Methionine carnitine synthesis

Carnitine can be synthesized from lysine and methionine, but synthesis is decreased in premature infants. Low carnitine levels can occur in premature infants receiving parenteral nutrition or carnitine-free diets. 

Carnitine is synthesized from lysine and methionine by the pathway shown in Figure 14.2 (Vaz and Wanders, 2002). The synthesis of carnitine involves the stepwise methylation of a protein-incorporated lysine residue at the expense of methionine to yield a trimethyllysine residue. Free trimethyllysine is then released by proteolysis. It is not clear whether there is a specific precursor protein for carnitine synthesis, because trimethyllysine occurs in a number of proteins, including actin, calmodulin, cytochrome c, histones, and myosin. 

Several metabolic pathways (e.g. hpid metabohsm, creatine and carnitine synthesis) require methyl groups and these can be snppUed by choline or methionine. During the process of transmethylation, betaine, a tertiary amine, is formed by the oxidation of choline. Betaine can be added to the diet to act as a more direct supply of methyl groups, thus sparing choUne for its other fimctions of lecithin and acetylcholine formation, and methionine for protein synthesis. Betaine occurs in sugar beet. 

As discussed in section 10.6, fatty acids are the major fuel for red muscle fibres, which are the main type involved in moderate exercise. Children who lack one or other of the enzymes required for carnitine synthesis, and are therefore reliant on a dietary intake, have poor exercise tolerance because they have an impaired ability to transport fatty acids into the mitochondria for -oxidation. Provision of supplements of carnitine to the affected children overcomes the problem. Extrapolation from this rare clinical condition has led to the use of carnitine as a so-called ergogenic aid to improve athletic performance. A number of studies have shown that relatively large supplements of carnitine increase the muscle content of carnitine to only a small extent, and most studies have shown no significant effect on athletic performance or endurance. This is not surprising — carnitine is readily synthesized from lysine and methionine, and there is no evidence that any dietary intake is required. 

Man and other higher animals appear to be able to synthesize their total needs within the body. But the mechanism of carnitine synthesis in humans is unknown. Very likely, carnitine is synthesized in humans from lysine and methionine—two essential amino acids which are low in plant foods. 

Carnitine, L-3-hydroxy-4-(trimethylammonium)butyrate, is a water-soluble, tri-methylammonium derivative of y-amino-jS-hydroxybutyric acid, which is formed from trimethyllysine via y-butyrobetaine [40]. About 75% of carnitine is obtained from dietary intake of meat, fish, and dairy products containing proteins with trimethyllysine residues. Under normal conditions, endogenous synthesis from lysine and methionine plays a minor role, but can be stimulated by a diet low in carnitine. Carnitine is not further metabolized and is excreted in urine and bile as free carnitine or as conjugated carnitine esters [1, 41, 42]. Adequate intracellular levels of carnitine are therefore maintained by mechanisms that modulate dietary intake, endogenous synthesis, reabsorption, and cellular uptake. 

Lysine and methionine are both required for the synthesis of carnitine. This situation has sparked interest among researchers about the possibilities that a... 

The methylation cycle proceeds as follows. Methionine can be converted to S-adenosylmethionine (SAM). SAM is a universal methyl donor and is required in most or alJ methylation events occurring in the body. For example, SAM is used in the synthesis of creatine and carnitine and in the methylation of nucleic acids and proteins. With the donation of the methyl group, SAM is converted to S-ade-nosylhomocystcine (SAH), as shown in Figure 9-4. SAH is finally broken down to homocysteine, completing the methylation cycle. The point of departure of the 1-carbon unit, derived from serine, from the methylation cycle is indicated by the section symbol (g). 

Lysine, like most other AAs, is a building block of body protdns. Among the indispensable AAs, lysine is present in the greatest amounts, at 93.0 and 38 mmol/dl in tissues and serum, respectively (see Table 15.3). Carnitine, a compound responsible for transport of long-chain fatty adds into the mitochondria for oxidation, is synthesized in the liver and kidneys from lysine and methionine. Lysine is also required for collagen synthesis and may be central to bone health. - Lysine s effects... 

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