Function of Vitamin Bg

Vitamin Bg has a crucial role in 1-carbon metabolism, which involves DNA synthesis and DNA methylation, and can modulate gene expression. Electrochemical and spectroscopic studies (Liu et al. 2008) have shown that vitamin Bg can interact with DNA. These findings are helpful in understanding the biological functions of vitamin Bg. 

Vitamin Bs consists of six forms in nature, i.e. pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM), pyridoxine 5 -phosphate (PNP), pyridoxal 5 -phosphate (PLP), and pyridoxamine 5 -phosphate (PMP) (Figure 22.1). PLP is a coenzyme for many enzymes involved in amino acid and carbohydrate metabolism, and plays a key role in the nutritional function of vitamin Bg. The other forms show the same nutritional efficiency because they are converted into PLP in cells. The free forms of vitamin Bg are adsorbed through the intestinal mucosa, and then are phosphorylated and converted into PLP in the liver. Some PLP exits the liver and travels in the blood on albumin, being turned over slowly. PL is the form most actively transported to other cells from the liver. The cells adsorb PL and then phosphorylate it to yield PLP. The final metabolite derived from vitamin Bg is 4-pyridoxic acid (4-PA, Figure 22.1), which is excreted into the urine. Plants contain a storage form of vitamin Bg, pyridoxine-p-glucoside... 

Recent studies clarified novel functions of vitamin Bg forms. All forms are strong quenchers of singlet oxygen. Pyridoxamine reduces the incidence of diabetic complications. PLP prevents the progression of diabetic nephropathy. 

Deficiency of this coenzyme can lead to many manifestations. Clinical signs include retarded growth, acrodynia, alopecia, skeletal changes and anemia, while changes in neurotransmitters, such as dopamine, serotonin, norepinephrine (noradrenaline), tryptamine, tyramine, histamine, y-aminobutyric acid, and taurine, affect the brain function and can lead to seizures and convulsions. An overdose of vitamin Bg leads to neuronal damage and sensory and motor effects [417],... 

The metabolic significance of vitamin Bg and its role to the growth and functional development have been published (67-78). 

Morra M, Philipszoon HD, D Andrea G, et al. (1993) Sensory and motor neuropathy caused by excessive ingestion of vitamin Bg A case report. Functional Neurology 8(6) 429—432. 

A deficiency of vitamin Bg alone is uncommon, and it is more usual to expect the problem to occur in association with deficits in other vitamins of the B-complex. As with other water-soluble vitamins that function as coenzymes, the relative affinity of the coenzyme for a given apoenzyme and the extent to which a particular holoenzyme-catalyzed reaction is essential are reflected in the progressive symptomatology of deficiency of the vitamin. Investigations of the consequences of vitamin Bg deficiency in the human use... 

As with the other B vitamins that act as coenzymes biochemical assessment of vitamin Bg can, be made by direct chemical analysis of the vitamer or its metabolites, or by functional means. Measurements that have been used are PLP in plasma or red cells, its metabolite 4 PA in urine or plasma, the activity and activation coefficient of the red cell aminotransferases (aspartate and alanine), and the tryptophan load metabolite excretion test. As no single marker adequately reflects status, a combination of these markers olfers the best approach. 

Functional assessment of vitamin Bg status may be made by measuring the activity of red cell aspartate (or alanine) aminotransferase, and its activation coefficient on incubation with PLP, though as the apoenzyme is highly unsaturated with PLP, the results obtained have more variability than corresponding methods for vitamins Bi and B2 and are thus considered less useful. Activation coefficients of less than about 1.5 for aspartate aminotransferase and 1.2 for... 

The phosphorylated and non-phosphorylated forms of vitamin Bg have various physical and chemical properties. Vitamin Bs in the form of pyridoxal-5 -phosphate (PLP) and to a lesser extent, pyridoxamine-5 -phosphate (PMP), functions as a coenzyme in over 100 enzymatic reactions. All the forms of vitamin Be possess vitamin activity because they can be converted in vivo to pyridoxal. PN, PM and PL are converted to 5 -phosphate by a single kinase enzyme which in the brain and liver is most active with zinc. PNP and PMP are then converted to PLP by flavin dependent oxidase this is the reason why vitamin B2 deficiency causes a fall in available PLP (Holman 1995). Human cells can synthesize PLP from three vitamers via the Bg salvage pathway but cannot synthesize PLP de novo and must obtain it from dietary sources. 

The chemistry of pyridoxal and some of its phosphorylated derivatives has been the subject of continuous research directed toward the elucidation of the relationship between structure and biological activity. A variety of different derivatives of vitamin Bg have been described. For many of them the precise function is not understood, yet these derivatives have novel functions and could be crucial to fully understanding the biological relevance of vitamin Bg. 

A small number of papers on the determination of vitamins Bg and B12 in fortified food using ED techniques have been published. A wide variety of compounds is capable of being monitored with a coulometric detector. In general, electroactivity is dependent on presence of functional group of molecules (Flanagan et al. 2005 Trojanowicz 2011). 

This chapter focuses on the function and effects of vitamin Bg, particularly its potentially protective effect against chronic diseases. 

The level of steroid-induced gene expression from simple promoters containing only hormone response elements and a TATA sequence was not affected by changes in the vitamin Bg status. However, the modulatory influence of vitamin Bg status was restored when a binding site for a transcription factor, nuclear factor (NFI), was included within the hormone-responsive promoter, indicating that PLP modulates gene expression through its influence on a functional interaction between the steroid hormone receptors and transcription factor NFI (71). 

M.K. Baum, E. Mantero-Atienze, G. Shor-Posner, M.A. Fletcher, R. Morgan, C. Eisdorfer, H.E. Sauberlich, P.E. Cornwall, and R.S. Beach. Association of vitamin Bg status with parameters of immune function in early HIV-1 infection. J. Acqui. Immune Defic. Syndr. 4 1122-1132 (1991). 

The crucial role played by vitamin Bg in the nervous system and in neuroendocrinology is based on the fact that various putative neurotransmitters as well as taurine, sphingolipids, and polyamines are synthesized by pyridoxal phosphate (PLP)-dependent enzymes. There are numerous biological effects of vitamin Bg unrelated to the role of PLP as a coenzyme. PLP is an antagonist of both the voltage-mediated and the ATP-mediated calcium transport systems. PLP modulates the activities of steroid hormone receptors and transcription factors. The preventive effect of vitamin Bg on tumorigenesis might also derive from the antioxidant functions of this vitamin. 

Many of the biochemical reactions of amino acids require pyridoxal 5 -phosphate (PLP), the active form of vitamin Bg, as a coenzyme. Before acting on an amino acid, PLP uses its aldehyde function to form an imine with the amino group of a lysine side chain of a protein. 

For the first time, such an approach was used by Metzler and collaborators [20] who studied the two-component tautomeric equilibrium between the neutral form (37b, Chapter 1) and the dipolar ion (37a, Chapter 1) of 3-hydroxypyridine in water and water/methanol binary mixtures at various temperatures. Very similar is the procedure used by Reeves et al. [21] for the analysis of the keto-enol tautomerism of 4-phenylazo-l-naphthol-2,4 -disulfonate VSzquez Segura and collaborators [22] in the case of 5 -deoxypyridoxal and Vilanova et al. [23] for the analysis of tautomeric members of vitamin Bg family. In all these cases, the individual bands belonging to tautomers are mathematically resolved using a suitable band-shape function (in this case log-normal [18]), and the corresponding spectral areas I are calculated. The tautomeric constant Kj. is then given as... 

Allenic amino acid derivatives 50, which are of special interest as selective vitamin Bg decarboxylase inhibitors [35], are accessible through 1,6-cuprate addition to 2-amino-substituted enynes 49 (Eq. 4.22) [36]. Because of the low reactivity of these Michael acceptors, however, the reaction succeeds only with the most reactive cuprate the t-butyl cyano-Gilman reagent tBu2CuLi-LiCN. Nevertheless, the addition products are obtained with good chemical yields, and selective deprotection of either the ester or the amino functionality under acidic conditions provides the desired target molecules. 

After decontamination by emesis or lavage, patients should be carefully monitored for alterations in liver and kidney function, and treated symptomatically if necesseray. Seizures can be treated with anti-convulsant drugs. Because the toxin produces a deficiency of y-amino-butyric acid (GABA), specific treatment with pyridoxine (vitamin Bg) has been recommended. 

Vitamin Bg is a mixture of six interrelated forms pyridoxine (or pyridoxol) (Figure 19.23), pyri-doxal, pyridoxamine, and their 5 -phosphates derivatives. Interconversion is possible between all forms. The active form of the vitamin is pyridoxal phosphate, which is a coenzyme correlated with the function of more than 60 enzymes involved in transamination, deamination, decarboxylation, or desulfuration reactions. 

Water-soluble vitamins. Water-soluble vitamins include vitamin C, and those of the B-complex group biotin, folate, niacin, pantothenic acid, riboflavin, thiamine, vitamin Bg and vitamin B12. They function mainly as coenzymes and prosthetic groups. 

The tryptophan load test for vitamin Bg nutritional status (the ability to metabolize a test dose of tryptophan) is one of the oldest metabolic tests for functional vitamin nutritional status. It was developed as a result of observation of the excretion of an abnormal-colored compound, later identified as the tryptophan metabolite xanthurenic acid. 

In addition to its functions in bone, energy transfer, and nucleic acids, phosphate serves to prevent the leakage of biochemicals from the cell. The phosphate groups of nucleotides, intermediates of glycolysis, and vitamin Bg greatly impair the... 

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