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Carnitine and Acylcarnitines

Pharmacokinetic, Pharmacological and Clinical Aspects

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Abstract

L-Carnitine (levocarnitine) is a naturally occurring compound found in all mammalian species. The most important biological function of L-carnitine is in the transport of fatty acids into the mitochondria for subsequent β-oxidation, a process which results in the esterification of L-carnitine to form acylcarnitine derivatives. As such, the endogenous carnitine pool is comprised of L-carnitine and various short-, medium-and long-chain acylcarnitines.

The physiological importance of L-carnitine and its obligatory role in the mitochondrial metabolism of fatty acids has been clearly established; however, more recently, additional functions of the carnitine system have been described, including the removal of excess acyl groups from the body and the modulation of intracellular coenzyme A (CoA) homeostasis. In light of this, acylcarnitines cannot simply be considered by-products of the enzymatic carnitine transfer system, but provide indirect evidence of altered mitochondrial metabolism. Consequently, examination of the contribution of L-carnitine and acylcarnitines to the en-dogenous carnitine pool (i.e. carnitine pool composition) is critical in order to adequately characterize metabolic status.

The concentrations of L-carnitine and its esters are maintained within relatively narrow limits for normal biological functioning in their pivotal roles in fatty acid oxidation and maintenance of free CoA availability. The homeostasis of carnitine is multifaceted with concentrations achieved and maintained by a combination of oral absorption, de novo biosynthesis, carrier-mediated distribution into tissues and extensive, but saturable, renal tubular reabsorption.

Various disorders of carnitine insufficiency have been described but ultimately all result in impaired entry of fatty acids into the mitochondria and consequently disturbed lipid oxidation. Given the sensitivity of acylcarnitine concentrations and the relative carnitine pool composition in reflecting the intramitochondrial acyl-CoA to free CoA ratio (and, hence, any disturbances in mitochondrial metabolism), the relative contribution of L-carnitine and acylcarnitines within the total carnitine pool is therefore considered critical in the identification of mitochondria dysfunction. Although there is considerable research in the literature focused on disorders of carnitine insufficiency, relatively few have examined relative carnitine pool composition in these conditions; consequently, the complexity of these disorders may not be fully understood. Similarly, although important studies have been conducted establishing the pharmacokinetics of exogenous carnitine and short-chain carnitine esters in healthy volunteers, few studies have examined carnitine pharmacokinetics in patient groups. Furthermore, the impact of L-carnitine administration on the kinetics of acylcarnitines has not been established.

Given the importance of L-carnitine as well as acylcarnitines in maintaining normal mitochondrial function, this review seeks to examine previous research associated with the homeostasis and pharmaco-kinetics of L-carnitine and its esters, and highlight potential areas of future research.

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References

  1. Gulewitsch W, Krimberg R. Zur kenntnis der extraktivstoffe der muskeln. II. Mitteilung. Über das carnitin. Hoppe-Seyler’s Z Physiol Chem 1905; 45(3–4): 326–30

    Article  CAS  Google Scholar 

  2. Tomita M, Sendju Y. Über die oxyaminoverbindungen, welche die biuretreaktion zeigen. III. Spaltung der γ-amino-β-oxy-buttersäure in die optischaktiven komponenten. Hoppe-Seyler’s Z Physiol Chem 1927; 169(4–6): 263–77

    Article  CAS  Google Scholar 

  3. Fritz I. The effect of muscle extracts on the oxidation of palmitic acid by liver slices and homogenates. Acta Physiol Scand 1955; 34(4): 367–85

    Article  PubMed  CAS  Google Scholar 

  4. Friedman S, Fraenkel G. Reversible enzymatic acetylation of carnitine. Arch Biochem Biophys 1955; 59(2): 491–501

    Article  PubMed  CAS  Google Scholar 

  5. Carter HE, Bhattacharyya PK, Weidman KR, et al. Chemical studies on vitamin BT isolation and characterization as carnitine. Arch Biochem Biophys 1952; 38: 405–16

    Article  PubMed  CAS  Google Scholar 

  6. Bremer J. Carnitine: metabolism and functions. Physiol Rev 1983; 63(4): 1420–80

    PubMed  CAS  Google Scholar 

  7. Bahl JJ, Bressler R. The pharmacology of carnitine. Annu Rev Pharmacol Toxicol 1987; 27: 257–77

    Article  PubMed  CAS  Google Scholar 

  8. Choi YR, Fogle PJ, Clarke PR, et al. Quantitation of water-soluble acylcarnitines and carnitine acyltransferases in rat tissues. J Biol Chem 1977; 252(22): 7930–1

    PubMed  CAS  Google Scholar 

  9. Pons R, de Vivo DC. Primary and secondary carnitine deficiency syndromes. J Child Neurol 1995; 10 Suppl. 2: S8–24

    PubMed  Google Scholar 

  10. Hoppel C. The role of carnitine in normal and altered fatty acid metabolism. Am J Kidney Dis 2003; 41 (4 Suppl. 4): S4–12

    Article  PubMed  CAS  Google Scholar 

  11. Rebouche CJ, Paulson DJ. Carnitine metabolism and function in humans. Annu Rev Nutr 1986; 6: 41–66

    Article  PubMed  CAS  Google Scholar 

  12. McGarry JD, Brown NF. The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. Eur JBiochem 1997; 244(1): 1–14

    Article  CAS  Google Scholar 

  13. Pande SV, Parvin R. Carnitine-acylcarnitine translocase catalyzes an equilibrating unidirectional transport as well. J Biol Chem 1980; 255(7): 2994–3001

    PubMed  CAS  Google Scholar 

  14. Pande SV. A mitochondrial carnitine acylcarnitine translocase system. Proc Natl Acad Sci U S A 1975; 72(3): 883–7

    Article  PubMed  CAS  Google Scholar 

  15. Miyazawa S, Ozasa H, Osumi T, et al. Purification and properties of carnitine octanoyltransferase and carnitine palmitoyltransferase from rat liver. J Biochem 1983; 94(2): 529–42

    PubMed  CAS  Google Scholar 

  16. Bieber LL. Carnitine. Annu Rev Biochem 1988; 57: 261–83

    Article  PubMed  CAS  Google Scholar 

  17. Ramsay RR, Arduini A. The carnitine acyltransferases and their role in modulating acyl-CoA pools. Arch Biochem Biophys 1993; 302(2): 307–14

    Article  PubMed  CAS  Google Scholar 

  18. Brass EP, Hoppel CL. Relationship between acid-soluble carnitine and coenzyme A pools in vivo. Biochem J 1980; 190(3): 495–504

    PubMed  CAS  Google Scholar 

  19. Osmundsen H, Bremer J, Pedersen JI. Metabolic aspects of peroxisomal beta-oxidation. Biochim Biophys Acta 1991; 1085(2): 141–58

    Article  PubMed  CAS  Google Scholar 

  20. Ramsay RR. The role of the carnitine system in peroxisomal fatty acid oxidation. Am J Med Sci 1999; 318(1): 28–35

    Article  PubMed  CAS  Google Scholar 

  21. Steiber A, Kerner J, Hoppel CL. Carnitine: A nutritional, biosynthetic, and functional perspective. Mol Aspects Med 2004; 25(5–6): 455–73

    Article  PubMed  CAS  Google Scholar 

  22. Rebouche CJ. Metabolic fate of dietary carnitine in humans. In: Carter AL, editor. Current concepts in carnitine research. Boca Raton (FL): CRC Press, 1992: 37–48

    Google Scholar 

  23. Rebouche CJ. Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann N Y Acad Sci 2004; 1033: 30–41

    Article  PubMed  CAS  Google Scholar 

  24. Lombard KA, Olson AL, Nelson SE, et al. Carnitine status of lactoovovegetarians and strict vegetarian adults and children. Am J Clin Nutr 1989; 50(2): 301–6

    PubMed  CAS  Google Scholar 

  25. Li B, Lloyd ML, Gudjonsson H, et al. The effect of enteral carnitine administration in humans. Am J Clin Nutr 1992; 55(4): 838–45

    PubMed  CAS  Google Scholar 

  26. Kato Y, Sugiura M, Sugiura T, et al. Organic cation/carnitine transporter OCTN2 (Slc22a5) is responsible for carnitine transport across apical mem-branes of small intestinal epithelial cells in mouse. Mol Pharmacol 2006; 70(3): 829–37

    Article  PubMed  CAS  Google Scholar 

  27. Gross CJ, Henderson LM. Absorption of D- and L-carnitine by the intestine and kidney tubule in the rat. Biochim Biophys Acta 1984; 772(2): 209–19

    Article  PubMed  CAS  Google Scholar 

  28. Shaw RD, Li BUK, Hamilton JW, et al. Carnitine transport in rat small intestine. Am J Physiol 1983; 245(3): G376–81

    PubMed  CAS  Google Scholar 

  29. McCloud E, Ma TY, Grant KE, et al. Uptake of L-carnitine by a human intestinal epithelial cell line, Caco-2. Gastroenterology 1996; 111(6): 1534–40

    Article  PubMed  CAS  Google Scholar 

  30. Hamilton JW, Li BUK, Shug AL, et al. Carnitine transport in human intestinal biopsy specimens: demonstration of an active transport system. Gastroenterology 1986; 91(1): 10–6

    PubMed  CAS  Google Scholar 

  31. Gudjonsson H, Li BU, Shug AL, et al. In vivo studies of intestinal carnitine absorption in rats. Gastroenterology 1985; 88(6): 1880–7

    PubMed  CAS  Google Scholar 

  32. Gudjonsson H, Li BUK, Shug AL, et al. Studies of carnitine metabolism in relation to intestinal absorption. Am J Physiol 1985; 248(3): G313–9

    PubMed  CAS  Google Scholar 

  33. Gross CJ, Savaiano DA. Effect of development and nutritional state on the uptake, metabolism and release of free and acetyl-L-carnitine by the rodent small intestine. Biochim Biophys Acta 1993; 1170(3): 265–74

    Article  PubMed  CAS  Google Scholar 

  34. Rebouche CJ, Mack DL, Edmonson PF. L-Carnitine dissimilation in the gastrointestinal tract of the rat. Biochemistry 1984; 23(26): 6422–6

    Article  PubMed  CAS  Google Scholar 

  35. Bain MA, Faull R, Milne RW, et al. Oral L-carnitine: metabolite formation and hemodialysis. Curr Drug Metab 2006; 7(7): 811–6

    Article  PubMed  CAS  Google Scholar 

  36. Bain MA, Fornasini G, Evans AM. Trimethylamine: metabolic, pharmacokinetic and safety aspects. Curr Drug Metab 2005; 6(3): 227–40

    Article  PubMed  CAS  Google Scholar 

  37. Rebouche CJ, Chenard CA. Metabolic fate of dietary carnitine in human adults: identification and quantification of urinary and fecal metabolites. J Nutr 1991; 121(4): 539–46

    PubMed  CAS  Google Scholar 

  38. Vaz FM, Wanders RJ. Carnitine biosynthesis in mammals. Biochem J 2002; 361 (Part 3): 417–29

    Article  PubMed  CAS  Google Scholar 

  39. Rebouche CJ. Carnitine function and requirements during the life cycle. FASEB J 1992; 6(15): 3379–86

    PubMed  CAS  Google Scholar 

  40. Tanphaichitr V, Broquist HP. Role of lysine and ε-N-trimethyllysine in carnitine biosynthesis. II: studies in the rat. J Biol Chem 1973; 248(6): 2176–81

    PubMed  CAS  Google Scholar 

  41. Horne DW, Broquist HP. Role of lysine and ε-N-trimethyllysine in carnitine biosynthesis. I: studies in Neurospora crassa. J Biol Chem 1973; 248(6): 2170–5

    PubMed  CAS  Google Scholar 

  42. Hulse JD, Ellis SR, Henderson LM. Carnitine biosynthesis: beta-hydroxylation of trimethyllysine by an alpha-ketoglutarate-dependent mitochondrial dioxygenase. J Biol Chem 1978; 253(5): 1654–9

    PubMed  CAS  Google Scholar 

  43. Sachan DS, Hoppel CL. Carnitine biosynthesis. Hydroxylation of N-6-trimethyl-lysine to 3-hydroxy-N6-trimethyl-lysine. Biochem J 1980; 188(2): 529–34

    PubMed  CAS  Google Scholar 

  44. Sachan DS, Broquist HP. Synthesis of carnitine from epsilon-N-trimethyllysine in post mitochondrial fractions of Neurospora crassa. Biochem Biophys Res Commun 1980; 96(2): 870–5

    Article  PubMed  CAS  Google Scholar 

  45. Rebouche CJ, Bosch EP, Chenard CA, et al. Utilization of dietary precursors for carnitine synthesis in human adults. J Nutr 1989; 119(12): 1907–13

    PubMed  CAS  Google Scholar 

  46. Rebouche CJ, Lehman LJ, Olson L. Epsilon-N-trimethyllysine availability regulates the rate of carnitine biosynthesis in the growing rat. J Nutr 1986; 116(5): 751–9

    PubMed  CAS  Google Scholar 

  47. Rebouche CJ, Engel AG. Tissue distribution of carnitine biosynthetic enzymes in man. Biochim Biophys Acta 1980; 630(1): 22–9

    Article  PubMed  CAS  Google Scholar 

  48. Hulse JD, Henderson LM. Carnitine biosynthesis: purification of 4-N′-tri-methylaminobutyraldehyde dehydrogenase from beef liver. J Biol Chem 1980; 255(3): 1146–51

    PubMed  CAS  Google Scholar 

  49. Englard S, Blanchard JS, Midelfort CF. Gamma-butyrobetaine hydroxylase: stereochemical course of the hydroxylation reaction. Biochemistry 1985; 24(5): 1110–6

    Article  PubMed  CAS  Google Scholar 

  50. Lindstedt G, Lindstedt S. Cofactor requirements of gamma-butyrobetaine hydroxylase from rat liver. J Biol Chem 1970; 245(16): 4178–86

    PubMed  CAS  Google Scholar 

  51. Brass EP. Pharmacokinetic considerations for the therapeutic use of carnitine in hemodialysis patients. Clin Ther 1995; 17(2): 176–85

    Article  PubMed  CAS  Google Scholar 

  52. Reuter SE, Evans AM, Chace DH, et al. Determination of the reference range of endogenous plasma carnitines in healthy adults. Ann Clin Biochem 2008; 45(6): 585–92

    Article  PubMed  CAS  Google Scholar 

  53. Niu YJ, Jiang ZM, Shu H, et al. Assay of carnitine in plasma and urine of healthy adults [in Chinese; abstract]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2002; 24(2): 185–7

    PubMed  CAS  Google Scholar 

  54. Vinci E, Rampello E, Zanoli L, et al. Serum carnitine levels in patients with tumoral cachexia. Eur J Intern Med 2005; 16(6): 419–23

    Article  PubMed  CAS  Google Scholar 

  55. Lohninger A, Sendic A, Staniek H, et al. Endurance exercise training and L-carnitine supplementation stimulates gene expression in the blood and muscle cells in young athletes and middle aged subjects. Monatsh Chem 2005; 136(8): 1425–42

    Article  CAS  Google Scholar 

  56. Bene J, Komlosi K, Gasztonyi B, et al. Plasma carnitine ester profile in adult celiac disease patients maintained on long-term gluten free diet. World J Gastroenterol 2005; 11(42): 6671–5

    PubMed  CAS  Google Scholar 

  57. Jones MG, Goodwin CS, Amjad S, et al. Plasma and urinary carnitine and acylcarnitines in chronic fatigue syndrome. Clin Chim Acta 2005; 360(1–2): 173–7

    Article  PubMed  CAS  Google Scholar 

  58. Wanner C, Wäckerle B, Boeckle H, et al. Plasma and red blood cell carnitine and carnitine esters during L-carnitine therapy in hemodialysis patients. Am J Clin Nutr 1990; 51(3): 407–10

    PubMed  CAS  Google Scholar 

  59. Borum PR. Plasma carnitine compartment and red blood cell carnitine compartment of healthy adults. Am J Clin Nutr 1987; 46(3): 437–41

    PubMed  CAS  Google Scholar 

  60. Furst P, Gloggler A. Reappraisal of carnitine concentrations in blood. Clin Chem 1987; 33(10): 1956–7

    PubMed  CAS  Google Scholar 

  61. Mayer G, Graf H, Legenstein E, et al. L-Carnitine substitution in patients on chronic hemodialysis. Nephron 1989; 52(4): 295–9

    Article  PubMed  CAS  Google Scholar 

  62. Maccari F, Hülsmann WC. (Acyl)carnitine distribution between plasma, erythrocytes, and leukocytes in human blood [letter]. Clin Chem 1989; 35(4): 711

    PubMed  CAS  Google Scholar 

  63. Savica V, Bellinghieri G, di Stefano C, et al. Plasma and muscle carnitine levels in haemodialysis patients with morphological-ultrastructural examination of muscle samples. Nephron 1983; 35(4): 232–6

    Article  PubMed  CAS  Google Scholar 

  64. Leschke M, Rumpf KW, Eisenhauer T, et al. Quantitative assessment of carnitine loss during hemodialysis and hemofiltration. Kidney Int 1983; 24 Suppl. 16: S143–6

    Google Scholar 

  65. Debska-Slizien A, Kawecka A, Wojnarowski K, et al. Correlation between plasma carnitine, muscle carnitine and glycogen levels in maintenance he-modialysis patients. Int J Artif Organs 2000; 23(2): 90–6

    PubMed  CAS  Google Scholar 

  66. Bellinghieri G, Savica V, Mallamace A, et al. Correlation between increased serum and tissue L-carnitine levels and improved muscle symptoms in hemodialyzed patients. Am J Clin Nutr 1983; 38(4): 523–31

    PubMed  CAS  Google Scholar 

  67. Penn D, Schmidt-Sommerfeld E. Carnitine and carnitine esters in plasma and adipose tissue of chronic uremic patients undergoing hemodialysis. Metabolism 1983; 32(8): 806–9

    Article  PubMed  CAS  Google Scholar 

  68. Rodriguez-Segade S, Alonso de la Pena C, Paz JM, et al. Carnitine deficiency in haemodialysed patients. Clin Chim Acta 1986; 159(3): 249–56

    Article  PubMed  CAS  Google Scholar 

  69. Rodriguez-Segade S, Alonso de la Pena C, Paz M, et al. Carnitine concentrations in dialysed and undialysed patients with chronic renal insufficiency. Ann Clin Biochem 1986; 23(6): 671–5

    PubMed  Google Scholar 

  70. Wanner C, Förstner-Wanner S, Schaeffer G, et al. Serum free carnitine, carnitine esters and lipids in patients on peritoneal dialysis and hemodialysis. Am J Nephrol 1986; 6(3): 206–11

    Article  PubMed  CAS  Google Scholar 

  71. Wanner C, Förstner-Wanner S, Rössle C, et al. Carnitine metabolism in patients with chronic renal failure: effect of L-carnitine supplementation. Kidney Int 1987; 32 Suppl. 22: S132–5

    Google Scholar 

  72. Segre G, Bianchi E, Corsi M, et al. Plasma and urine pharmacokinetics of free and of short-chain carnitine after administration of carnitine in man. Arzneimittelforschung 1988; 38(12): 1830–4

    PubMed  CAS  Google Scholar 

  73. Harper P, Wadström C, Cederblad G. Carnitine measurements in liver, muscle tissue, and blood in normal subjects. Clin Chem 1993; 39(4): 592–9

    PubMed  CAS  Google Scholar 

  74. Golper TA, Wolfson M, Ahmad S, et al. Multicenter trial of L-carnitine in maintenance hemodialysis patients. I: carnitine concentrations and lipid effects. Kidney Int 1990; 38(5): 904–11

    Article  PubMed  CAS  Google Scholar 

  75. van Es A, Henny FC, Kooistra MP, et al. Amelioration of cardiac function by L-carnitine administration in patients on haemodialysis. Contrib Nephrol 1992; 98: 28–35

    PubMed  Google Scholar 

  76. Marzo A, Arrigoni-Martelli E, Mancinelli A, et al. Protein binding of L-carnitine family components. Eur J Drug Metab Pharmacokinet 1991; (Spec. No. 3): 364–8

  77. Cooper MB, Forte CA, Jones DA. Carnitine and acetylcarnitine in red blood cells. Biochim Biophys Acta 1988; 959(2): 100–5

    Article  PubMed  CAS  Google Scholar 

  78. Baker H, Frank O, DeAngelis B, et al. Absorption and excretion of L-carnitine during single or multiple dosings in humans. Int J Vitam Nutr Res 1993; 63(1): 22–6

    PubMed  CAS  Google Scholar 

  79. Reuter SE, Faull RJ, Ranieri E, et al. Endogenous plasma carnitine pool composition and response to erythropoietin treatment in chronic haemodialysis patients. Nephrol Dial Transplant 2009; 24(3): 990–6

    Article  PubMed  CAS  Google Scholar 

  80. Arduini A, Tyurin V, Tyuruna Y, et al. Acyl-trafficking in membrane phospholipid fatty acid turnover: the transfer of fatty acid from the acyl-L-carnitine pool to membrane phospholipids in intact human erythrocytes. Biochem Biophys Res Commun 1992; 187(1): 353–8

    Article  PubMed  CAS  Google Scholar 

  81. Lentner C, Diem K, Seldrup J. Geigy scientific tables. 8th rev. and enl. ed. Basel: Ciba-Geigy Ltd, 1981

    Google Scholar 

  82. Rebouche CJ, Engel AG. Carnitine transport in cultured muscle cells and skin fibroblasts from patients with primary systemic carnitine deficiency. In Vitro 1982; 18(5): 495–500

    Article  PubMed  CAS  Google Scholar 

  83. Willner JH, Ginsburg S, Dimauro S. Active transport of carnitine into skeletal muscle. Neurology 1978; 28(7): 721–4

    Article  PubMed  CAS  Google Scholar 

  84. Rebouche CJ. Carnitine movement across muscle cell membranes: studies in isolated rat muscle. Biochim Biophys Acta 1977; 471(1): 145–55

    Article  PubMed  CAS  Google Scholar 

  85. Martinuzzi A, Vergani L, Rosa M, et al. L-Carnitine uptake in differentiating human cultured muscle. Biochim Biophys Acta 1991; 1095(3): 217–22

    Article  PubMed  CAS  Google Scholar 

  86. Angelini C, Vergani L, Martinuzzi A. Clinical and biochemical aspects of carnitine deficiency and insufficiency: transport defects and inborn errors of β-oxidation. Crit Rev Clin Lab Sci 1992; 29(3–4): 217–42

    Article  PubMed  CAS  Google Scholar 

  87. Brooks DE, McIntosh JEA. Turnover of carnitine by rat tissues. Biochem J 1975; 148(3): 439–45

    PubMed  CAS  Google Scholar 

  88. de la Grandmaison GL, Clairand I, Durigon M. Organ weight in 684 adult autopsies: new tables for a Caucasoid population. Forensic Sci Int 2001; 119(2): 149–54

    Article  PubMed  Google Scholar 

  89. Bøhmer T, Eiklid K, Jonsen J. Carnitine uptake into human heart cells in culture. Biochim Biophys Acta 1977; 465(3): 627–33

    Article  PubMed  Google Scholar 

  90. Bahl J, Navin T, Manian AA, et al. Carnitine transport in isolated adult rat heart myocytes and the effect of 7,8-diOH chlorpromazine. Circ Res 1981; 48(3): 378–85

    Article  PubMed  CAS  Google Scholar 

  91. Xuan W, Lamhonwah AM, Librach C, et al. Characterization of organic cation/carnitine transporter family in human sperm. Biochem Biophys Res Commun 2003; 306(1): 121–8

    Article  PubMed  CAS  Google Scholar 

  92. Tamai I, Ohashi R, Nezu JI, et al. Molecular and functional characterization of organic cation/carnitine transporter family in mice. J Biol Chem 2000; 275(51): 40064–72

    Article  PubMed  CAS  Google Scholar 

  93. Tamai I, Ohashi R, Nezu J, et al. Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem 1998; 273(32): 20378–82

    Article  PubMed  CAS  Google Scholar 

  94. Wu X, Huang W, Prasad PD, et al. Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OCTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther 1999; 290(3): 1482–92

    PubMed  CAS  Google Scholar 

  95. Nakanishi T, Hatanaka T, Huang W, et al. Na+− and Clt—coupled active transport of carnitine by the amino acid transporter ATB(0,+) from mouse colon expressed in HRPE cells and Xenopus oocytes. J Physiol 2001; 532 (Pt 2): 297–304

    Article  PubMed  CAS  Google Scholar 

  96. Taylor PM. Absorbing competition for carnitine. J Physiol 2001; 532 (Pt 2): 283

    Article  PubMed  CAS  Google Scholar 

  97. Tsuchida H, Anzai N, Shin HJ, et al. Identification of a novel organic anion transporter mediating carnitine transport in mouse liver and kidney. Cell Physiol Biochem 2010; 25(4–5): 511–22

    Article  PubMed  CAS  Google Scholar 

  98. Ahmad S. Carnitine, kidney and renal dialysis. In: Ferrari R, DiMauro S, Sherwood G, editors. L-Carnitine and its role in medicine: from function to therapy. New York: Academic Press, 1992: 381–400

    Google Scholar 

  99. Guder WG, Wagner S. The role of the kidney in carnitine metabolism. J Clin Chem Clin Biochem 1990; 28(5): 347–50

    PubMed  CAS  Google Scholar 

  100. Hokland BM, Bremer J. Metabolism and excretion of carnitine and acylcarnitines in the perfused rat kidney. Biochim Biophys Acta 1986; 886(2): 223–30

    Article  PubMed  CAS  Google Scholar 

  101. Suzuki Y, Masumura Y, Kobayashi A, et al. Myocardial carnitine deficiency in chronic heart failure [letter]. Lancet 1982; 1(8263): 116

    Article  PubMed  CAS  Google Scholar 

  102. Rebouche CJ, Lombard KA, Chenard CA. Renal adaptation to dietary carnitine in humans. Am J Clin Nutr 1993; 58(5): 660–5

    PubMed  CAS  Google Scholar 

  103. Rebouche CJ, Mack DL. Sodium gradient-stimulated transport of L-carnitine into renal brush border membrane vesicles: kinetics, specificity, and regulation by dietary carnitine. Arch Biochem Biophys 1984; 235(2): 393–402

    Article  PubMed  CAS  Google Scholar 

  104. Rebouche CJ. Quantitative estimation of absorption and degradation of a carnitine supplement by human adults. Metabolism 1991; 40(12): 1305–10

    Article  PubMed  CAS  Google Scholar 

  105. Harper P, Elwin CE, Cederblad G. Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects. Eur J Clin Pharmacol 1988; 35(1): 69–75

    Article  PubMed  CAS  Google Scholar 

  106. Huth PJ, Shug AL. Properties of carnitine transport in rat kidney cortex slices. Biochim Biophys Acta 1980; 602(3): 621–34

    Article  PubMed  CAS  Google Scholar 

  107. Brady PS, Ramsey RR, Brady LJ. Regulation of the long-chain carnitine acyltransferases. FASEB J 1993; 7(11): 1039–44

    PubMed  CAS  Google Scholar 

  108. Calvani M, Reda E, Arrigoni-Martelli E. Regulation by carnitine of myocardial fatty acid and carbohydrate metabolism under normal and patho-logical conditions. Basic Res Cardiol 2000; 95(2): 75–83

    Article  PubMed  CAS  Google Scholar 

  109. Chien D, Dean D, Saha AK, et al. Malonyl-CoA content and fatty acid oxidation in rat muscle and liver in vivo. Am J Physiol Endocrinol Metab 2000; 279(242–2): E259–65

    PubMed  CAS  Google Scholar 

  110. McGarry JD, Stark MJ, Foster DW. Hepatic malonyl-CoA levels of fed, fasted and diabetic rats as measured using a simple radioisotopic assay. J Biol Chem 1978; 253(22): 8291–3

    PubMed  CAS  Google Scholar 

  111. Peluso G, Petillo O, Margarucci S, et al. Differential carnitine/acylcarnitine translocase expression defines distinct metabolic signatures in skeletal muscle cells. J Cell Physiol 2005; 203(2): 439–46

    Article  PubMed  CAS  Google Scholar 

  112. Mancinelli A, Longo A, Shanahan K, et al. Disposition of L-carnitine and acetyl-L-carnitine in the isolated perfused rat kidney. J Pharmacol Exp Ther 1995; 274(3): 1122–8

    PubMed  CAS  Google Scholar 

  113. de Sousa C, English NR, Stacey TE, et al. Measurement of L-carnitine and acylcarnitines in body fluids and tissues in children and in adults. Clin Chim Acta 1990; 187(3): 317–28

    Article  PubMed  Google Scholar 

  114. Bøhmer T, Rydning A, Solberg HE. Carnitine levels in human serum in health and disease. Clin Chim Acta 1974; 57(1): 55–61

    Article  PubMed  Google Scholar 

  115. Cederblad G, Lindstedt S. A method for the determination of carnitine in the picomole range. Clin Chim Acta 1972; 37: 235–43

    Article  PubMed  CAS  Google Scholar 

  116. McGarry JD, Foster DW. An improved and simplified radio-isotopic assay for the determination of free and esterified carnitine. J Lipid Res 1976; 17(3): 277–81

    PubMed  CAS  Google Scholar 

  117. Parvin R, Pande S. Microdetermination of (−)carnitine and carnitine acetyl-transferase activity. Anal Biochem 1977; 79(1–2): 190–201

    Article  PubMed  CAS  Google Scholar 

  118. Pande SV, Caramancion MN. A simple radioisotopic assay of acetylcarnitine and acetyl-CoA at picomolar levels. Anal Biochem 1981; 112(1): 30–8

    Article  PubMed  CAS  Google Scholar 

  119. Pande SV. Radioisotopic assay of acetylcarnitine and acetyl-CoA. Methods Enzymol 1986; 123: 259–63

    Article  PubMed  CAS  Google Scholar 

  120. Bieber LL, Kerner J. Short-chain acylcarnitines: identification and quantitation. Methods Enzymol 1986; 123: 264–76

    Article  PubMed  CAS  Google Scholar 

  121. Kerner J, Bieber LL. A radioisotopic-exchange method for quantification of short-chain (acid-soluble) acylcarnitines. Anal Biochem 1983; 134(2): 459–66

    Article  PubMed  CAS  Google Scholar 

  122. Schmidt-Sommerfeld E, Penn D, Duran M, et al. Detection of inborn errors of fatty acid oxidation from acylcarnitine analysis of plasma and blood spots with the radioisotopic exchange-high-performance liquid chromatographic method. J Pediatr 1993; 122 (5 I): 708–14

    Article  PubMed  CAS  Google Scholar 

  123. Schmidt-Sommerfeld E, Zhang L, Bobrowski PJ, et al. Quantitation of short-and medium-chain acylcarnitines in plasma by radioisotopic exchange/high-performance liquid chromatography. Anal Biochem 1995; 231(1): 27–33

    Article  PubMed  CAS  Google Scholar 

  124. Minkler PE, Hoppel CL. Quantification of free carnitine, individual short-and medium-chain acylcarnitines, and total carnitine in plasma by high-performance liquid chromatography. Anal Biochem 1993; 212(2): 510–8

    Article  PubMed  CAS  Google Scholar 

  125. Chace DH, di Perna JC, Mitchell BL, et al. Electrospray tandem mass spectrometry for analysis of acylcarnitines in dried post-mortem blood specimens collected at autopsy from infants with unexplained cause of death. Clin Chem 2001; 47(7): 1166–82

    PubMed  CAS  Google Scholar 

  126. Naylor EW, Chace DH. Automated tandem mass spectrometry for mass newborn screening for disorders in fatty acid, organic acid, and amino acid metabolism. J Child Neurol 1999; 14 Suppl. 1: S4–8

    PubMed  Google Scholar 

  127. Wiley V, Carpenter K, Wilcken B. Newborn screening with tandem mass spectrometry: 12 months’ experience in NSW Australia. Acta Paediatr Suppl 1999; 88(432): 48–51

    Article  PubMed  CAS  Google Scholar 

  128. Reuter SE, Evans AM, Faull RJ, et al. Impact of haemodialysis on individual endogenous plasma acylcarnitine concentrations in end-stage renal disease. Ann Clin Biochem 2005; 42(5): 387–93

    Article  PubMed  CAS  Google Scholar 

  129. Minkler PE, Brass EP, Hiatt WR, et al. Quantification of carnitine, acetylcarnitine, and total carnitine in tissues by high-performance liquid chro-matography: the effect of exercise on carnitine homeostasis in man. Anal Biochem 1995; 231(2): 315–22

    Article  PubMed  CAS  Google Scholar 

  130. Angsten G, Cederblad G, Meurling S. Reference ranges for muscle carnitine concentration in children. Ann Clin Biochem 2003; 40 (Pt 4): 406–10

    Article  PubMed  CAS  Google Scholar 

  131. Marquis NR, Fritz IB. The distribution of carnitine, acetylcarnitine, and carnitine acetyltransferase in rat tissues. J Biol Chem 1965; 240: 2193–6

    PubMed  CAS  Google Scholar 

  132. Rebouche CJ, Engel AG. Kinetic compartmental analysis of carnitine metabolism in the dog. Arch Biochem Biophys 1983; 220(1): 60–70

    Article  PubMed  CAS  Google Scholar 

  133. Lai HS, Chen Y, Chen WJ. Carnitine contents in remnant liver, kidney, and skeletal muscle after partial hepatectomy in rats: randomized trial. World J Surg 1998; 22(1): 42–7

    Article  PubMed  CAS  Google Scholar 

  134. Violante S, Ijlst L, van Lenthe H, et al. Carnitine palmitoyltransferase 2: new insights on the substrate specificity and implications for acylcarnitine profiling. Biochem Biophys Acta 2010; 1802(9): 728–32

    Article  PubMed  CAS  Google Scholar 

  135. Bøhmer T, Norum KR, Bremer J. The relative amounts of long-chain acylcarnitine, acetylcarnitine, and free carnitine in organs of rats in different nutritional states and with alloxan diabetes. Biochim Biophys Acta 1966; 125(2): 244–51

    Article  Google Scholar 

  136. Faergeman NJ, Knudsen J. Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signalling. Biochem J 1997; 323(1): 1–12

    PubMed  CAS  Google Scholar 

  137. Sim KG, Hammond J, Wilcken B. Strategies for the diagnosis of mitochondrial fatty acid beta-oxidation disorders. Clin Chim Acta 2002; 323(1–2): 37–58

    Article  PubMed  CAS  Google Scholar 

  138. Ventura FV, Costa CG, Struys EA, et al. Quantitative acylcarnitine profiling in fibroblasts using [U-13C] palmitic acid: An improved tool for the diag-nosis of fatty acid oxidation defects. Clin Chim Acta 1999; 281(1–2): 1–17

    Article  PubMed  CAS  Google Scholar 

  139. Duran M, Mitchell G, de Klerk JBC. Octanoic academia and octanoylcarnitine excretion with dicarboxylic aciduria due to defective oxidation of medium-chain fatty acids. J Pediatr 1985; 107(3): 397–404

    Article  PubMed  CAS  Google Scholar 

  140. Millington DS, Roe CR, Maltby DA. Characterization of new diagnostic acylcarnitines in patients with β-ketothiolase deficiency and glutaric aciduria type I using mass spectrometry. Biomed Environm Mass Spectrom 1987; 14(12): 711–6

    Article  CAS  Google Scholar 

  141. Morrow RJ, Rose ME. Isolation of acylcarnitines from urine: a comparison of methods and application to long-chain acyl-CoA dehydrogenase deficiency. Clin Chim Acta 1992; 211(1–2): 73–81

    Article  PubMed  CAS  Google Scholar 

  142. Brown NF, Mullur RS, Subramanian I, et al. Molecular characterization of L-CPT I deficiency in six patients: Insights into function of the native enzyme. J Lipid Res 2001; 42(7): 1134–42

    PubMed  CAS  Google Scholar 

  143. Lionetti V, Stanley WC, Recchia FA. Modulating fatty acid oxidation in heart failure. Cardiovasc Res 2011; 90(2): 202–9

    Article  PubMed  CAS  Google Scholar 

  144. Marquis NR, Francesconi RP, Villee CA. A role for carnitine and long chain acylcarnitine in the regulation of lipogenesis. Adv Enzyme Regul 1968; 6(C): 31–55

    Article  PubMed  CAS  Google Scholar 

  145. Martin DB, Vagelos PR. The mechanism of tricarboxylic acid cycle regulation of fatty acid synthesis. J Biol Chem 1962; 237(6): 1787–92

    PubMed  CAS  Google Scholar 

  146. Numa S, Bortz WM, Lynen F. Regulation of fatty acid synthesis at the acetyl-CoA carboxylation step. Adv Enzyme Regul 1965; 3(C): 407–23

    Article  CAS  Google Scholar 

  147. Trumble GE, Smith MA, Winder WW. Purification and characterization of rat skeletal muscle acetyl-CoA carboxylase. Eur J Biochem 1995; 231(1): 192–8

    Article  PubMed  CAS  Google Scholar 

  148. Vagelos PR, Alberts AW, Martin DB. Studies on the mechanism of activation of acetyl coenzyme A carboxylase by citrate. J Biol Chem 1963; 238(2): 533–40

    PubMed  CAS  Google Scholar 

  149. Scholte HR, Luyt-Houwen IE, Vaandrager-Verduin MH. The role of the carnitine system in myocardial fatty acid oxidation: carnitine deficiency, failing mitochondria and cardiomyopathy. Basic Res Cardiol 1987; 82 Suppl. 1: 63–73

    PubMed  CAS  Google Scholar 

  150. Fritz IB, Hsu MP. Studies on the control of fatty acid synthesis. 1: stimulation by (+) palmitylcarnitine of fatty acid synthesis in liver preparations from fed and fasted rats. J Biol Chem 1967; 242(5): 865–72

    PubMed  CAS  Google Scholar 

  151. Fritz IB, Arrigoni-Martelli E. Sites of action of carnitine and its derivatives on the cardiovascular system: interactions with membranes. Trends Pharmacol Sci 1993; 14(10): 355–60

    Article  PubMed  CAS  Google Scholar 

  152. Scholte HR, Jennekens FGI, Bouvy JJBJ. Carnitine palmitoyltransferase II deficiency with normal carnitine palmitoyltransferase I in skeletal muscle and leukocytes. J Neurol Sci 1979; 40(1): 39–51

    Article  PubMed  CAS  Google Scholar 

  153. Scholte HR, Hülsmann WC, Luyt-Houwen IEM, et al. Carnitine palmitoyltransferase deficiencies. Biochem Soc Trans 1985; 13(4): 643–5

    PubMed  CAS  Google Scholar 

  154. Echabe T, Requero MA, Goñi FM, et al. An infrared investigation of palmitoyl-coenzyme A and palmitoylcarnitine interaction with perdeuterated-chain phospholipid bilayers. Eur J Biochem 1995; 231(1): 199–203

    Article  PubMed  CAS  Google Scholar 

  155. Fritz IB, Marquis NR. The role of acylcarnitine esters and carnitine palmityltransferase in the transport of fatty acyl groups across mitochondrial membranes. Proc Natl Acad Sci U S A 1965; 54(4): 1226–33

    Article  PubMed  CAS  Google Scholar 

  156. Goñi FM, Requero MA, Alonso A. Palmitoylcarnitine, a surface-active metabolite. FEBS Lett 1996; 390(1): 1–5

    Article  PubMed  Google Scholar 

  157. Requero MA, Goñi FM, Alonso A. The membrane-perturbing properties of palmitoyl-coenzyme A and palmitoylcarnitine: a comparative study. Bio-chemistry 1995; 34(3): 10400–5

    CAS  Google Scholar 

  158. Requero MA, Gonzales M, Goñi FM, et al. Differential penetration of fatty acyl-coenzyme A and fatty acylcarnitines into phospholipid monolayers. FEBS Lett 1995; 357(1): 75–8

    Article  PubMed  CAS  Google Scholar 

  159. Yamada KA, Kanter EM, Newatia A. Long-chain acylcarnitine induces Ca2+ efflux from the sarcoplasmic reticulum. J Cardiovasc Pharmacol 2000; 36(1): 14–21

    Article  PubMed  CAS  Google Scholar 

  160. Kobayashi A, Watanabe H, Fujisawa S, et al. Effects of L-carnitine and palmitoylcarnitine on membrane fluidity of human erythrocytes. Biochim Biophys Acta 1989; 986(1): 83–8

    Article  PubMed  CAS  Google Scholar 

  161. Cho KS, Proulx P. Lysis of erythrocytes by long-chain acyl esters of carnitine. Biochim Biophys Acta 1969; 193(1): 30–5

    Article  PubMed  CAS  Google Scholar 

  162. Cho KS, Proulx P. Studies on the mechanism of hemolysis by acyl carnitines, lysolecithins and acyl cholines. Biochim Biophys Acta 1971; 225(2): 214–23

    Article  PubMed  CAS  Google Scholar 

  163. Cho KS, Proulx P. Interactions of acyl carnitines and other lysins with erythrocytes and reconstituted erythrocyte lipoproteins. Biochim Biophys Acta 1973; 318(1): 50–60

    Article  PubMed  CAS  Google Scholar 

  164. Newgard CB, An J, Bain JR, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and con-tributes to insulin resistance. Cell Metab 2009; 9(4): 311–26

    Article  PubMed  CAS  Google Scholar 

  165. Adams SH, Hoppel CL, Lok KH, et al. Plasma acylcarnitine profiles suggest incomplete long-chain fatty acid β-oxidation and altered tricarboxylic acid cycle activity in type 2 diabetic African-American women. J Nutr 2009; 139(6): 1073–81

    Article  PubMed  CAS  Google Scholar 

  166. Huffman KM, Shah SH, Stevens RD, et al. Relationships between circulating metabolic intermediates and insulin action in overweight to obese, inactive men and women. Diabetes Care 2009; 32(9): 1678–83

    Article  PubMed  CAS  Google Scholar 

  167. Koves TR, Ussher JR, Noland RC, et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab 2008; 7(1): 45–56

    Article  PubMed  CAS  Google Scholar 

  168. Muoio DM, Newgard CB. Obesity-related derangements in metabolic regulation. Annu Rev Biochem 2006; 75: 367–401

    Article  PubMed  CAS  Google Scholar 

  169. Muoio DM, Newgard CB. Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes. Nat Rev Mol Cell Biol 2008; 9(3): 193–205

    Article  PubMed  CAS  Google Scholar 

  170. Noland RC, Koves TR, Seiler SE, et al. Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control. J Biol Chem 2009; 284(34): 22840–52

    Article  PubMed  CAS  Google Scholar 

  171. Shah SH, Hauser ER, Bain JR, et al. High heritability of metabolomic profiles in families burdened with premature cardiovascular disease. Mol Syst Biol 2009; 5(258): 1–7

    Google Scholar 

  172. Tai ES, Tan ML, Stevens RD, et al. Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men. Diabetologia 2010; 53: 757–67

    Article  PubMed  CAS  Google Scholar 

  173. Redman LM, Huffman KM, Landerman LR, et al. Effect of caloric restriction with and without exercise on metabolic intermediates in nonobese men and women. J Clin Endocrinol Metab 2011; 96(2): E312–21

    Article  PubMed  CAS  Google Scholar 

  174. Lum H, Sloane R, Huffman KM, et al. Plasma acylcarnitines are associated with physical performance in elderly men. J Gerontol A Biol Sci Med Sci 2011; 66A(5): 548–53

    Article  CAS  Google Scholar 

  175. Ferrari R, Merli E, Cicchitelli G, et al. Therapeutic effects of L-carnitine and propionyl-L-carnitine on cardiovascular diseases: a review. Ann N Y Acad Sci 2004; 1033:79–91

    Article  PubMed  CAS  Google Scholar 

  176. Palacios HH, Yendluri BB, Parvathaneni K, et al. Mitochondrion-specific antioxidants as drug treatments for Alzheimer disease. CNS Neurol Disord Drug Targets 2011; 10(2): 149–62

    Article  PubMed  CAS  Google Scholar 

  177. Rosca MG, Lemieux H, Hoppel CL. Mitochondria in the elderly: Is acetylcarnitine a rejuvenator? Adv Drug Deliv Rev 2009; 61(14): 1332–42

    Article  PubMed  CAS  Google Scholar 

  178. Goa KL, Brogden RN. L-Carnitine: a preliminary review of its pharmacokinetics, and its therapeutic use in ischaemic cardiac disease and primary and secondary carnitine deficiencies in relationship to its role in fatty acid metabolism. Drugs 1987; 34(1): 1–24

    Article  PubMed  CAS  Google Scholar 

  179. Famularo G, Matricardi F, Nucera E, et al. Carnitine deficiency: primary and secondary syndromes. In: de Simone C, Famularo G, editors. Carnitine today. Austin (TX): RG Landes Company, 1997: 119–61

    Chapter  Google Scholar 

  180. Rebouche CJ, Engel AG. Carnitine metabolism and deficiency syndromes. Mayo Clin Proc 1983; 58(8): 533–40

    PubMed  CAS  Google Scholar 

  181. Rodrigues Pereira R, Scholte HR, Luyt-Houwen IE, et al. Cardiomyopathy associated with carnitine loss in kidneys and small intestine. Eur J Pediatr 1988; 148: 193–7

    Article  Google Scholar 

  182. Vaz FM, Scholte HR, Ruiter J, et al. Identification of two novel mutations in OCTN2 of three patients with systemic carnitine deficiency. Hum Genet 1999; 105(1–2): 157–61

    Article  PubMed  CAS  Google Scholar 

  183. Treem WR, Stanley CA, Finegold DN, et al. Primary carnitine deficiency due to a failure of carnitine transport in kidney, muscle, and fibroblasts. N Engl J Med 1988; 319(20): 1331–6

    Article  PubMed  CAS  Google Scholar 

  184. Tang NL, Ganapathy V, Wu X, et al. Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency. Hum Mol Genet 1999; 8(4): 655–60

    Article  PubMed  CAS  Google Scholar 

  185. Nezu J, Tamai I, Oku A, et al. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet 1999; 21(1): 91–4

    Article  PubMed  CAS  Google Scholar 

  186. Wang Y, Ye J, Ganapathy V, et al. Mutations in the organic cation/carnitine transporter OCTN2 in primary carnitine deficiency. Proc Natl Acad Sci U S A 1999; 96(5): 2356–60

    Article  PubMed  CAS  Google Scholar 

  187. Stanley CA, DeLeeuw S, Coates PM, et al. Chronic cardiomyopathy and weakness or acute coma in children with a defect in carnitine uptake. Ann Neurol 1991; 30(5): 709–16

    Article  PubMed  CAS  Google Scholar 

  188. Waber LJ, Valle D, Neill C, et al. Carnitine deficiency presenting as familial cardiomyopathy: a treatable defect in carnitine transport. J Pediatr 1982; 101(5): 700–5

    Article  PubMed  CAS  Google Scholar 

  189. Shapira Y, Glick B, Harel S, et al. Infantile idiopathic myopathic carnitine deficiency: treatment with L-carnitine. Pediatr Neurol 1993; 9(1): 35–8

    Article  PubMed  CAS  Google Scholar 

  190. Tanphaichitr V, Leelahagul P. Carnitine metabolism and human carnitine deficiency. Nutrition 1993; 9(3): 246–54

    PubMed  CAS  Google Scholar 

  191. Turnbull DM, Bartlett K, Stevens DL, et al. Short-chain acyl-CoA dehydrogenase deficiency associated with a lipid-storage myopathy and secondary carnitine deficiency. N Engl J Med 1984; 311(19): 1232–6

    Article  PubMed  CAS  Google Scholar 

  192. Guarnieri G, Toigo G, Crapesi L, et al. Carnitine metabolism in chronic renal failure. Kidney Int 1987; 22 Suppl. 22: S116–27

    CAS  Google Scholar 

  193. Evans AM. Dialysis-related carnitine disorder and levocarnitine pharmacology. Am J Kidney Dis 2003; 41 (4 Suppl. 4): S13–26

    Article  PubMed  CAS  Google Scholar 

  194. Rudman D, Sewell CW, Ansley JD. Deficiency of carnitine in cachectic cirrhotic patients. J Clin Invest 1977; 60(3): 716–23

    Article  PubMed  CAS  Google Scholar 

  195. Krahenbuhl S. Carnitine metabolism in chronic liver disease. Life Sci 1996; 59(19): 1579–99

    Article  PubMed  CAS  Google Scholar 

  196. Khan L, Bamji MS. Plasma carnitine levels in children with protein-calorie malnutrition before and after rehabilitation. Clin Chim Acta 1977; 75(1): 163–6

    Article  PubMed  CAS  Google Scholar 

  197. de Simone C, Tzantzoglou S, Jirillo E, et al. L-Carnitine deficiency in AIDS patients. AIDS 1992; 6(2): 203–5

    Article  PubMed  Google Scholar 

  198. Scholte HR, Stinis JT, Jennekens FG. Low carnitine levels in serum of pregnant women. N Engl J Med 1978; 299(19): 1079–80

    PubMed  CAS  Google Scholar 

  199. Bernardini I, Rizzo WB, Dalakas M, et al. Plasma and muscle free carnitine deficiency due to renal Fanconi syndrome. J Clin Invest 1985; 75(4): 1124–30

    Article  PubMed  CAS  Google Scholar 

  200. Filipek PA, Juranek J, Nguyen MT, et al. Relative carnitine deficiency in autism. J Autism Dev Disord 2004; 34(6): 615–23

    Article  PubMed  Google Scholar 

  201. Pepine CJ. The therapeutic potential of carnitine in cardiovascular disorders. Clin Ther 1991; 13(1): 2–21

    PubMed  CAS  Google Scholar 

  202. Kelly GS. L-Carnitine: therapeutic applications of a conditionally-essential amino acid. Altern Med Rev 1998; 3(5): 345–60

    PubMed  CAS  Google Scholar 

  203. Reuter SE, Evans AM. Long-chain acylcarnitine deficiency in patients with chronic fatigue syndrome: potential involvement of altered carnitine palmitoyltransferase-I activity. J Intern Med 2011; 270(1): 76–84

    Article  PubMed  CAS  Google Scholar 

  204. Passeri M, Iannuccelli M, Ciotti G, et al. Mental impairment in aging: selection of patients, methods of evaluation and therapeutic possibilities of acetyl-L-carnitine. Int J Clin Pharmacol Res 1988; 8(5): 367–76

    PubMed  CAS  Google Scholar 

  205. Passeri M, Cucinotta D, Bonati PA, et al. Acetyl-L-carnitine in the treatment of mildly demented elderly patients. Int J Clin Pharmacol Res 1990; 10(1–2): 75–9

    PubMed  CAS  Google Scholar 

  206. Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer’s disease. Int Clin Psychopharmacol 2003; 18(2): 61–71

    Article  PubMed  Google Scholar 

  207. Wiseman LR, Brogden RN. Propionyl-L-carnitine. Drugs Aging 1998; 12(3): 243–50

    Article  PubMed  CAS  Google Scholar 

  208. Brevetti G, Perna S, Sabba C, et al. Effect of propionyl-L-carnitine on quality of life in intermittent claudication. Am J Cardiol 1997; 79(6): 777–80

    Article  PubMed  CAS  Google Scholar 

  209. Rossini M, di Munno O, Valentini G, et al. Double-blind, multicenter trial comparing acetyl L-carnitine with placebo in the treatment of fibromyalgia patients. Clin Exp Rheumatol 2007; 25(2): 182–8

    PubMed  CAS  Google Scholar 

  210. Vermeulen RCW, Scholte HR. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Psychosom Med 2004; 66(2): 276–82

    Article  PubMed  CAS  Google Scholar 

  211. Ahluwalia NS, Bernad NG. A review of valproic acid-induced carnitine deficiency and replacement. J Pharm Technol 2001; 17(3): 81–3

    CAS  Google Scholar 

  212. Ohashi R, Tamai I, Yabuuchi H, et al. Na+-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther 1999; 291(2): 778–84

    PubMed  CAS  Google Scholar 

  213. Murakami K, Sugimoto T, Woo M, et al. Effect of L-carnitine supplementation on acute valproate intoxication. Epilepsia 1996; 37(7): 687–9

    Article  PubMed  CAS  Google Scholar 

  214. Wanner C, Hörl WH. Carnitine abnormalities in patients with renal insufficiency: pathophysiological and therapeutical aspects. Nephron 1988; 50(2): 89–102

    Article  PubMed  CAS  Google Scholar 

  215. Bartel LL, Hussey JL, Shrago E. Perturbation of serum carnitine levels in human adults by chronic renal disease and dialysis therapy. Am J Clin Nutr 1981; 34(7): 1314–20

    PubMed  CAS  Google Scholar 

  216. Evans AM, Fornasini G. Pharmacokinetics of L-carnitine. Clin Pharmacokinet 2003; 42(11): 941–67

    Article  PubMed  CAS  Google Scholar 

  217. Bøhmer T, Bergrem H, Eiklid K. Carnitine deficiency induced during intermittent haemodialysis for renal failure. Lancet 1978; 1(8056): 126–8

    Article  PubMed  Google Scholar 

  218. Evans AM, Faull R, Fornasini G, et al. Pharmacokinetics of L-carnitine in patients with end-stage renal disease undergoing long-term hemodialysis. Clin Pharmacol Ther 2000; 68(3): 238–49

    Article  PubMed  CAS  Google Scholar 

  219. Evans AM, Faull RJ, Nation RL, et al. Impact of hemodialysis on endogenous plasma and muscle carnitine levels in patients with end-stage renal disease. Kidney Int 2004; 66(4): 1527–34

    Article  PubMed  CAS  Google Scholar 

  220. Sahajwalla CG, Helton ED, Purich ED, et al. Multiple-dose pharmacokinetics and bioequivalence of L-carnitine 330-mg tablet versus 1-g chewable tablet versus enteral solution in healthy adult male volunteers. J Pharm Sci 1995; 84(5): 627–33

    Article  PubMed  CAS  Google Scholar 

  221. Rizza V, Lorefice R, Rizza N, et al. Pharmacokinetics of L-carnitine in human subjects. In: Ferrari R, DiMauro S, Sherwood G, editors. L-Carnitine and its role in medicine: From function to therapy. London: Academic Press Limited, 1992: 63–77

    Google Scholar 

  222. Cao Y, Wang YX, Liu CJ, et al. Comparison of pharmacokinetics of L-carnitine, acetyl-L-carnitine and propionyl-L-carnitine after single oral administration of L-carnitine in healthy volunteers. Clin Invest Med 2009; 32(1): E13–9

    PubMed  CAS  Google Scholar 

  223. Bain MA, Milne RW, Evans AM. Disposition and metabolite kinetics of oral L-carnitine in humans. J Clin Pharmacol 2006; 46(10): 1163–70

    Article  PubMed  CAS  Google Scholar 

  224. Bach AC, Schirardin H, Sihr MO, et al. Free and total carnitine in human serum after oral ingestion of L-carnitine. Diabete Metab 1983; 9(2): 121–4

    PubMed  CAS  Google Scholar 

  225. Pace S, Longo A, Toon S, et al. Pharmacokinetics of propionyl-L-carnitine in humans: evidence for saturable tubular reabsorption. Br J Clin Pharmacol 2000; 50(5): 441–8

    Article  PubMed  CAS  Google Scholar 

  226. Kwon OS, Chung YB. HPLC determination and pharmacokinetics of endogenous acetyl-L-carnitine (ALC) in human volunteers orally administered a single dose of ALC. Arch Pharm Res 2004; 27(6): 676–81

    Article  PubMed  CAS  Google Scholar 

  227. Mancinelli A, Longo A, Nation RL, et al. Disposition of L-carnitine and its short-chain esters, acetyl-L-carnitine and propionyl-L-carnitine, in the rat isolated perfused liver. Drug Metab Dispos 2000; 28(12): 1401–4

    PubMed  CAS  Google Scholar 

  228. Sahajwalla CG, Helton ED, Purich ED, et al. Comparison of L-carnitine pharmacokinetics with and without baseline correction following administration of single 20-mg/kg intravenous dose. J Pharm Sci 1995; 84(5): 634–9

    Article  PubMed  CAS  Google Scholar 

  229. Uematsu T, Itaya T, Nishimoto M, et al. Pharmacokinetics and safety of L-carnitine infused i.v. in healthy subjects. Eur J Clin Pharmacol 1988; 34(2): 213–6

    Article  PubMed  CAS  Google Scholar 

  230. Rebouche CJ, Engel AG. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes: evidence for alterations in tissue carnitine transport. J Clin Invest 1984; 73(3): 857–67

    Article  PubMed  CAS  Google Scholar 

  231. Gloggler A, Bulla M, Furst P. Kinetics of intravenously administered carnitine in haemodialysed children. J Pharm Biomed Anal 1990; 8(5): 411–4

    Article  PubMed  CAS  Google Scholar 

  232. Vernez L, Dickenmann M, Steiger J, et al. Effect of L-carnitine on the kinetics of carnitine, acylcarnitines and butyrobetaine in long-term haemodialysis. Nephrol Dial Transplant 2006; 21(2): 450–8

    Article  PubMed  CAS  Google Scholar 

  233. Fornasini G, Upton RN, Evans AM. A pharmacokinetic model for L-carnitine in patients receiving haemodialysis. Br J Clin Pharmacol 2007; 64(3): 335–45

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by an unrestricted project grant from the National Health and Medical Research Council of Australia. The authors declare that no conflict of interest exists.

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  1. School of Pharmacy & Medical Sciences, University of South Australia, GPO Box 2471, Adelaide, South Australia, 5001, Australia

    Stephanie E. Reuter & Allan M. Evans

  2. Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia

    Stephanie E. Reuter & Allan M. Evans

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Reuter, S.E., Evans, A.M. Carnitine and Acylcarnitines. Clin Pharmacokinet 51, 553–572 (2012). https://doi.org/10.1007/BF03261931

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