Turnover glycogen phosphorylase

There may be multiple metabolicpoolsofthe vitamin, with very different rates of turnover. In this case, short-term and long-term smdies will give very different estimates of the fractional rate of turnover of the total body pool. As discussed in Section 9.6.1, this is known to be a problem with vitamin Be, because some 80% of the total body pool is associated with muscle glycogen phosphorylase and has a much lower fractional turnover rate than the remaining 20%. 

This is considerably lower than the requirements estimated from depletion/ repletion studies (Section 9.6.2) and may reflect dilution of the small pool associated with amino acid metaholism, which has a rapid turnover, by the larger and more stable pool associated with glycogen phosphorylase. 

This large, slow turnover pool is most likely in muscle, which contains about 70-80% of the vitamin B6 in the body (Cobum et al, 1985,1988b). The muscle pool is associated primarily with glycogen phosphorylase (Butler et al, 1985). Using pyridoxal phosphate as an indicator of glycogen phospho-... 

A third consequence is the question of whether glycogen phosphorylase conserves vitamin B6 because it has a very low rate of degradation or because it recycles the pyridoxal phosphate very efficiently. Based on the rapid decay of the free vitamin B6 pool in muscle, the slow turnover of the protein-bound vitamin B6 pool, the failure to detect apo-phosphorylase, and the agreement between turnover rates based on amino acid or vitamin B6 data, Beynon et al. (1986) concluded that recycling would be minimal. We feel that the effect of vitamin B6 intake on turnover rates tends to favor the recycling option under conditions of limited intake. However, more data are needed before a final decision can be made. 

Beynon, R. J., Fairhurst, D.. and Cookson, E. J. (1986). Turnover of skeletal muscle glycogen phosphorylase. Biomed. Biochim. Acta 45,1619-1625. 

Butler, P. E., Cookson, E. J., and Beynon, R. J. (1985). The turnover of skeletal musde glycogen phosphorylase studied using the cofactor, pyridoxal phosphate, as a specific label. Biochim. Biophys. AcU> 847, 316-323. 

FIG. 1. Interrelationships between vitamin B6 and phosphorylase metabolism. The low rate of turnover of glycogen phosphorylase (gpb) and the lack of exchange of free and protein-bound PLP mean that exchange into the muscle pool is largely controlled by the kinetics of turnover of the enzyme. At present, it is not known whether resolution of the holo-enzyme is a prerequisite or consequence of phosphorylase degradation. Reproduced with permission of llie Biochemical Journal. 

Beynon, R. J., leyland, D. M., Evershed, R. P., Edwards, R. H. T., and Cobum, S. P. (1996). Measurement of the turnover of glycogen phosphorylase by gas chromatography/mass spectrometry using stable isotope derivatives of pyridoxine (Vitamin B6). Biochem. J. 317, 613-619. 

The rate constant for turnover of the slow component was 0.13 0.03/ day (mean SEM., n = 10) from which a value of turnover of the phosphorylase pool can be calculated as 0.1/day (Beynon etal, 19%). This compares well with values of 0.12/day obtained for gastrocnemius muscle (Leyland et ai, 1990) and 0.13/day for total hind limb and back muscle (Leyland and Beynon, ). The fast pool (presumed to be all labile forms of the vitamin) was turning over very quickly, with a rate constant of 1.3 0.4/day (a half-life of 12 hr). However, the experimental protocol that we use does not permit acquisition of a sufficiently detailed data set to acquire accurate kinetics on the fast pool. This preliminary analysis of the data also implies that the fast pool accounts for about 50% of the total vitamin B6 in the body—it is not yet clear whether this is consequential to the inability to define the fast phase with a high degree of precision or whether the muscle phosphorylase itself partitions into two pools that differ in accessibility. For example, enzyme bound to the glycogen particle might be more stable than enzyme free in the sarcoplasm. Further work is needed to resolve these issues. 

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