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Carnitina un osmolito muy importante para la oxidacion mitocondrial de acidos grasos.



The name carnitine originates from the Latin word for flesh or meat, carno. It was discovered in 1905 by Gulewitsch and Krimberg (1), and Kutscher; quoted by Fraenkel and Friedman (2) from muscle extracts and the molecular structure (3-hydroxy-4-N-trimethyl-aminobutyric acid), was established by Tomita and Sendju in 1927; quoted by Fraenkel and Friedman (2).

Work in the 1950s showed that carnitine was essential for the growth of the yellow mealworm Tenebrio molitor (3, 4); that carnitine was present in a wide range of biological materials (5); and that carnitine could be reversibly acetylated with acetyl-coenzyme A (CoA) (6).


Carnitine synthesis in mammals is carried out from the turnover of proteins containing lysine residues which are previously posttranslationally trimethylated with release of trimethyllysine (7-18). The rate-limiting step in the pathway is the hepatic enzyme, gbutyrobetaine hydroxylase, however the rate of carnitine biosynthesis is mainly determined by the rate of protein turnover which supplies trimethyllysine (19) (Figure 1).

Carnitine is present in tissues and body fluids as free and as the esterified short-chain and longchain acylcarnitines (20, 21). Total carnitine consists of the sum of free carnitine and all acylcarnitines. Animal tissues contain relatively high amounts of carnitine, varying between 0.2 and 6 umol/g, with the highest concentrations in heart and skeletal muscle (22-25).

In humans 98% of the carnitine resides in the skeletal and cardiac muscle with 1.6% in the liver and kidney, and 0.4% in the extra cellular fluid (26). Humans obtain most of their carnitine (some 50% to 75% of daily requirements) through dietary intake (meat, poultry, fish and diary products); with L-carnitine being synthesised in primarily the liver and also in the kidney from proteinderived 6-N-trimethyllysine via 3-hydroxy-6N-trimethyllysine,4-N- trimethylaminobutyraldehyde and 4-N trimethylaminobutyrate (4-N-butyrobetaine) (27). Other cells depend on carnitine import via active uptake from the blood. This transport system is also involved in the renal tubular reabsorption and intestinal absorption of carnitine.

There is no degradation pathway for carnitine in mammals, although there is some minor degradation of dietary carnitine by intestinal bacteria (less than 1 to 2% in total) (28-30), and carnitine is eliminated via urine as free carnitine and acylcarnitines with renal fractional reabsorption of up to 90% (31). Carnitine uptake into tissues and cells occurs by a saturable sodium-dependent transport mechanism (32), and a failure of its transport mechanism leads to systemic or primary carnitine deficiency associated with low levels of free and total carnitine in tissues and plasma. Also, during periods of metabolic decompensation in which acyl-CoA esters accumulate, the concentration of acylcarnitines greatly increases and exceeds the capacity for L-carnitine biosynthesis (and of dietary sources) leading to a secondary carnitine deficiency (33, 34).


The role of carnitine in fatty acid oxidation was discovered by Fritz in 1955 (35) working with liver homogenates, and the configuration of the physiological enantiomer was determined as L(-) or R(-)-3-hydroxy-4N,N,N-trimethylaminobutyrate by Kaneko and Yoshida in 1962 (36).


The main function of carnitine is to shuttle activated long-chain fatty acids [fatty acylcoenzyme A (CoA)] from the cytosol into the mitochondrial matrix for b-oxidation, and to remove short-chain, medium-chain and long chain fatty acids, that accumulate as a result of normal and abnormal metabolism (37). Hence carnitine helps to maintain adequate cellular levels of free CoA. Furthermore, products of the peroxisomal b-oxidation system, including acetyl-CoA, are transported as carnitine-esters from peroxisomes to mitochondria for complete degradation to C[O.sub.2] and [H.sub.2]O (38). Carnitine can also modulate the toxic effects of poorly metabolised acyl-groups of either xenobiotic origin (e.g. pivalic acid and valproate) or those arising from various inborn errors of metabolism, and it can also interact with membranes to change their physiochemical properties (39). This means that carnitine modulates the acyl-CoA/free CoA ratio via the formation of acyl-carnitines. If acyl-CoAs are produced faster than they are utilised, intramitochondrial free CoA is regenerated as carnitine, which binds the acylgroups, thus restoring the normal intramitochondrial acyl-CoA/free CoA ratio (37, 40-42).


The measurement of free and total carnitine is an important tool for the investigation of patients suspected to have an abnormal condition related to carnitine metabolism. The list of protocols to measure carnitine started in 1953, with a bioassay published by Fraenkel, followed by a method using bromophenol blue (43), and from then several improvements have been made.

Since carnitine is a vehicle by which the acyl groups can leave the mitochondria and there is equilibrium between acylcarnitines and their respective CoA thioesters, the analysis of carnitine and acylcarnitines in blood is approximately equivalent to the analysis of acyl-CoAs in the mitochondria. The concept of an acylcarnitine profile rather than a urine organic acid profile was therefore indicated as a potentially more valuable diagnostic tool for the disorders of branched-chain amino acid and fatty acid catabolism (44).

Acylcarnitine identification in body fluids using tandem mass spectrometry (MS/MS) was developed in the late 1980s (44-45) and represents a valuable tool for the diagnosis of some long-chain fatty acid oxidation defects which are difficult to diagnose by classical chromatographic method. The method has the potential to screen effectively for at least a dozen other disorders (46-50).

Some authors suggest that a plasma carnitine and acylcarnitine profile should be performed in all patients presenting an acute episode of hypoketotic hypoglycaemia, Reye syndrome, hypertrophic cardiomyopathy, pericardial effusion, cardiac failure or rapid unexpected death in the neonatal period or during infancy, also heart beat disorders during neonatal period, hypotonia with unexplained failure to thrive, retinitis pigmentosa or even muscle pain triggered by exercise (51). The measurement of acylcarnitines using MS/MS has been reported in whole blood (52), plasma (53), urine (54), amniotic fluid (55), and bile (56), while the analysis of free and total carnitine using tandem mass spectrometry has been somehow controversial; however recently several research groups have improved and standarized methods for the carnitine measurement using this technology (57-59).


Carnitine is a very important molecule for the metabolism of long-chain fatty acids, as it is necessary for getting acylated fatty acids into the mitochondrial matrix, however there are other important functions for carnitine. The measurements of carnitine has been improved by the use of tandem mass spectrometry as a useful tool for diagnosis and follow up of patients suffering primary and secondary carnitine deficiency.

Recibido: Septiembre 22 de 2006 - Aceptado: Septiembre 25 de 2006


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Jose Henry Osorio [1]

[1] Departamento de Ciencias Basicas de la Salud, Laboratorio de Enfermedades Metabolicas. Grupo de Investigacion Biosalud. Universidad de Caldas. Correspondence: Universidad de Caldas, Departamento de Ciencias Basicas de la Salud. Calle 65 N0. 26-10. Manizales. E-mail:
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