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Carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine.[1] In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids (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 stereoisomers: its biologically active form is L-carnitine, while its enantiomer, D-carnitine, is biologically inactive.[2]
Production
In animals, carnitine is biosynthesized primarily in the liver and kidneys from the amino acids lysine or methionine.[3] Vitamin C (ascorbic acid) is essential to the synthesis of carnitine. During growth or pregnancy the requirement of carnitine might exceed its natural production.[citation needed]
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 ฿-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 carbohydrates. 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 inorganic pyrophosphatase.
The acyl group on CoA can now be transferred to carnitine and the resulting acyl-carnitine transported into the mitochondrial 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.[4]
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 ฿-oxidation and fatty acid synthesis.
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,[5] which appears to underlie osteoporosis in elderly subjects and in postmenopausal women. Administration of a carnitine mixture or propionyl-L-carnitine is capable of increasing serum osteocalcin concentrations of animals thus treated, whereas serum osteocalcin levels tend to decrease with age in control animals.[6]
Antioxidant effects
The carnitines exert a substantial antioxidant action, thereby providing a protective effect against lipid peroxidation of phospholipid membranes and against oxidative stress induced at the myocardial and endothelial cell level. [7]
Effects on diabetes
L-Carnitine improved glucose disposal among 15 patients with type II diabetes and 20 healthy volunteers.[8] 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 nuts and seeds (e.g. pumpkin, sunflower, sesame), legumes or pulses (beans, peas, lentils, peanuts), vegetables (artichokes, asparagus, beet greens, 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 'health' foods (bee pollen, brewer's yeast, carob).[citation needed]
| 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 |
5.6 mg |
| Chicken Breast |
3.5 oz |
3.9 mg |
| American Cheese |
3.5 oz |
3.7 mg |
| Ice Cream |
3.5 fl oz |
3.7 mg |
| Whole Milk |
3.5 fl oz |
3.3 mg |
| Avocado |
one medium |
2 mg[9] |
| Cottage Cheese |
3.5 fl oz |
1.1 mg |
| Whole Wheat Bread |
3.5 oz |
0.36 mg |
| Asparagus |
3.5 oz |
0.195 mg |
| White Bread |
3.5 oz |
0.147 mg |
| Macaroni |
3.5 oz |
0.126 mg |
| Peanut Butter |
3.5 oz |
0.083 mg |
| Rice (cooked) |
3.5 oz |
0.0449 mg |
| Eggs |
3.5 oz |
0.0121 mg |
| Orange Juice |
3.5 fl oz |
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.[citation needed] No advantage appears to exist in giving an oral dose greater than 2g at one time, since absorption studies indicate saturation at this dose.[10]
Other sources
Other sources may be found in over-the-counter vitamins, energy drinks and various other products. Products containing L-carnitine cannot be marketed as "natural health products" in Canada. L-Carnitine products and supplements are not allowed to be imported into Canada (Health Canada).[11]
As a weight loss supplement
"Although L-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 L-carnitine did not significantly alter body weight, body fat, or lean body mass. Based on the results of this one small study, claims that L-carnitine helps reduce weight are not supported at this time." [12]
Regular supplements of L-carnitine, however, contribute to energy metabolism and improved neurotransmitter function in the brain.[13]
See also
References
- ^ Steiber A, Kerner J, Hoppel C (2004). "Carnitine: a nutritional, biosynthetic, and functional perspective". Mol. Aspects Med. 25 (5-6): 45573. doi:10.1016/j.mam.2004.06.006. PMID 15363636.
- ^ A. J. Liedtke, S. H. Nellis, L. F. Whitesell and C. Q. Mahar (1982). "Metabolic and mechanical effects using L- and D-carnitine in working swine hearts". Heart and Circulatory Physiology 243 (5): H691H697. PMID 7137362.
- ^ "L-Carnitine". Retrieved on 2007-06-01.
- ^ Olpin S (2005). "Fatty acid oxidation defects as a cause of neuromyopathic disease in infants and adults". Clin. Lab. 51 (5-6): 289306. PMID 15991803.
- ^ Claudio Cavazza, Composition for the Prevention and Treatment of Osteoporosis due to Menopause Syndrome (2002), US Patent 6,335,038, column 4.
- ^ Claudio Cavazza, Composition for the Prevention and Treatment of Osteoporosis due to Menopause Syndrome (2002), US Patent 6,335,038, columns 3-4.
- ^ Claudio Cavazza, Composition for the Prevention and Treatment of Osteoporosis due to Menopause Syndrome (2002), US Patent 6,335,038, column 3.
- ^ Geltrude Mingrone, Aldo V. Greco, Esmeralda Capristo, Giuseppe Benedetti, Annalisa Giancaterini, Andrea De Gaetano, and Giovanni Gasbarrini (1999). "L-Carnitine Improves Glucose Disposal in Type 2 Diabetic Patients". Journal of the American College of Nutrition 18 (1): 7782. PMID 10067662.
- ^ Linus Pauling Institute at Oregon State University
- ^ http://www.encyclopedia.com/doc/1G1-131086133.html
- ^ "NHPD Monthly Communique, Vol. 1, Issue 1, September 2005". Retrieved on 2007-06-01.
- ^ "University of Maryland Medical Centre, April 2002". Retrieved on 2008-05-20.
- ^ American Journal of Clinical Nutrition, December 2007
External links
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