Carnitine: Metabolism and clinical chemistry

Siliprandi, N.; Sartorelli, L.; Ciman, M.; Lisa, Fabio Di

doi:10.1016/0009-8981(89)90267-2

Cited by 87 publications

(32 citation statements)

References 31 publications

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“…Chitosan may act as a bile acid-sequestering agent that reduces cholesterol by interrupting enterohepatic circulation (Parra-Barraza et al, 2005). Vitamin C is essential for the synthesis of muscle carnitine (Hulse et al, 1978), a small molecule responsible for shuttling long chain fatty acids across the mitochondrial membrane for β-oxidation, subsequent fat oxidation and energy production (Siliprandi et al, 1989;Reda et al, 2003). Thus, the vitamin C status may represent a modifi able condition that might impact the expression of the obesity phenotype (Johnston, 2005).…”

Section: Discussionmentioning

confidence: 97%

Vitamin C increases the fecal fat excretion by chitosan in guinea‐pigs, thereby reducing body weight gain

Jun

Jung

Kang

et al. 2010

Phytotherapy Research

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The aims of this study were to investigate the antiobesity properties of chitosan on its own, as well as in the presence of vitamin C, in vivo. Hartley guinea-pigs were divided into Control (normal diet), F-control (high fat diet), Chitosan (high fat diet with 5.0% chitosan) and Chito-vit C (high fat diet with 5.0% chitosan containing 0.5% vitamin C) groups, respectively. The effects of chitosan, both alone and in the presence of vitamin C, on body weight, total fecal weight, fecal composition and plasma lipid level were studied for 5 weeks. The results of this study indicated that the fat-binding and water-holding capacity of chitosan might decrease body weight by reducing the absorption of cholesterol and fat, subsequently increasing total fecal weight, fecal fat excretion and fecal water excretion. Vitamin C increased the fecal fat excretion by chitosan in guinea-pigs, thereby reducing body weight gain.

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Section: Discussionmentioning

confidence: 97%

Vitamin C increases the fecal fat excretion by chitosan in guinea‐pigs, thereby reducing body weight gain

Jun

Jung

Kang

et al. 2010

Phytotherapy Research

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“…In vesicles preloaded with butyrobetaine, carnitine transport was significantly inhibited, indicating that there is no exchange mechanism between carnitine and butyrobetaine under the conditions used in our studies. Such an exchange mechanism has been postulated based on studies using isolated rat skeletal muscle [45,46] and in in vivo studies in rats [47]. Of course the possibility cannot be excluded that such an exchanger exists in other types of skeletal muscle, heart or other organs.…”

Section: Discussionmentioning

confidence: 99%

Characterization of L‐carnitine transport into rat skeletal muscle plasma membrane vesicles

Berardi¹,

Stieger²,

Hagenbuch³

et al. 2000

European Journal of Biochemistry

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Transport of l-carnitine into skeletal muscle was investigated using rat sarcolemmal membrane vesicles. In the presence of an inwardly directed sodium chloride gradient, l-carnitine transport showed a clear overshoot. The uptake of l-carnitine was increased, when vesicles were preloaded with potassium. When sodium was replaced by lithium or cesium, and chloride by nitrate or thiocyanate, transport activities were not different from in the presence of sodium chloride. However, l-carnitine transport was clearly lower in the presence of sulfate or gluconate, suggesting potential-dependent transport. An osmolarity plot revealed a positive slope and a significant intercept, indicating transport of l-carnitine into the vesicle lumen and binding to the vesicle membrane. Displacement experiments revealed that approximately 30% of the l-carnitine associated with the vesicles was bound to the outer and 30% to the inner surface of the vesicle membrane, whereas 40% was unbound inside the vesicle. Saturable transport could be described by Michaelis±Menten kinetics with an apparent K m of 13.1 mm and a V max of 2.1 pmol´(mg protein 21 )´s 21 . l-Carnitine transport could be trans-stimulated by preloading the vesicles with l-carnitine but not with the carnitine precursor butyrobetaine, and was cis-inhibited by l-palmitoylcarnitine, l-isovalerylcarnitine, and glycinebetaine. On comparing carnitine transport into rat kidney brush-border membrane vesicles and OCTN2, a sodium-dependent high-affinity human carnitine transporter, cloned recently from human kidney also expressed in muscle, the K m values are similar but driving forces, pattern of inhibition and stereospecificity are different. This suggests the existence of more than one carnitine carrier in skeletal muscle.

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“…Therefore, many tissues like skeletal and heart muscle are highly dependent on active carnitine uptake from blood. 11 Consequently, the rare syndrome of hereditary systemic carnitine deficiency, which results from several mutations in the OCTN2 gene, leads, among other symptoms, to severe cardiomyopathy, which indicates an important physiological function of OCTN2 for the human heart. 12 In addition to these physiological functions, OCTN2 is of potential pharmacological relevance, because several drugs such as ␤-lactam antibiotics and valproic acid have been described as substrates of OCTN2 or inhibitors of carnitine transport.…”

Section: Clinical Perspective P 1122mentioning

confidence: 99%

Uptake of Cardiovascular Drugs Into the Human Heart

et al. 2006

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Background-To date, the uptake of drugs into the human heart by transport proteins is poorly understood. A candidate protein is the organic cation transporter novel type 2 (OCTN2) (SLC22A5), physiologically acting as a sodiumdependent transport protein for carnitine. We investigated expression and localization of OCTN2 in the human heart, uptake of drugs by OCTN2, and functional coupling of OCTN2 with the eliminating ATP-binding cassette (ABC) transporter ABCB1 (P-glycoprotein). Methods and Results-Messenger RNA levels of OCTN2 and ABCB1 were analyzed in heart samples by quantitative polymerase chain reaction. OCTN2 was expressed in all auricular samples that showed a pronounced interindividual variability (35 to 1352 copies per 20 ng of RNA). Although a single-nucleotide polymorphism in OCTN2 (G/C at position Ϫ207 of the promoter) had no influence on expression, administration of ␤-blockers resulted in significantly increased expression. Localization of OCTN2 by in situ hybridization, laser microdissection, and immunofluorescence microscopy revealed expression of OCTN2 mainly in endothelial cells. For functional studies, OCTN2 was expressed in Madin-Darby canine kidney (MDCKII) cells. Using this system, verapamil, spironolactone, and mildronate were characterized both as inhibitors (EC 50 ϭ25, 26, and 21 mol/L, respectively) and as substrates. Like OCTN2, ABCB1 was expressed preferentially in endothelial cells. A significant correlation of OCTN2 and ABCB1 expression in the human heart was observed, which suggests functional coupling. Therefore, the interaction of OCTN2 with ABCB1 was tested with double transfectants. This approach resulted in a significantly higher transcellular transport of verapamil, a substrate for both OCTN2 and ABCB1. Conclusions-OCTN2 is expressed in the human heart and can be modulated by drug administration. Moreover, OCTN2can contribute to the cardiac uptake of cardiovascular drugs.

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Carnitine: Metabolism and clinical chemistry

Cited by 87 publications

References 31 publications

Vitamin C increases the fecal fat excretion by chitosan in guinea‐pigs, thereby reducing body weight gain

Vitamin C increases the fecal fat excretion by chitosan in guinea‐pigs, thereby reducing body weight gain

Characterization of L‐carnitine transport into rat skeletal muscle plasma membrane vesicles

Uptake of Cardiovascular Drugs Into the Human Heart

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