Vitamin B6 deficiency

There is evidence that some people are sensitive to free glutamates. These people get headaches or other symptoms if they ingest too much. This may be related to pyridoxine (vitamin B6) deficiencies, as this vitamin is necessary for glutamate metabolism. People with uncontrolled severe asthma may find that glutamates complicate or worsen their symptoms. 

The association between vitamin B6 deficiency and transamination emerged from 1945 when Schlenk and Fisher noted that pyridoxine-deficient rats had a diminished capacity for transamination. In the same year Gunsalus and his colleagues found transamination in Streptococcus faecalis depended on pydridoxal phosphate. The properties of the heat-stable component in purified glutamic-oxaloacetate transaminase were similar to those of pydridoxal phosphate. Later pyri-doxal phosphate was established as an essential coenzyme in many amino acid transformations. 

The amount of vitamin B6 required by humans is not well established,73 and only recently has evidence been obtained that the needs are variable. Hansen and Bessey74 have found that in some babies 3 or 4 times as much vitamin B6 is needed to prevent the excretion of xanthurenic acid after a test dose of tryptophane than in others. It is these particular babies who develop clinical vitamin B6 deficiency when the intake is low. These findings seem to indicate strongly that some babies have vitamin B6 requirements 3 or 4 times as high as others. 

Gershoff, S. N., and Earagalla, E. F. (1959). Endogenous oxalate synthesis and glycine, serine, deoxypyridoxine interrelationships in vitamin B6-deficient rats. /. Biol. Chem. 234, 2391-2393. 

Like folate and vitamin C, vitamin B6 (pyroxidine) is water soluble and like folate has several vitamers. Vitamin B6 may be involved in more bodily functions than any other nutrient (Tambasco-Studart et al., 2005), is a cofactor for many enzymes, especially those involved in protein metabolism, and is also a cofactor for folate metabolism. Vitamin B6 has anticancer activity (Theodoratou et al., 2008), is a strong antioxidant (Denslow et al., 2005), is involved in hemoglobin biosynthesis, lipid and glucose metabolism and immune and nervous system function. Possible consequences of deficiency include anemia, impaired immune function, depression, confusion, and dermatitis (Spinneker et al., 2007). Vitamin B6 deficiency is generally not a problem in the developed world, but there could be as yet poorly defined consequences of suboptimal intake particularly for the elderly. 

Isonicotinyl hydrazide (INH), one of the most effective drugs against tuberculosis, is inhibitory to pyridoxal kinase, the enzyme that converts pyridoxal to PLP.C Apparently, the drug reacts with pyridoxal to form a hydrazone which blocks the enzyme. Pyridoxal kinase is not the primary target of INH in mycobacteria. However, patients on long-term isonicotinyl hydrazide therapy sometimes suffer symptoms of vitamin B6 deficiency. ... 

Kratzer (1946) reported that pyridoxine supplementation in chicks on diets containing a linseed meal was necessary to counteract the vitamin B6 deficiency. Klosterman et al. (1967) identified the antipyridoxine factor linatine. Although linatine is a problem in chicks, flaxseed has not been associated with a vitamin B6 deficiency in humans. In fact, no affect on serum pyridoxine levels in subjects consuming 45 grams of flaxseed per day over 5 weeks was observed (Dieken, 1992). 

On supplementing SeMet, GSH-Px activities reach a maximum value and then plateau, while tissue Se levels continue to rise in proportion to the dosage (Deagen et al, 1987). The release of Se from SeMet also depends on vitamin B6 status. In rats maintained on a feed supplemented with 0.25 mg Se/kg of diet in the form of SeMet, GSH-Px activities in erythrocytes, muscle and heart were lower in vitamin B6-deficient than in vitamin B6-supplemented animals (Yin et al, 1996). Vitamin B6 also significantly reduced lipid peroxide contents in tissues. These results indicate that dietary vitamin B6 is involved in the metabolic breakdown of SeMet. 

The uptake and accumulation of various amino acids in Lactobacillus arabinosus have been described. Deficiencies of vitamin B6, biotin, and pantothenic acid markedly alter the operation of these transport systems. Accumulation capacity is decreased most severely by a vitamin B6 deficiency. This effect appears to arise indirectly from the synthesis of abnormal cell wall which renders the transport systems unusually sensitive to osmotic factors. Kinetic and osmotic experiments also exclude biotin and pantothenate from direct catalytic involvement in the transport process. Like vitamin B6, they affect uptake indirectly, probably through the metabolism of a structural cell component. The evidence presented supports a concept of pool formation in which free amino acids accumulate in the cell through the intervention of membrane-localized transport catalysts. 

Therefore, the three vitamin deficiencies so far studied in detail appear to affect amino acid transport and accumulation in similar but indirect ways. The accumulation defect is most pronounced in vitamin B6-deficient cells, for which there is also strong evidence implicating an abnormality in cell wall composition as a likely source of the change in transport activity. Direct evidence for a cell wall change in biotin- and pantothenate-deficient cells has not yet been obtained. The possibility remains, therefore, that the change in accumulation activity may be caused by an abnormality in some other structural component such as the peripheral cell membrane. 

Figure 7. Comparative stimulation of glutamic acid, alanine, and proline accumulation in vitamin B6-deficient cells of L. arabinosus at various extracellular sucrose concentrations...

Further support comes from the studies relating cell wall biosynthesis and amino acid accumulation capacity in vitamin B6-deficient cells, since it is difficult to account for these observations without attributing considerable osmotic activity to the accumulated amino acids. Any description of accumulation which invokes amino acid attachment to intracellular binding sites, whose affinity can be reduced by a vitamin B6 deficiency, must account for the stimulation of uptake that accompanies the synthesis of essentially extracellular cell wall material. If the reduction in affinity occurs because the cell interior becomes overhydrated (a reasonable postulate which follows from the osmotic experiments), the beneficial effect of wall synthesis is not readily explicable, since vitamin B6-deficient cells have a swollen appearance which is not significantly altered after wall synthesis has been stimulated. Thus, the existing overhydration within the cell probably is not reversed by this change. In contrast, the deposition of additional wall substance would prevent further unfavorable consequences of swelling such as membrane distention, and, in this way, forestall the premature cessation of amino acid accumulation. 

Tryptophan catabolism is also associated with several dead-end pathways, for example the formation of kynurenic and xanthurenic acids. Normal urine contains small amounts of hydroxykynurenine, kynurenine, kynurenic acid, and xanthurenic add. When large amounts of tryptophan are fed to animals, the excretion of these compounds increases. Xanthurenic acid is excreted in massive quantities in vitamin B6 deficiency. 

Antibiotics. Long-term administration of antibiotics could lead to vitamin B6 deficiency, If symptoms of peripheral neuropathy develop (numbness and tingling of the extremities), administer vitamin B6. Sulfasalazine can decrease the absorption of folic acid, and trimethoprim can cause folate deficiency, hence the need to administer folic acid if there is evidence of deficiency. Rifampicin can cause disturbances in vitamin D metabolism and lead to osteomalacia. The absorption of tetracyclines can be reduced by calcium, magnesium, iron and zinc, while this antibiotic could also decrease the absorption of these minerals. This effect is probably least with minocycline and is not confirmed with doxycycline. Doses of minerals and antibiotic should be separated by at least 2 hours. The absorption of quinolones is reduced by cationic and anionic supplements. 

The long-term intake of hydralazine could lead to vitamin B6 deficiency, while the therapeutic effects of verapamil could be antagonized by calcium supplements. 

Excess xanthurenate in the urine. Xanthure-nate levels in the urine increase with vitamin B6 deficiency because B (as pyridoxal phosphate) is necessary for the further chemical transformation of 3-hydroxykynurenine. Pyridoxine deficiency may be detected by giving the patient a loading dose of tryptophan. If pyridoxine deficiency is present, there will be a detectable excess of xanthurinate in the urine. Oral contraceptives may increase urinary xanthurenate levels, possibly... 

In healthy volunteers, theophylline reduced circulating pyridoxal phosphate (vitamin B6) concentrations, presumably by noncompetitive inhibition of pyridoxal kinase. Theophylline concentrations of approximately 10 gg/ml produced only partial inhibition, plasma pyridoxal kinase and pyridoxal concentrations being unaffected. The authors speculated that with theophylline overdose and greater inhibition, vitamin B6 deficiency might contribute to seizures (SEDA-14, 2). 

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