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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