Relationship of Methionine with Other Methyl Donors

In addition to its primary function as a constituent of proteins, methionine can be converted into S-adenosylmethionine and S-adenosylhomocysteine, as illustrated in Fig. 8.3. These reactions release a methyl group that is used in several metabolic processes, primarily DNA methylation and synthesis of carnitine from lysine, adrenaline from noradrenaline, and creatine from guanidine acetate (Simon, 1999). Thus, methionine is sometimes referred to as a 'methyl donor'. To regenerate methionine from homocysteine, a methyl group must be transferred back via either the tetrahydrofo-late pathway (involving folates and vitamin B12) or the betaine pathway (Fig. 8.6). Betaine can be produced from choline by an irreversible two-step oxidation reaction that occurs in liver and kidney.

Homocysteine

5-Methyltetrahydrofolate

Vitamin B.

Tetrahyd rotolate

Tetrahyd rotolate

Betaine

Betaine aldehyde Choline

Dimethylglycine

Methionine

Fig. 8.6. Two metabolic pathways for the conversion of homocysteine into methionine.

The notion that some of the methionine requirement could be spared or reduced by increasing the intake of choline or betaine has attracted attention for several years. The idea is appealing because replacement of dl-methionine or protein sources with betaine, which is commercially available to the feed industry (Danisco, 2001), could reduce diet costs. Unfortunately, experiments with pigs have not been encouraging. Simon (1999) reviewed ten papers and abstracts, published between 1990 and 1998, in which betaine was supplemented in pig diets. The conclusions reached in this review were that 'in none of these studies did supplementation with betaine (1.0-1.25 g kg-1) exert any consistent and significant effect on growth or carcass traits' and 'under normal conditions, carcass traits cannot be improved in pigs by adding extra betaine or choline to the diets during the finishing period'. Since the review by Simon (1999) several additional papers (Emmert et ai, 1998; Matthews et al., 1998, 2001a,b,c; 0verland et ai, 1999) and abstracts (Casarin et al., 1997; Hall et al., 1997; Cromwell et al., 1999, 2000; Kitt et al., 1999, 2000; Pettey et al., 2001; Schrama et al., 2001) have reported experiments in which the effects of betaine have been evaluated in terms of growth, carcass traits, and pork quality measures. Although positive effects have been observed in some experiments, results have been variable and inconsistent. Furthermore, few of the experiments have been designed to measure directly whether betaine can substitute for a portion of the methionine requirement. Kitt et al. (2000) attempted to do this, but were unable to demonstrate a response to added methionine and therefore unable to evaluate the effect of betaine. The paper by Matthews et al. (2001c) seems to be the only report in which a direct comparison of the replacement value of betaine for methionine is possible. In a diet that was shown to be limiting in methionine, supplemental betaine did increase weight gain. However, the response was due to an increase in feed intake and therefore sulphur amino acid intake. The authors concluded that betaine did not spare methionine in their experiment. Thus, although supplementation of pig diets with betaine has been shown to be beneficial in some situations, the effects are probably not due to methionine sparing, but are more likely due to other factors such as effects on osmoregulation or energy metabolism. Normal pig diets that are adequately supplemented with choline should contain adequate amounts of methyl donors.

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