Carnitine 271056 225809168 2008-07-15T14:37:16Z Deli nk 560563 Reverted edits by [[Special:Contributions/24.213.151.2|24.213.151.2]] ([[User talk:24.213.151.2|talk]]) to last version by Gail {{drugbox | IUPAC_name = 3-Hydroxy-4-trimethylammonio-butanoate | image = Carnitine structure.png | width = 202 | CAS_number = 541-15-1 | ATC_prefix = A16 | ATC_suffix = AA01 | ATC_supplemental = | PubChem = 10917 | DrugBank = APRD01070 | C=7 | H=15 | N=1 | O=3 | molecular_weight = 161.199 g/mol | bioavailability = < 10% | protein_bound = None | metabolism = slightly | elimination_half-life = | pregnancy_category = | legal_status = | routes_of_administration = oral and iv | excretion = Urine (> 95%) }} '''Carnitine''' is a [[Quaternary ammonium cation|quaternary ammonium compound]] biosynthesized from the [[amino acids]] [[lysine]] and [[methionine]].<ref>{{cite journal |author=Steiber A, Kerner J, Hoppel C |title=Carnitine: a nutritional, biosynthetic, and functional perspective |journal=Mol. Aspects Med. |volume=25 |issue=5-6 |pages=455–73 |year=2004 |pmid=15363636 |doi=10.1016/j.mam.2004.06.006}}</ref> In living cells, it is required for the transport of [[fatty acid]]s from the [[cytosol]] into the [[mitochondria]] during the breakdown of [[lipid]]s (or fats) for the generation of metabolic energy. It is often sold as a [[nutritional supplement]]. Carnitine was originally found as a [[growth factor]] for [[mealworms]] and labeled ''vitamin Bt''. Carnitine exists in two [[stereoisomer]]s: its biologically active form is <small>L</small>-carnitine, while its [[enantiomer]], ''<small>D</small>-carnitine'', is biologically inactive.<ref>{{cite journal| title=Metabolic and mechanical effects using L- and D-carnitine in working swine hearts| author=A. J. Liedtke, S. H. Nellis, L. F. Whitesell and C. Q. Mahar | journal=Heart and Circulatory Physiology| volume=243 | pages= H691–H697| year=1982| url=http://ajpheart.physiology.org/cgi/content/abstract/243/5/H691| issue=5| pmid=7137362}}</ref> ==Production== In animals, carnitine is biosynthesized primarily in the [[liver]] and [[kidney]]s from the amino acids [[lysine]] or [[methionine]].<ref>{{cite web |url=http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/lca_0060.shtml |title=L-Carnitine |accessdate=2007-06-01 |format= |work=}}</ref> [[Vitamin C]] ([[ascorbic acid]]) is essential to the synthesis of carnitine. During [[human development (biology)|growth]] or [[pregnancy]] the requirement of carnitine might exceed its natural production.{{Fact|date=May 2008}} == Role in fatty acid metabolism == Carnitine transports long-chain acyl groups from fatty acids into the [[mitochondrial matrix]], so that they can be broken down through [[beta-oxidation|β-oxidation]] to [[acetate]] to obtain usable energy via the [[citric acid cycle]]. In some organisms such as fungi, the acetate is used in the [[glyoxylate cycle]] for [[gluconeogenesis]] and formation of [[carbohydrate]]s. Fatty acids must be activated before binding to the carnitine molecule to form ''acyl-carnitine''. The free fatty acid in the cytosol is attached with a [[thioester]] bond to [[coenzyme A]] (CoA). This reaction is catalyzed by the enzyme [[fatty acyl-CoA synthetase]] and driven to completion by [[pyrophosphatase|inorganic pyrophosphatase]]. The acyl group on CoA can now be transferred to carnitine and the resulting acyl-carnitine transported into the mitochondrial [[matrix (biology)|matrix]]. This occurs via a series of similar steps: # Acyl-CoA is conjugated to carnitine by [[carnitine acyltransferase I]] (palmitoyltransferase) located on the outer mitochondrial membrane # Acyl-carnitine is shuttled inside by a [[carnitine-acylcarnitine translocase]] # Acyl-carnitine is converted to acyl-CoA by [[carnitine acyltransferase II]] (palmitoyltransferase) located on the inner mitochondrial membrane. The liberated carnitine returns to the cytosol. Human genetic disorders such as [[primary carnitine deficiency]], [[carnitine palmitoyltransferase I deficiency]], [[carnitine palmitoyltransferase II deficiency]] and [[carnitine-acylcarnitine translocase deficiency]] affect different steps of this process.<ref>{{cite journal |author=Olpin S |title=Fatty acid oxidation defects as a cause of neuromyopathic disease in infants and adults |journal=Clin. Lab. |volume=51 |issue=5-6 |pages=289–306 |year=2005 |pmid=15991803}}</ref> Carnitine acyltransferase I undergoes [[allosteric]] inhibition as a result of [[malonyl-CoA]], an intermediate in fatty acid biosynthesis, in order to prevent futile cycling between β-oxidation and fatty acid synthesis. <center>[[Image:Acyl-CoA from cytosol to the mitochondrial matrix.gif|Click to enlarge]]</center> ==Effects on bone mass== In the course of human aging, carnitine concentration in cells diminishes affecting fatty acid metabolism in various tissues. Particularly adversely affected are bones which require continuous reconstructive and metabolic functions of osteoblasts for maintenance of bone mass. There is a close correlation between changes in plasma levels of [[osteocalcin]] and [[osteoblast]] activity and a reduction in osteocalcin plasma levels is an indicator of reduced osteoblast activity,<ref>Claudio Cavazza, ''Composition for the Prevention and Treatment of Osteoporosis due to Menopause Syndrome'' (2002), US Patent 6,335,038, column 4.</ref> which appears to underlie [[osteoporosis]] in elderly subjects and in postmenopausal women. Administration of a carnitine mixture or propionyl-<small>L</small>-carnitine is capable of increasing serum osteocalcin concentrations of animals thus treated, whereas serum osteocalcin levels tend to decrease with age in control animals.<ref>Claudio Cavazza, ''Composition for the Prevention and Treatment of Osteoporosis due to Menopause Syndrome'' (2002), US Patent 6,335,038, columns 3-4.</ref> ==Antioxidant effects== The carnitines exert a substantial [[antioxidant]] action, thereby providing a protective effect against lipoperoxidation of phospholipid membranes and against oxidative stress induced at the myocardial and endothelial cell level. <ref>Claudio Cavazza, ''Composition for the Prevention and Treatment of Osteoporosis due to Menopause Syndrome'' (2002), US Patent 6,335,038, column 3.</ref> ==Effects on diabetes== <small>L</small>-Carnitine improved glucose disposal among 15 patients with [[type II diabetes]] and 20 healthy volunteers.<ref name="AMC study">{{cite journal | title=L-Carnitine Improves Glucose Disposal in Type 2 Diabetic Patients| journal=Journal of the American College of Nutrition| author=Geltrude Mingrone, Aldo V. Greco, Esmeralda Capristo, Giuseppe Benedetti, Annalisa Giancaterini, Andrea De Gaetano, and Giovanni Gasbarrini |year=1999 |volume=18 |issue=1 |pages=77–82 |url=http://www.jacn.org/cgi/content/full/18/1/77 | pmid=10067662}}</ref> Glucose storage increased between both groups, but glucose oxidation increased only in the diabetic group. Finally, glucose uptake increased about 8% for both. == Food sources == The highest concentrations of carnitine are found in [[red meat]] and dairy products. Other natural sources of carnitine include [[Nut (fruit)|nuts]] and [[seed]]s (e.g. [[pumpkin]], [[sunflower]], [[sesame]]), [[legume]]s or [[Pulse (legume)|pulses]] ([[bean]]s, [[pea]]s, [[lentil]]s, [[peanut]]s), [[vegetables]] ([[globe artichoke|artichokes]], [[asparagus]], [[beet|beet greens]], [[broccoli]], [[brussels sprouts]], [[collard greens]], [[garlic]], [[Mustard plant#Mustard greens|mustard greens]], [[okra]], [[parsley]]), [[fruit]]s ([[apricot]]s, [[banana]]s), [[cereal]]s ([[buckwheat]], [[maize|corn]], [[millet]], [[oatmeal]], rice [[bran]], [[rye]], [[whole wheat]], wheat [[bran]], [[wheat germ]]) and other 'health' foods ([[bee pollen]], [[brewer's yeast]], [[carob]], and [[kale]]). {{Fact|date=May 2008}} {| class="wikitable" |- | '''Product''' || '''Quantity''' || '''Carnitine''' |- | Beef Steak || 3.5 oz || 95 mg |- | Ground Beef || 3.5 oz || 94 mg |- | Pork || 3.5 oz || 27.7 mg |- | Bacon || 3.5 oz || 23.3 mg |- | [[Tempeh]] || half cup || 19.5 mg |- | Cod Fish || 3.5 oz || &nbsp;5.6 mg |- | Chicken Breast || 3.5 oz || &nbsp;3.9 mg |- | American Cheese || 3.5 oz || &nbsp;3.7 mg |- | Ice Cream || 3.5 fl oz|| &nbsp;3.7 mg |- | Whole Milk || 3.5 fl oz|| &nbsp;3.3 mg |- | Avocado || one medium || 2 mg<ref>[http://lpi.oregonstate.edu/infocenter/othernuts/carnitine/ Linus Pauling Institute at Oregon State University<!-- Bot generated title -->]</ref> |- | Cottage Cheese || 3.5 fl oz|| &nbsp;1.1 mg |- | Whole Wheat Bread|| 3.5 oz || &nbsp;0.36 mg |- | Asparagus || 3.5 oz || &nbsp;0.195 mg |- | White Bread || 3.5 oz || &nbsp;0.147 mg |- | Macaroni || 3.5 oz || &nbsp;0.126 mg |- | Peanut Butter || 3.5 oz || &nbsp;0.083 mg |- | Rice (cooked) || 3.5 oz || &nbsp;0.0449 mg |- | Eggs || 3.5 oz || &nbsp;0.0121 mg |- | Orange Juice || 3.5 fl oz|| &nbsp;0.0019 mg |} Generally, 20 to 200 mg/day are ingested per day by those on an [[omnivorous]] diet, while those on a strict [[vegetarian]] or [[vegan]] diet may ingest as little as 1 mg/day.{{Fact|date=April 2008}} ==Other sources== Other sources may be found in over-the-counter [[vitamins]], [[energy drink]]s and various other products. Products containing <small>L</small>-carnitine cannot be marketed as "natural health products" in [[Canada]]. <small>L</small>-Carnitine products and supplements are not allowed to be imported into Canada ([[Health Canada]]).<ref>{{cite web |url=http://www.hc-sc.gc.ca/dhp-mps/prodnatur/bulletins/communiques/communique_sep05_e.html |title=NHPD Monthly Communique, Vol. 1, Issue 1, September 2005 |accessdate=2007-06-01 |format= |work=}}</ref> ==As a weight loss supplement== "Although <small>L</small>-carnitine has been marketed as a weight-loss supplement, there is no scientific evidence to date to show that it improves weight loss. A recent study of moderately overweight women found that <small>L</small>-carnitine did not significantly alter body weight, body fat, or lean body mass. Based on the results of this one small study, claims that <small>L</small>-carnitine helps reduce weight are not supported at this time." <ref>{{cite web |url=http://www.umm.edu/altmed/articles/carnitine-l-000291.htm |title=University of Maryland Medical Centre, April 2002 |accessdate=2008-05-20|format =|work=}}</ref> == See also == * [[Acetylcarnitine]] * [[Primary carnitine deficiency]] ==References== <references/> == External links == * [http://www.umm.edu/altmed/ConsSupplements/CarnitineLCarnitinecs.html article on Carnitine] at [[University of Maryland, Baltimore|University of Maryland]] Medical Center * [http://www.chm.bris.ac.uk/motm/carnitine/Carnitine.htm Molecule of the Month] at [[University of Bristol]] {{Dietary supplement}} {{Other alimentary tract and metabolism products}} [[Category:Hydroxy acids]] [[Category:Quaternary ammonium compounds]] [[Category:Dietary supplements]] [[Category:Amino acids]] [[cs:Karnitin]] [[de:Carnitin]] [[es:Carnitina]] [[eo:Karnitino]] [[fa:کارنیتین]] [[id:Karnitin]] [[it:Carnitina]] [[lt:Karnitinas]] [[nl:Carnitine]] [[ja:カルニチン]] [[pl:Karnityna]] [[pt:Carnitina]] [[sk:Karnitín]] [[sv:Carnitin]] [[tr:Karnitin]] [[zh:左旋肉碱]]