The Methionine Load Test

The metabolism of methionine, shown in Figure 9.5, includes two pyridoxal phosphate-dependent steps: cystathionine synthetase and cystathionase. Cystathionine synthetase is little affected by vitamin B6 deficiency, presumably because it has a high affinity for its cofactor, and possibly also a slow rate of turnover. However, cystathionase activity falls in vitamin B6 deficiency, and there is an increase in the tissue content of inactive apoenzyme. The result of this is that in vitamin B6 deficiency there is an increase in the urinary excretion of cystathionine, both alter a loading dose of methionine and under basal conditions, suggesting that methionine metabolism provides a useful index of status.

As discussed in Section, the metabolic fate of homocysteine arising from methionine is determined not only by the activity of cystathionine synthetase and cystathionase, but also the rate at which it is remethylated to methionine (which is dependent on vitamin B12 and folate status) and the requirement for cysteine.

It is apparent that abnormally increased excretion of homocysteine and cystathionine metabolites after a test dose of methionine cannot necessarily be regarded as evidence of vitamin B6 deficiency. This means that, like the tryptophan load test, the methionine load test is unreliable as an index of status in epidemiological studies, although it is (probably) reliable in depletion/ repletion studies to determine requirements.


Vitamin B6 requirements have been estimated both by isotopic tracer studies to determine turnover of the body pool (Section 9.6.1) and also by depletion/ repletion studies using a variety of indices of status (Section 9.6.2). These studies have generally been conducted on young adults, and there is inadequate information to determine the requirements of elderly people, because apparent status assessed by a variety of indices declines with increasing age, despite intake as great as in younger people (Bates et al., 1999a). As discussed in Section 9.6.3, there is also inadequate information to estimate the requirements of infants.

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