Acetylcarnitine

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Acetylcarnitine
(R)-Acetylcarnitine V.3.svg
Systematic (IUPAC) name
(R)-3-acetyloxy-4-trimethylammonio-butanoate
Clinical data
AHFS/Drugs.comInternational Drug Names
Legal statusOver-the-counter
RoutesOral
Pharmacokinetic data
Half-life4.2 hours[1]
Identifiers
CAS number3040-38-8 YesY
ATC codeN06BX12
PubChemCID 7045767
ChemSpider5406074 YesY
UNII6DH1W9VH8Q YesY
ChEBICHEBI:57589 YesY
ChEMBLCHEMBL1697733 N
Chemical data
FormulaC9H17NO4 
Mol. mass203.236
 N (what is this?)  (verify)
 
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Acetylcarnitine
(R)-Acetylcarnitine V.3.svg
Systematic (IUPAC) name
(R)-3-acetyloxy-4-trimethylammonio-butanoate
Clinical data
AHFS/Drugs.comInternational Drug Names
Legal statusOver-the-counter
RoutesOral
Pharmacokinetic data
Half-life4.2 hours[1]
Identifiers
CAS number3040-38-8 YesY
ATC codeN06BX12
PubChemCID 7045767
ChemSpider5406074 YesY
UNII6DH1W9VH8Q YesY
ChEBICHEBI:57589 YesY
ChEMBLCHEMBL1697733 N
Chemical data
FormulaC9H17NO4 
Mol. mass203.236
 N (what is this?)  (verify)

Acetyl-L-carnitine or ALCAR, is an acetylated form of L-carnitine. It is naturally produced by the body, although it is often taken as a dietary supplement. Acetylcarnitine is broken down in the blood by plasma esterases to carnitine which is used by the body to transport fatty acids into the mitochondria for breakdown.[2]

Biochemical production and action[edit]

ALCAR is an acetylated derivative of L-carnitine. During strenuous exercise, a large portion of L-carnitine and unused acetyl-CoA are converted to ALCAR and CoA inside mitochondria by carnitine O-acetyltransferase.[2][3] The ALCAR is transported outside the mitochondria where it converts back to the two constituents. The L-carnitine is cycled back into the mitochondria with acyl groups to facilitate fatty acid utilization, but excess acetyl-CoA may block it.[4][5] Excess acetyl-CoA causes more carbohydrates to be used for energy at the expense of fatty acids. This occurs by different mechanisms inside and outside the mitochondria. ALCAR transport decreases acetyl-CoA inside the mitochondria, but increases it outside.[6][7] Glucose metabolism in diabetics improves with administration of either ALCAR[8] or L-carnitine.[9] ALCAR decreases glucose consumption in favor of fat oxidation in non-diabetics.[10] A portion of L-carnitine is converted to ALCAR after ingestion in humans.[11]

Absorption compared to L-carnitine[edit]

It has been claimed ALCAR is superior to L-carnitine in terms of bioavailability.[2][12] Both use the same mechanism for intestinal absorption that improves with sodium.[13] One study shows ALCAR has a lower blood concentration in humans after ingestion[14] possibly because ALCAR is hydrolyzed more in blood.[15]

Health effects[edit]

ALCAR has the ability to cross the blood–brain barrier and enter the brain, where it acts as an antioxidant.[16] Its supplementation has been shown to be neuroprotective in instances of cerebral ischaemia in rats[17] and may be useful in treating peripheral nerve injury as well as spinal cord injury.[18][19] It has been shown to be of benefit to Alzheimer's patients.[20][21] It may have some neuroprotective benefit in the treatment of Parkinson's disease, but further research is required.[22] ALCAR is also known to increase sperm motility,[23] which describes the ability of sperm to move vigorously. Since motility is among the most important factors that help in the determination of sperm’s fertilization capability, acetyl-L-carnitine can help sperm cells move more actively, which consequently leads to the improved male fertility.

ALCAR has been shown to be more effective than tamoxifen in improving the curvature and reducing the pain and plaque sizes for men who sought treatment for their Peyronie's disease early and having low curvature deformities.[24] ALCAR has also been shown to improve insulin response.[25][26] It may induce epigenetic changes that may, in turn, give it utility as a therapeutic agent in neuropathic pain and depression.[27][28] These findings are in line with recent studies in humans that have demonstrated the efficacy of acetylcarnitine in the treatment of these conditions.[29][30][31]

In animal models of alcohol abuse, ALCAR has been shown to inhibit gastric mucosal injury, neuronal injury and general oxidative stress,[32][33] and has been proposed as a method of protecting from both negative short term and negative long-term effects of alcohol.[34][35]

References[edit]

  1. ^ "Acetyl-L-carnitine. Monograph." (PDF). Alternative Medicine Review 15 (1): 76–83. April 2010. PMID 20359271. 
  2. ^ a b c Activation and transportation of fatty acids to the mitochondria via the carnitine shuttle.
  3. ^ Zeyner A, Harmeyer J (1999). "Metabolic functions of L-carnitine and its effects as feed additive in horses. A review". Archiv Für Tierernährung 52 (2): 115–38. PMID 10548966. 
  4. ^ Longnus SL, Wambolt RB, Barr RL, Lopaschuk GD, Allard MF (October 2001). "Regulation of myocardial fatty acid oxidation by substrate supply". American Journal of Physiology. Heart and Circulatory Physiology 281 (4): H1561–7. PMID 11557544. 
  5. ^ Lysiak W, Lilly K, DiLisa F, Toth PP, Bieber LL (January 1988). "Quantitation of the effect of L-carnitine on the levels of acid-soluble short-chain acyl-CoA and CoASH in rat heart and liver mitochondria". The Journal of Biological Chemistry 263 (3): 1151–6. PMID 3335535. 
  6. ^ Kiens B (January 2006). "Skeletal muscle lipid metabolism in exercise and insulin resistance". Physiological Reviews 86 (1): 205–43. doi:10.1152/physrev.00023.2004. PMID 16371598. 
  7. ^ Lopaschuk GD, Gamble J (October 1994). "The 1993 Merck Frosst Award. Acetyl-CoA carboxylase: an important regulator of fatty acid oxidation in the heart". Canadian Journal of Physiology and Pharmacology 72 (10): 1101–9. PMID 7882173. 
  8. ^ Giancaterini A, De Gaetano A, Mingrone G, et al. (June 2000). "Acetyl-L-carnitine infusion increases glucose disposal in type 2 diabetic patients". Metabolism: Clinical and Experimental 49 (6): 704–8. doi:10.1053/meta.2000.6250. PMID 10877193. 
  9. ^ Mingrone G, Greco AV, Capristo E, et al. (February 1999). "L-carnitine improves glucose disposal in type 2 diabetic patients". Journal of the American College of Nutrition 18 (1): 77–82. PMID 10067662. 
  10. ^ Stephens FB, Constantin-Teodosiu D, Greenhaff PL (June 2007). "New insights concerning the role of carnitine in the regulation of fuel metabolism in skeletal muscle". The Journal of Physiology 581 (Pt 2): 431–44. doi:10.1113/jphysiol.2006.125799. PMC 2075186. PMID 17331998. 
  11. ^ Cao Y, Wang YX, Liu CJ, Wang LX, Han ZW, Wang CB (2009). "Comparison of pharmacokinetics of L-carnitine, acetyl-L-carnitine and propionyl-L-carnitine after single oral administration of L-carnitine in healthy volunteers". Clinical and Investigative Medicine 32 (1): E13–9. PMID 19178874. 
  12. ^ Jane Higdon, Ph.D. (October 2002). L-Carnitine. Linus Pauling Institute at Oregon State University. 
  13. ^ Hamilton JW, Li BU, Shug AL, Olsen WA (July 1986). "Carnitine transport in human intestinal biopsy specimens. Demonstration of an active transport system". Gastroenterology 91 (1): 10–6. PMID 3710058. 
  14. ^ Eder K, Felgner J, Becker K, Kluge H (January 2005). "Free and total carnitine concentrations in pig plasma after oral ingestion of various L-carnitine compounds". International Journal for Vitamin and Nutrition Research 75 (1): 3–9. doi:10.1024/0300-9831.75.1.3. PMID 15830915. 
  15. ^ Rebouche CJ (November 2004). "Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism". Annals of the New York Academy of Sciences 1033: 30–41. doi:10.1196/annals.1320.003. PMID 15591001. 
  16. ^ Barhwal K, Hota SK, Jain V, Prasad D, Singh SB, Ilavazhagan G (June 2009). "Acetyl-l-carnitine (ALCAR) prevents hypobaric hypoxia-induced spatial memory impairment through extracellular related kinase-mediated nuclear factor erythroid 2-related factor 2 phosphorylation". Neuroscience 161 (2): 501–14. doi:10.1016/j.neuroscience.2009.02.086. PMID 19318118. 
  17. ^ Al-Majed AA, Sayed-Ahmed MM, Al-Omar FA, Al-Yahya AA, Aleisa AM, Al-Shabanah OA (August 2006). "Carnitine esters prevent oxidative stress damage and energy depletion following transient forebrain ischaemia in the rat hippocampus". Clinical and Experimental Pharmacology & Physiology 33 (8): 725–33. doi:10.1111/j.1440-1681.2006.04425.x. PMID 16895547. 
  18. ^ Wilson AD, Hart A, Brännström T, Wiberg M, Terenghi G (2007). "Delayed acetyl-L-carnitine administration and its effect on sensory neuronal rescue after peripheral nerve injury". Journal of Plastic, Reconstructive & Aesthetic Surgery 60 (2): 114–8. doi:10.1016/j.bjps.2006.04.017. PMID 17223507. 
  19. ^ Samir P. Patel, Patrick G. Sullivan, Travis S. Lyttle, Alexander G. Rabchevsky (2010). "Acetyl-l-carnitine ameliorates mitochondrial dysfunction following contusion spinal cord injury". Journal of Neurochemistry 114 (1): 291–301. doi:10.1111/j.1471-4159.2010.06764.x. PMC 2897952. PMID 20438613. 
  20. ^ . PMID 1944900.  Missing or empty |title= (help)
  21. ^ . doi:10.1111/j.1753-4887.1992.tb01306.x.  Missing or empty |title= (help)
  22. ^ Beal MF (2003). "Bioenergetic approaches for neuroprotection in Parkinson's disease". Annals of Neurology 53 (Suppl 3): S39–47; discussion S47–8. doi:10.1002/ana.10479. PMID 12666097. 
  23. ^ Hathcock JN, Shao A (October 2006). "Risk assessment for carnitine". Regulatory Toxicology and Pharmacology 46 (1): 23–8. doi:10.1016/j.yrtph.2006.06.007. PMID 16901595. 
  24. ^ Claudio Teloken, Tulio Graziottin & Patrick E. Teloken (2007). "Oral Therapy for Peyroni's Disease". In Laurence A. Levine M.D. FACS. Peyronies Disease: A Guide to Clinical Management. Humana Press. ISBN 978-1-58829-614-6. Retrieved 2009-06-26. 
  25. ^ Ruggenenti P, Cattaneo D, Loriga G, et al. (September 2009). "Ameliorating hypertension and insulin resistance in subjects at increased cardiovascular risk: effects of acetyl-L-carnitine therapy". Hypertension 54 (3): 567–74. doi:10.1161/HYPERTENSIONAHA.109.132522. PMID 19620516. 
  26. ^ Zhang Z, Zhao M, Li Q, Zhao H, Wang J, Li Y (January 2009). "Acetyl-l-carnitine inhibits TNF-alpha-induced insulin resistance via AMPK pathway in rat skeletal muscle cells". FEBS Letters 583 (2): 470–4. doi:10.1016/j.febslet.2008.12.053. PMID 19121314. 
  27. ^ Nasca, C; Xenos, D; Barone, Y Caruso, A; Scaccianoce, S; Matrisciano, F; Battaglia, G; Mathé, AA; Pittaluga, A; Lionetto, L; Simmaco, M; Nicoletti, F (March 2013). "l-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors". Proceedings of the National Academy of Sciences of the United States of America 110 (12): 4804–4809. doi:10.1073/pnas.1216100110. PMC 3607061. PMID 23382250. 
  28. ^ Chiechio, S; Copani, A; De Petris, L; Morales, ME; Nicoletti, F; Gereau, RW (June 2006). "Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-kappaB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of L-acetylcarnitine". Molecular Pain 2 (1): 20. PMC 1550235. PMID 16764720. 
  29. ^ Chiechio, S; Copani, A; Nicoletti, F; Gereau Rw, 4th (2006). "L-acetylcarnitine: A proposed therapeutic agent for painful peripheral neuropathies". Current neuropharmacology 4 (3): 233–7. PMC 2430690. PMID 18615142.  edit
  30. ^ Chiechio, S; Copani, A; Gereau RW, 4th; Nicoletti, F (2007). "Acetyl-L-carnitine in neuropathic pain: experimental data.". CNS drugs. 21 Suppl 1: 31–8; discussion 45–6. doi:10.2165/00023210-200721001-00005. PMID 17696591. 
  31. ^ Nasca, C; Xenos, D; Barone, Y; Caruso, A; Scaccianoce, S; Matrisciano, F; Battaglia, G; Mathé, A. A.; Pittaluga, A; Lionetto, L; Simmaco, M; Nicoletti, F (2013). "L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors". Proceedings of the National Academy of Sciences 110 (12): 4804–9. doi:10.1073/pnas.1216100110. PMC 3607061. PMID 23382250.  edit
  32. ^ Rump, TJ; Abdul Muneer, PM; Szlachetka, AM; Lamb, A; Haorei, C; Alikunju, S; Xiong, H; Keblesh, J; Liu, J; Zimmerman, MC; Jones, J; Donohue TM, Jr; Persidsky, Y; Haorah, J (November 2010). "Acetyl-L-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain.". Free radical biology & medicine 49 (10): 1494–504. doi:10.1016/j.freeradbiomed.2010.08.011. PMID 20708681. 
  33. ^ Dokmeci, D; Akpolat, M; Aydogdu, N; Doganay, L; Turan, F. N. (2005). "L-carnitine inhibits ethanol-induced gastric mucosal injury in rats". Pharmacological reports : PR 57 (4): 481–8. PMID 16129915.  edit
  34. ^ Haorah, J; Floreani, N. A.; Knipe, B; Persidsky, Y (2011). "Stabilization of superoxide dismutase by acetyl-l-carnitine in human brain endothelium during alcohol exposure: Novel protective approach". Free Radical Biology and Medicine 51 (8): 1601–9. doi:10.1016/j.freeradbiomed.2011.06.020. PMC 3384514. PMID 21782933.  edit
  35. ^ Abdul Muneer, P. M.; Alikunju, S; Szlachetka, A. M.; Haorah, J (2011). "Inhibitory effects of alcohol on glucose transport across the blood-brain barrier leads to neurodegeneration: Preventive role of acetyl-L: -carnitine". Psychopharmacology 214 (3): 707–18. doi:10.1007/s00213-010-2076-4. PMC 3055928. PMID 21079922.  edit

Further reading[edit]

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