Carnitine - L Carnitine And Weight Loss

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 calculations

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 ?-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 ?-oxidation and fatty acid synthesis.

Physiological effects

Atherosclerosis

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.

Another study has found evidence of a second path for atherogenic activity of carnitine, passing through a different metabolite: ?-butyrobetaine (?BB)

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. A 2008 study found that supplementing with L-carnitine decreased bone turnover and increased bone mineral density in rats.

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. For this reason, L-carnitine has been proposed as a supplement to treat hyperthyroidism. A 2001 study found that L-carnitine was useful in both reversing and preventing hyperthyroid symptoms.

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 acetyl carnitine and L-arginine may improve sperm motility in men with sperm abnormalities.

Sources

Food

The highest concentrations of carnitine are found in red meat. 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).

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

Interesting Informations

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