Disease relevance of Carnitine

• L-carnitine for treatment of distal ulcerative colitis [1].
• L-carnitine for leg ulcers [2].
• Increases in walking distance in patients with peripheral vascular disease treated with L-carnitine: a double-blind, cross-over study [3].
• More importantly, we demonstrate in vivo and in vitro the effectiveness of a strategy for preventing drug-induced hearing loss using l-carnitine (LCAR), a safe micronutrient that plays a key role in energy metabolism and detoxification [Rebouche, C. J. & Seim, H. (1998) Annu. Rev. Nutr. 18, 39-61] [4].
• No toxicity related to L-carnitine therapy was observed and dose reductions were not necessary [5].

Psychiatry related information on Carnitine

• On a molar basis, this beneficial effect is greater than that observed with L-carnitine and, thus, the findings of the present study may have clinical relevance in terms of treatment cost and patient compliance [6].
• These results suggest that acetyl levocarnitine may retard the deterioration in some cognitive areas in patients with Alzheimer's disease and stress the need for a larger study of this drug [7].
• The present study demonstrates that oral administration of L-carnitine prior to disease onset significantly delayed the onset of signs of disease (log-rank P=0.0008), delayed deterioration of motor activity, and extended life span (log-rank P=0.0001) in transgenic mice carrying a human SOD1 gene with a G93A mutation (Tg) [8].
• A time/response study (PTZ was injected 1, 5, 15 or 30 min after L-carnitine) showed that the anticonvulsive effects were apparent when the interval between L-carnitine and PTZ administration was 15-30 min [9].
• Medium-term open label trial of L-carnitine in Rett syndrome [10].

High impact information on Carnitine

• Carnitine is synthesized in most eucaryotic organisms, although a few insects (and most likely some newborn animals) require it as a nutritional factor (vitamin BT) [11].
• The half-life of plasma carnitine for cystinotic children given a single oral dose approximated 6.3 h; 14% of ingested L-carnitine was excreted within 24 h [12].
• We suggest that L-carnitine may be a useful therapeutic approach for elimination of toxic acyl CoA compounds in several of these disorders [13].
• Our results also suggested that a calmodulin- but not a protein kinase C- or protein kinase A-mediated pathway plays a role in regulating L-carnitine uptake by Caco-2 cells [14].
• CONCLUSIONS: L-carnitine uptake by intestinal epithelial cells (Caco-2) involves a carrier-mediated system that is temperature-, Na(+)-, and energy-dependent and seems to be under the regulation of a calmodulin-mediated pathway [14].

Chemical compound and disease context of Carnitine

• CaiT of Escherichia coli, a new transporter catalyzing L-carnitine/gamma -butyrobetaine exchange [15].
• Control and streptozocin-induced diabetic (STZ-D) rats were treated daily for 6 wk with high-dose L-carnitine (3 g.kg-1.day-1 i.p.). STZ-D results in loss of body weight and hypoinsulinemia [16].
• This represents the first instance in which a nonnaturally occurring analogue of l-carnitine has been shown to undergo transport via this mitochondrial translocase, suggesting the possibility that cyclic carnitine analogues may find utility as agents in the treatment of myocardial ischemia [17].
• The percentage area of necrosis, fibrosis, and calcification in the L-carnitine and verapamil groups was significantly smaller than that in the saline group [18].
• In order to investigate the importance of modulated lipid metabolism and alterations in mitochondrial properties in this cell death process, we incubated glioma cells both with TTA and the oxidizable fatty acid palmitic acid (PA), in the presence of L-carnitine and the carnitine palmitoyltransferase inhibitors etomoxir and aminocarnitine [19].

Biological context of Carnitine

• Effect of L-carnitine on human immunodeficiency virus-1 infection-associated apoptosis: a pilot study [5].
• PC, but neither palmitic acid nor DL-carnitine, inhibited the TPA-induced cell adhesion and morphological changes with the median inhibitory concentration of 1 microM, whereas a TPA-induced increase in acid phosphatase activity was not affected by 3 microM PC [20].
• Juvenile visceral steatosis (JVS) mice, which show systemic L-carnitine deficiency, may be an animal model of Reye's syndrome because of its phenotype of fat deposition and mitochondrial abnormalities in the liver [21].
• The kinetics of purified beef heart mitochondrial carnitine palmitoyltransferase have been extensively investigated with a semiautomated system and the computer program TANKIN and shown to be sigmoidal with both acyl-CoA and L-carnitine [22].
• Effect of L-carnitine treatment on lipid metabolism and cardiac performance in chronically diabetic rats [16].

Anatomical context of Carnitine

• These studies demonstrate the presence of an active intestinal transport system for L-carnitine in human intestinal mucosa [23].
• L-carnitine therapy also led to a drop in the frequency of apoptotic CD4 and CD8 lymphocytes [5].
• Loss of wild-type carrier-mediated L-carnitine transport activity in hepatocytes of juvenile visceral steatosis mice [21].
• Among these latter mutants, three were deleted for genes involved in plasma membrane transport, including the L-carnitine transporter Agp2, as well as the kinases Ptk2 and Sky1, which are involved in regulating polyamine transport [24].
• However, L-carnitine did not protect cardiac myocytes from apoptosis induced by exogenous cell-permeant ceramide [25].

Associations of Carnitine with other chemical compounds

• Carnitine acetyltransferase catalyzes the interchange between L-carnitine and acetyl-L-carnitine [26].
• The effects of L-carnitine on myocardial glycolysis, glucose oxidation, and palmitate oxidation were determined in isolated working rat hearts [27].
• L-Carnitine increased pyruvate metabolism 3- to 4-fold and allowed limited rates of oxidative phosphorylation [28].
• In contrast, stearic acid beta-oxidation by purified mitochondria depended upon exogenous L-carnitine, and the oxidation was stimulated by L-malate [29].
• A more empirical approach, based on cross-referencing substrate structure comparisons with protein alignment data, was used to redesign choline acetyltransferase to accommodate L-carnitine as an acceptor of the acetyl group [30].

Gene context of Carnitine

• Here, we report the first detailed functional characterization of the caiT gene product, a putative transport protein whose function is required for l-carnitine conversion in Escherichia coli [15].
• The gene YAT1 from Saccharomyces cerevisiae encodes a protein of 688 amino acids which displays significant sequence similarity to vertebrate L-carnitine acyltransferases and yeast inner mitochondrial L-carnitine acetyltransferase [31].
• This impairment of l-carnitine transport by OCTN1 may respond to high-dose l-carnitine therapy [32].
• The results showed that, except from infertility, L-carnitine treatment resulted in a significant increase of macrophages and to a lesser degree an increase of T-cells, while elevated levels of IFN-gamma and TNF-alpha were detected in both serum and peritoneal fluid compared to controls [33].
• Under these conditions, an E. coli K-12 strain with lesions in both proP and proU accumulates low levels of L-carnitine but fails to accumulate betaine when these compounds are supplied in the external medium [34].

Analytical, diagnostic and therapeutic context of Carnitine

• After treatment with oral L-carnitine, 100 mg/kg per d divided every 6 h, plasma carnitine concentrations became normal in all subjects within 2 d [12].
• Treatment with L-carnitine alone has proven effective in preventing further hospitalizations in a patient with this genetic disorder [35].
• A systematic review is here performed to determine the effects of L-carnitine in maintenance hemodialysis patients [36].
• Substrate kinetics were determined by use of [1-14C]palmitate, [3,4-13C2]-acetoacetate, [6,6-2H2]glucose, and [5,5,5-2H3]leucine before and during a 3-h intravenous infusion of L-carnitine [37].
• Plasma samples were analyzed for L-carnitine, acetyl-L-carnitine, and total carnitine by HPLC [38].

References