carnitine

カルニチン

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/09/21 10:53:07」(JST)

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Not to be confused with carnosine or creatine.

Carnitine

Systematic (IUPAC) name
3-Hydroxy-4-(trimethylazaniumyl)butanoate
Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Legal status	?
Routes	oral and iv
Pharmacokinetic data
Bioavailability	< 10%
Protein binding	None
Metabolism	slightly
Excretion	Urine (> 95%)
Identifiers
CAS number	541-15-1 Y
ATC code	A16AA01 (L form)
PubChem	CID 288
DrugBank	DB00583
ChemSpider	282 Y
UNII	0G389FZZ9M Y
KEGG	C00318 Y
ChEBI	CHEBI:17126 Y
ChEMBL	CHEMBL172513 Y
Chemical data
Formula	C7H15NO3
Mol. mass	161.199 g/mol
SMILES C[N+](C)(C)CC(CC(=O)[O-])O
InChI InChI=1S/C7H15NO3/c1-8(2,3)5-6(9)4-7(10)11/h6,9H,4-5H2,1-3H3 Y Key:PHIQHXFUZVPYII-UHFFFAOYSA-N Y
N (what is this?)  (verify)

Carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine.

In eukaryotic cells, it is required for the transport of fatty acids from the intermembraneous space in the mitochondria, into the mitochondrial matrix during the breakdown of lipids (fats) for the generation of metabolic energy. It is widely available as a nutritional supplement. Carnitine was originally found as a growth factor for mealworms and labeled vitamin B_T, although carnitine is not a proper vitamin. Carnitine exists in two stereoisomers: its biologically active form is L-carnitine, whereas its enantiomer, D-carnitine, is biologically inactive.

Biometrical Calcutations

Biosynthesis

Main article: carnitine biosynthesis

In animals, the biosynthesis of carnitine occurs primarily in the liver and kidneys from the amino acids lysine (via trimethyllysine) and methionine. Vitamin C (ascorbic acid) is not essential to the synthesis of carnitine.

Role in fatty acid metabolism

Carnitine transports long-chain acyl groups from fatty acids into the mitochondrial matrix, so they can be broken down through β-oxidation to acetyl CoA 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 carbohydrates. Fatty acids must be activated before binding to the carnitine molecule to form 'acylcarnitine'. 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 inorganic pyrophosphatase.

The acyl group on CoA can now be transferred to carnitine and the resulting acylcarnitine transported into the mitochondrial matrix. This occurs via a series of similar steps:

1. Acyl CoA is transferred to the hydroxyl group of carnitine by carnitine acyltransferase I (palmitoyltransferase) located on the outer mitochondrial membrane
2. Acylcarnitine is shuttled inside by a carnitine-acylcarnitine translocase
3. Acylcarnitine 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.

Carnitine acyltransferase I and peroxisomal carnitine octanoyl transferase (CROT) undergo allosteric inhibition as a result of malonyl-CoA, an intermediate in fatty acid biosynthesis, to prevent futile cycling between β-oxidation and fatty acid synthesis.

Physiological effects

Atherosclerosis

Main article: Trimethylamine N-oxide

There may be a link between dietary consumption of carnitine and atherosclerosis, but there is also evidence that it lowers the risk of mortality and arrythmias after an acute myocardial infarction.

When certain species of intestinal bacteria were exposed to carnitine from food, they produced a waste product, trimethylamine, which is transformed in the liver to trimethylamine N-oxide (TMAO). TMAO may be associated with atherosclerosis. The presence of large amounts of TMAO-producing bacteria was a consequence of a long-term diet rich in meat. However, when the authors compared the risk of cardiovascular events to the levels of carnitine and TMAO, they found that the risk was higher in those with higher TMAO levels, independent of the carnitine levels.

Vegetarian and vegans who ate a single meal of meat had much lower levels of TMAO in their bloodstream than did regular meat-eaters, as vegetarian and vegans had lower levels of the intestinal bacteria that converts carnitine into TMAO.

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.

Effect on thyroid hormone action

A 2004 study found that L-carnitine acts as a peripheral antagonist of thyroid hormone action. In particular, L-carnitine inhibits both triiodothyronine (T3) and thyroxine (T4) entry into the cell nuclei.

Possible health effects

Carnitine has been proposed as a supplement to treat a variety of health conditions including heart attack, heart failure, angina, narcolepsy, and diabetic neuropathy, but not fatigue, improving exercise performance, nor wasting syndrome (weight loss). In all of these cases, both positive and negative findings, the results are preliminary, proposed, and not part of routine treatment.

There is also some suggestion that use of carnitine may improve sperm motility in men with sperm problems.

Sources

Food

The highest concentrations of carnitine are found in red meat and dairy products. Carnitine can be found at significantly lower levels in many other foods including nuts and seeds (e.g. pumpkin, sunflower, sesame), legumes or pulses (beans, peas, lentils, peanuts), vegetables (artichokes, asparagus, beet greens (young leaves of the beetroot), broccoli, brussels sprouts, collard greens, garlic, mustard greens, okra, parsley, kale), fruits (apricots, bananas), cereals (buckwheat, corn, millet, oatmeal, rice bran, rye, whole wheat, wheat bran, wheat germ) and other foods (bee pollen, brewer's yeast, carob).

Product	Quantity	Carnitine
Beef steak	100 g	95 mg
Ground beef	100 g	94 mg
Pork	100 g	27.7 mg
Bacon	100 g	23.3 mg
Tempeh	100 g	19.5 mg
Cod fish	100 g	5.6 mg
Chicken breast	100 g	3.9 mg
American cheese	100 g	3.7 mg
Ice cream	100 ml	3.7 mg
Whole milk	100 ml	3.3 mg
Avocado	one medium	2 mg
Cottage cheese	100 g	1.1 mg
Whole-wheat bread	100 g	0.36 mg
Asparagus	100 g	0.195 mg
White bread	100 g	0.147 mg
Macaroni	100 g	0.126 mg
Peanut butter	100 g	0.083 mg
Rice (cooked)	100 g	0.0449 mg
Eggs	100 g	0.0121 mg
Orange juice	100 ml	0.0019 mg

In general, 20 to 200 mg are ingested per day by those on an omnivorous diet, whereas those on a strict vegetarian or vegan diet may ingest as little as 1 mg/day. No advantage appears to exist in giving an oral dose greater than 2 g at one time, since absorption studies indicate saturation at this dose.

Health Canada

Other sources may be found in over-the-counter vitamins, energy drinks and various other products. Products containing L-carnitine can now be marketed as "natural health products" in Canada. As of 2012, Parliament has allowed carnitine products and supplements to be imported into Canada (Health Canada). The Canadian government did issue an amendment in December 2011 allowing the sale of L-carnitine without a prescription.

See also

• Acetylcarnitine
• Gamma-butyrobetaine dioxygenase
• Meldonium

References

External links

• Molecule of the Month at University of Bristol

UpToDate Contents

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English Journal

• Plasma acylcarnitines inadequately reflect tissue acylcarnitine metabolism.

• Schooneman MG1, Achterkamp N2, Argmann CA3, Soeters MR2, Houten SM4.
• Biochimica et biophysica acta.Biochim Biophys Acta.2014 Jul;1841(7):987-94. doi: 10.1016/j.bbalip.2014.04.001. Epub 2014 Apr 18.
• Acylcarnitines have been linked to obesity-induced insulin resistance. However the majority of these studies have focused on acylcarnitines in plasma. It is currently unclear to what extent plasma levels of acylcarnitines reflect tissue acylcarnitine metabolism. We investigated the correlation of pl
• PMID 24747043

• Inhibition of ATP citrate lyase induces triglyceride accumulation with altered fatty acid composition in cancer cells.

• Migita T1, Okabe S, Ikeda K, Igarashi S, Sugawara S, Tomida A, Soga T, Taguchi R, Seimiya H.
• International journal of cancer. Journal international du cancer.Int J Cancer.2014 Jul 1;135(1):37-47. doi: 10.1002/ijc.28652. Epub 2013 Dec 18.
• De novo lipogenesis is activated in most cancers and several lipogenic enzymes have been implicated as therapeutic targets. Here, we demonstrate a novel function of the lipogenic enzyme, ATP citrate lyase (ACLY), in lipid metabolism in cancer cells. ACLY depletion by small interfering RNAs caused gr
• PMID 24310723

• Choline acetyltransferase and organic cation transporters are responsible for synthesis and propionate-induced release of acetylcholine in colon epithelium.

• Bader S1, Klein J2, Diener M3.
• European journal of pharmacology.Eur J Pharmacol.2014 Jun 15;733:23-33. doi: 10.1016/j.ejphar.2014.03.036. Epub 2014 Mar 31.
• Acetylcholine is not only a neurotransmitter, but is found in a variety of non-neuronal cells. For example, the enzyme choline acetyltransferase (ChAT), catalyzing acetylcholine synthesis, is expressed by the colonic epithelium of different species. These cells release acetylcholine across the basol
• PMID 24698650

Japanese Journal

• CEU Quiz関連記事 サプリメントには他に何が含まれているか? マルチ成分サプリメント中の補助成分による筋力、パワー、回復の改善効果に関するレビュー

• Strength & conditioning journal : 日本ストレングス&コンディショニング協会機関誌 22(10), 24-39, 2015-12
• NAID 40020661638

• Metabolic autopsy with next generation sequencing in sudden unexpected death in infancy: Postmortem diagnosis of fatty acid oxidation disorders

• Molecular Genetics and Metabolism Reports 5, 26-32, 2015-12
• NAID 120005676317

• バルプロ酸ナトリウム (特集 抗てんかん薬と精神科臨床)

• 精神科治療学 30(8), 1059-1065, 2015-08
• NAID 40020647830

Related Links

• Carnitine — Health Professional Fact Sheet

Click here for more information. ... References Rebouche CJ. Carnitine. In: Modern Nutrition in Health and Disease, 9th Edition (edited by Shils ME, Olson JA, Shike M, Ross, AC). Lippincott Williams and Wilkins, New York, 1999 ...

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L-カルニチンの基本知識、摂り方、安全性、活用法などの情報を、L-カルニチンのトップメーカー・ロンザジャパンより発信中。 ... L-カルニチンとはエネルギー代謝に必須の栄養素です。筋肉細胞における脂肪酸のミトコンドリアへの ...

Related Pictures

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★リンクテーブル★

リンク元	「カルニチン」
拡張検索	「carnitine acyltransferase」「acetylcarnitine」

「カルニチン」

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英

carnitine

同

ビタミンBT vitamin BT

化

塩化カルニチン carnitine chloride

商

アベダイン、エントミン

関

カルニチンパルミトイルトランスフェラーゼ

• (CH3)3N＋CH2CH(OH)CH2COO－、C7H15NO3。

「carnitine acyltransferase」

　　[★]

カルニチンアシル基転移酵素、カルニチンアシルトランスフェラーゼ

「acetylcarnitine」

　　[★]

アセチルカルニチン