaine. Gamma-butyrobetaine is eliminated in the feces; trimethylamine is efficiently absorbed and metabolized to trimethylamine-N-oxide, which is excreted in the urine .

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