Carnitine biosynthesis in mammals

Vaz, Frédéric M.; Wanders, Ronald J. A.

doi:10.1042/0264-6021:3610417

Cited by 448 publications

(390 citation statements)

References 159 publications

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“…Expression of Genes Involved in Carnitine Biosynthesis and Transport-L-Carnitine is a quaternary amine obtained from dietary sources or synthesized endogenously from trimethylated lysine residues derived from protein degradation (19). Because the liver is the principal site of carnitine biosynthesis in rats, we proceeded to examine hepatic expression of genes involved in carnitine homeostasis (Fig.…”

Section: Carnitine Homeostasis Is Compromised By Chronicmentioning

confidence: 99%

Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control

Noland¹,

Koves²,

Seiler³

et al. 2009

Journal of Biological Chemistry

282

327

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In addition to its essential role in permitting mitochondrial import and oxidation of long chain fatty acids, carnitine also functions as an acyl group acceptor that facilitates mitochondrial export of excess carbons in the form of acylcarnitines. Recent evidence suggests carnitine requirements increase under conditions of sustained metabolic stress. Accordingly, we hypothesized that carnitine insufficiency might contribute to mitochondrial dysfunction and obesity-related impairments in glucose tolerance. Consistent with this prediction whole body carnitine dimunition was identified as a common feature of insulin-resistant states such as advanced age, genetic diabetes, and diet-induced obesity. In rodents fed a lifelong (12 month) high fat diet, compromised carnitine status corresponded with increased skeletal muscle accumulation of acylcarnitine esters and diminished hepatic expression of carnitine biosynthetic genes. Diminished carnitine reserves in muscle of obese rats was accompanied by marked perturbations in mitochondrial fuel metabolism, including low rates of complete fatty acid oxidation, elevated incomplete ␤-oxidation, and impaired substrate switching from fatty acid to pyruvate. These mitochondrial abnormalities were reversed by 8 weeks of oral carnitine supplementation, in concert with increased tissue efflux and urinary excretion of acetylcarnitine and improvement of whole body glucose tolerance. Acetylcarnitine is produced by the mitochondrial matrix enzyme, carnitine acetyltransferase (CrAT). A role for this enzyme in combating glucose intolerance was further supported by the finding that CrAT overexpression in primary human skeletal myocytes increased glucose uptake and attenuated lipid-induced suppression of glucose oxidation. These results implicate carnitine insufficiency and reduced CrAT activity as reversible components of the metabolic syndrome.Disturbances in mitochondrial genesis, morphology, and function are increasingly recognized as components of insulin resistance and the metabolic syndrome (1-3). Still unclear is whether poor mitochondrial performance is a predisposing factor or a consequence of the disease process. The latter view is supported by recent animal studies linking diet-induced insulin resistance to a dysregulated mitochondrial phenotype in skeletal muscle, marked by excessive ␤-oxidation, impaired substrate switching during the fasted to fed transition, and coincident reduction of organic acid intermediates of the tricarboxylic acid cycle (4, 5). In these studies, both diet-induced and genetic forms of insulin resistance were specifically linked to high rates of incomplete fat oxidation and intramuscular accumulation of fatty acylcarnitines, byproducts of lipid catabolism that are produced under conditions of metabolic stress (5, 6). Most compelling, we showed that genetically engineered inhibition of fat oxidation lowered intramuscular acylcarnitine levels and preserved glucose tolerance in mice fed a high fat diet (5, 7). In aggregate, the findings established a stron...

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Section: Carnitine Homeostasis Is Compromised By Chronicmentioning

confidence: 99%

Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control

Noland¹,

Koves²,

Seiler³

et al. 2009

Journal of Biological Chemistry

282

327

View full text Add to dashboard Cite

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“…It is essential in the control of carbohydrate-lipid metabolic capacity, the formation of cell membrane structure, cellular vitality, the prevention of free oxygen radical formation, scavenging of free radicals, and protection of cells from peroxidative stress 11 . The body can endogenously synthesize about 10% of the L-carnitine it requires from lysine and methionine amino acids in the skeletal muscle, heart, liver, kidney, and brain; the remaining amount is generally obtained through diet 12,13 . Experimental models have demonstrated its radioprotective effects in the kidney, lens and cochlea, retina, brain, growing bone, testes, oral mucosa, small intestine and bone marrow [14][15][16][17][18][19][20][21] .…”

Section: Introductionmentioning

confidence: 99%

L-carnitine has a protective effect on the colonic mucosa during abdominopelvic radiotherapy in rats

et al. 2016

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PURPOSE:To evaluate histopathologically the radioprotective effect of L-carnitine on the colonic mucosa in rats undergoing abdominopelvic irradiation. METHODS:Thirty-two rats were randomly assigned to four experimental groups: intraperitoneal administration of normal saline (group 1) or L-carnitine (300 mL/kg; group 2), followed in groups 3 and 4, respectively, by one dose of abdominopelvic radiation (20 Gy) 30 min later. Rats were sacrificed 5 days after radiation, and their descending colons were resected for histopathological evaluation of the presence and severity of damage. RESULTS:Average damage scores did not differ significantly between groups 1 and 2 (0.13 ± 0.35 and 0.25 ± 0.46, respectively); the group 3 score was highest (10.25 ± 0.71), and the group 4 score (3.63 ± 1.41) was significantly lower than that of group 3 (both p = 0.0001). Pre-radiation L-carnitine administration significantly reduced mucosal thinning, crypt distortion, reactive atypia, inflammation, cryptitis, and reactive lymph-node hyperplasia (all p < 0.01).CONCLUSIONS: L-carnitine had a radioprotective effect on rat colonic mucosa. L-carnitine use should be explored for patients with gastrointestinal cancer, who have reduced serum L-carnitine levels.

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“…L-carnitine plays an important role in intermediary metabolism, including the transport of long chain fatty acids across the mitochondrial inner membrane (Vaz and Wanders 2002;Bain et al 2006). L-carnitine is an essential cofactor in the β-oxidation of long-chain fatty acids.…”

mentioning

confidence: 99%

“…butyrate) is an endogenous compound derived from the diet, such as meat and dairy products, or being synthesized in the liver or kidneys from the essential amino acids lysine and methionine (Vaz and Wanders 2002;Bain et al 2006;Tsakiris et al 2008). L-carnitine plays an important role in intermediary metabolism, including the transport of long chain fatty acids across the mitochondrial inner membrane (Vaz and Wanders 2002;Bain et al 2006).…”

mentioning

confidence: 99%

Single Dose Administration of L-Carnitine Improves Antioxidant Activities in Healthy Subjects

Cao

et al. 2011

Tohoku J. Exp. Med.

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L-carnitine has been used as a supplement to treat cardiovascular or liver disease. However, there has been little information about the effect of L-carnitine on anti-oxidation capability in healthy human subjects. This study was designed to investigate the correlation between plasma L-carnitine concentration and antioxidant activity. Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma concentration of L-carnitine was detected by HPLC. The baseline concentration of L-carnitine was 39.14 ± 5.65 μmol/L. After single oral administration, the maximum plasma concentration (C max ) and area under the curve (AUC 0-∞ ) were 84.7 ± 25.2 μmol/L and 2,676.4 ± 708.3 μmol/L·h, respectively. The half-life and the time required to reach the C max was 60.3 ± 15.0 min and 3.4 ± 0.46 h, respectively. There was a gradual increase in plasma concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and total antioxidative capacity (T-AOC) in the first 3.5 h following L-carnitine administration. The plasma concentrations of SOD, GSH-Px, catalase and T-AOC returned to baseline levels within 24 h. A positive correlation was found between L-carnitine concentration and the antioxidant index of SOD (r = 0.992, P < 0.01), GSH-Px (r = 0.932, P < 0.01), catalase (r = 0.972, P < 0.01) or T-AOC (r = 0.934, P < 0.01). In conclusion, L-carnitine increases activities of antioxidant enzymes and the total antioxidant capacity in healthy subjects. It may be useful as a supplementary therapy for chronic illnesses involving excessive oxidative stress.

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Carnitine biosynthesis in mammals

Cited by 448 publications

References 159 publications

Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control

Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control

L-carnitine has a protective effect on the colonic mucosa during abdominopelvic radiotherapy in rats

Single Dose Administration of L-Carnitine Improves Antioxidant Activities in Healthy Subjects

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