Pyridoxine Phosphorylase

Be Pyridoxine, pyridoxal, pyridoxamine Coenzyme in transamination and decarboxylation of amino acids and glycogen phosphorylase role in steroid hormone action Disorders of amino acid metabolism, convulsions... 

Six compounds have vitamin Bg activity (Figure 45-12) pyridoxine, pyridoxal, pyridoxamine, and their b -phosphates. The active coenzyme is pyridoxal 5 -phos-phate. Approximately 80% of the body s total vitamin Bg is present as pyridoxal phosphate in muscle, mostly associated with glycogen phosphorylase. This is not available in Bg deficiency but is released in starvation, when glycogen reserves become depleted, and is then available, especially in liver and kidney, to meet increased requirement for gluconeogenesis from amino acids. 

Pantothenic acid is present in coenzyme A and acyl carrier protein, which act as carriers for acyl groups in metabolic reactions. Pyridoxine, as pyridoxal phosphate, is the coenzyme for several enzymes of amino acid metabolism, including the aminotransferases, and of glycogen phosphorylase. Biotin is the coenzyme for several carboxylase enzymes. 

Pyridoxine is present in food in the free form and as a glucoside, which may undergo partial hydrolysis in the gut lumen, or may be absorbed intact. Although pyridoxine is associated with the enzyme glycogen phosphorylase in muscles, it is not released in response to a dietary deficiency therefore it cannot be regarded as a storage form of the vitamin. 

All aminotransferases have the same prosthetic group and the same reaction mechanism. The prosthetic group is pyridoxal phosphate (PLP), the coenzyme form of pyridoxine, or vitamin B6. We encountered pyridoxal phosphate in Chapter 15, as a coenzyme in the glycogen phosphorylase reaction, but its role in that reaction is not representative of its usual coenzyme function. Its primary role in cells is in the metabolism of molecules with amino groups. 

Factors which tend to decrease bioavailability of pyridoxine include (1) Administration of isoniazid (2) loss in cooking (estimated at 30-45%)—vitamin is water-soluble, (3) diuresis and gastrointestinal diseases (4) irradiation. Availability can be increased by stimulating intestinal bacterial production (very small amount), and storage in liver. The target tissues of Be are nervous tissue, liver, lymph nodes, and muscle tissue. Storage is by muscle phosphorylase (skeletal muscle—small amount). It is estimated that 57% of the vitamin ingested per day is excreted. The vitamin exerts only limited toxicity for humans. 

A second clue to the catalytic mechanism of phosphorylase is its requirement for pyridoxal phosphate (PLP), a derivative of pyridoxine (vitamin B5, Section 8.6.1). The aldehyde group of this coenzyme forms a Schiff base with a specific lysine side chain of the enzyme (Figure 21.7). The results of structural studies indicate that the reacting... 

With the exception of glycogen phosphorylase (Chapter 15), and kynureninase, all of the pyridoxine-requiring... 

Phosphorylase has a relatively low rate of turnover, and as such, large doses of radiolabeled pyridoxine were needed to obtain an adequate degree of labeling. In addition, the need for serial sampling of the decay curve, using individual animals, introduced substantial biological variation. Both aspects of this experimental system precluded application of the method to humans, and we considered the possibility of a different approach, based on stable-isotope-labeled pyridoxine, to monitor phosphorylase degradation. 

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. 

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