Pyridoxine oxidase

In addition to the role of flavoproteins in iron metabolism, it is possible that the anemia associated with riboflavin deficiency is a consequence of the impairment of vitamin Be metabolism in riboflavin deficiency. Pyridoxine oxidase is a flavoprotein and, like glutathione reductase, is very sensitive to riboflavin depletion (McCormick, 1989). Vitamin Be deficiency can result in hypochromic anemia as a result of impaired porphyrin synthesis. Although riboflavin depletion decreases the oxidation of dietary vitamin Be to pyridoxal (Section 9.2), it is not clear to what extent there is secondary vitamin Be deficiency in riboflavin deficiency This is partly because vitamin Be nutritional status is commonly... 

Like glutathione reductase, pyridoxine oxidase is sensitive to riboflavin depletion. In normal subjects and in experimental animals, the EGR and pyridoxine oxidase activation coefficients are correlated, and both reflect riboflavin nutritional status. In subjects with glucose 6-phosphate dehydrogenase deficiency, there is an apparent protection of EGR, so that even in riboflavin deficiency it does not lose its cofactor, and the EGR activation coefficient remains within the normal range. The mechanism of this protection is unknown. In such subjects, the erythrocyte pyridoxine oxidase activation coefficient gives a response that mirrors riboflavin nutritional status (Clements and Anderson, 1980). 

Figure 9.1. Interconversion of the vitamin Be vitamers. Pyridoxal kinase, EC 2.7.1.38 pyridoxine oxidase, EC 1.1.1.65 pyridoxamine phosphate oxidase, EC 1.4.3.5 and pyridoxal oxidase, EC 1.1.3.12. Relative molecular masses (Mr) pyridoxine, 168.3 (hydrochloride, 205.6) pyridoxal, 167.2 pyridoxamine, 168.3 (dihydrochloride, 241.1) pyridoxal phosphate, 247.1 pyridoxamine phosphate, 248.2 and 4-pyridoxlc acid, 183.2.

Metabolism of pyridoxine-related compounds in mammals. Enzymes 1, pyridoxal kinase (present in all mammalian tissues) 2, nonspecific (probably alkaline) phosphatases 3, pyridoxine oxidase (cofactor is FMN O2 is required subject to product inhibition) 4, aldehyde oxidase or aldehyde dehydrogenase 5, aminotransferase,... 

Levodopa interacts with many different drugs. When levodopa is used with phenytoin, reserpine, and papaverine, there is a decrease in response to levodopa The risk of a hypertensive crisis increases when levodopa is used with the monoamine oxidase inhibitors (see Chap. 31). Foods high in pyridoxine (vitamin B6) or vitamin B6 preparations reverse the effect of levodopa However, when carbidopa is used with levodopa, pyridoxine has no effect on the action of levodopa hi fact, when levodopa and carbidopa are given together, pyridoxine may be prescribed to decrease the adverse effects associated with levodopa... 

Pharmacologic doses of pyridoxine (vitamin B6 ) enhance the extracerebral metabolism of levodopa and may therefore prevent its therapeutic effect unless a peripheral decarboxylase inhibitor is also taken. Levodopa should not be given to patients taking monoamine oxidase A inhibitors or within 2 weeks of their discontinuance because such a combination can lead to hypertensive crises. 

Interactions The vitamin pyridoxine (B6) increases the peripheral breakdown of levodopa and diminishes its effectiveness (Figure 8.6). Concomitant administration of levodopa and monoamine oxidase (MAO) inhibitors, such as phenelzine (see p. 124), can produce a hypertensive crisis caused by enhanced catecholamine production therefore, caution is required when they are used simultaneously. In many psychotic patients, levodopa exacerbates symptoms, possibly through the buildup of central amines. In patients with glaucoma, the drug can cause an increase in intraocular pressure. Cardiac patients should be carefully monitored because of the possible development of cardiac arrhythmias. Antipsychotic drugs are contraindicated in parkinsonian patients, since these block dopamine receptors and produce a parkinsonian syndrome themselves. 

It has been suggested that there may be some benefit of using tryptophan in selected patients, particularly those with psychomotor retardation (3). Unfortunately, most of these reports have appeared as letters to the editors of journals (4-6) or as preliminary communications (7). In addition to the possible absence of any consistent effect, there are many plausible reasons to explain the variability in response. Tryptophan has been given in both the racemic and monomeric (levorotatory) forms, both alone and together with a number of substances intended to increase the synthesis or availability of serotonin, including monoamine oxidase (MAO) inhibitors (8), potassium or carbohydrate supplements (9), and co-enzymes such as pyridoxine or ascorbic acid (10). It has also been... 

Three enzymes play an active role in the metabolism of vitamin B6 in human erythrocytes. Pyridoxal kinase uses ATP to phosphorylate pyridoxine, pyri-doxamine, and pyridoxal. Pyridoxamine oxidase oxidizes pyridoxamine-5 -phosphate and pyridoxine-5 -phosphate to pyridoxal-5 -phosphate. The phosphatase activity produces pyridoxal from pyridoxal-5 -phosphate. The assay of the three enzymes required separation of the semicarbazone derivatives of pyridoxal-5 -phosphate and pyridoxal. The mobile phase used by Ubbink and Schnell (1988) contained 2.5% acetonitrile. Detection was by fluorescence. 

The phosphorylated vitamers are dephosphorylated by membrane-bound alkaline phosphatase in the intestinal mucosa pyridoxal, pyridoxamine, and pyridoxine are all absorbed rapidly by carrier-mediated diffusion. Intestinal mucosal cells have pyridoxine kinase and pyridoxine phosphate oxidase (see Figure 9.1), so that there is net accumulation of pyridoxal phosphate by metabolic trapping. Much of the ingested pyridoxine is released into the portal circulation as pyridoxal, after dephosphorylation at the serosal surface. 

Tissue uptake of vitamin Be is again by carrier-mediated diffusion of pyridoxal (and other unphosphorylated vitamers), followed by metabolic trapping by phosphorylation. Circulating pyridoxal and pyridoxamine phosphates are hydrolyzed by extracellular alkaline phosphatase. All tissues have pyridoxine kinase activity, but pyridoxine phosphate oxidase is found mainly in the liver, kidney, and brain. 

Pyridoxine phosphate oxidase is a flavoprotein, and activation of the erythrocyte apoenzyme by riboflavin 5 -phosphate in vitro can be used as an index of riboflavin nutritional status (Section 7.4.3). However, even in riboflavin deficiency, there is sufficient residual activity of pyridoxine phosphate oxidase to permit normal metabolism ofvitamin Be (Lakshmi and Bamji, 1974). Pyridoxine phosphate oxidase is inhibited by its product, pyridoxal phosphate, which binds a specific lysine residue in tbe enzyme. In tbe brain, tbe Ki of pyridoxal phosphate is of the order of 2 /xmol per L - the same as the brain concentration of free and loosely bound pyridoxal phosphate, suggesting that this inhibition may be a physiologically important mechanism in the control of tissue pyridoxal phosphate (Choi et al., 1987). 

Choi SY, Churchich ]E, Zaiden E, and Kwok F (1987) Brain pyridoxine-5-phosphate oxidase. Modulation of its catalytic activity by reaction with pyridoxal 5-phosphate and anedogs. Journal of Biological Chemistry 262,12013-17. 

Clements ]E and Anderson BB (1980) Glntathione reductase activity and pyridoxine (pyridoxamine) phosphate oxidase activity in the red cell. Biochimica etBiophysica Acta 632,159-63. 

Gregory JF 3rd (1980a) Effects of epsilon-pyridoxyllysine and related compounds onliver and brain pyridoxal kinase and liver pyridoxamine (pyridoxine) 5 -phosphate oxidase. Journal of Biological Chemistry 255, 2355-9. 

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