Chemistry of vitamin B6 under oxidative stress

• Vitamin B6, or pyridoxine, is the precursor of the biologically active derivatives pyridoxal-5’-phosphate and pyridoxamine-5’-phosphate (Fig.1), with functional roles in a number of different enzymes. Pyridoxine itself is a cofactor of several enzymes that catalyze decarboxylations, transaminations, and racemations of amino acids. Bacteria, fungi, and plants produce their own vitamin B6, whereas parasitic organisms and higher animals have to acquire vitamin B6 through nutrient intake.Lately, pyridoxine biosynthesis-deficient mutants of fungi and yeast have been shown to be sensitive to reactive oxygen species (ROS) such as singlet oxygen and hydrogen peroxide. This suggests that vitamin B6 and its derivatives are also involved in stress tolerance in living organisms, especially in alleviating oxidative stress. In eukaryotes, stress resistance has been implied to involve pyridoxine-dependent singlet oxygen quenching, whereby the pyridoxine itself would react with and quench the singlet oxygen. The oxidative stress-protective effect of pyridoxine has also been described both in red blood cells and in lens cells in animals. Pyridoxine itself was found to be the most effective of the vitamin B6 species, twice as effective as pyridoxal-5’-phosphate, and as effective as vitamin E. Knowledge about this novel mechanism of reaction between pyridoxine or its derivatives (cf. Figure 1) and singlet oxygen and other ROS is however very limited. However, since both the aldehyde (pyridoxal) and the amino (pyridoxamine) derivatives only to a small extent influence the rate of reaction, these moieties are probably not involved. Also, since the heteroaromatic absorbance peak at 323 nm disappears during the reaction, at least one of the targets for singlet oxygen is most likely the core of the aromatic ring, leading to ring opening.In order to shed more light on the possible role of pyridoxine in stress tolerance / protection we herein report on computational studies of possible reaction mechanisms between pyridoxine and different ROS (singlet oxygen, superoxide and hydrogen peroxide) by means of density functional theory (DFT) based methods. It is concluded that the compound has an extremely high quenching power towards hydroxyl radicals. We furthermore explore the explicit UV-induced photolysis pathways of the compound, as well as enzymatic degradation (ring-opening) by bacterial flavoprotein monooxygenases.

Subject headings

NATURVETENSKAP  -- Biologi -- Botanik (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Botany (hsv//eng)

Keyword

Biochemistry

Biokemi

Publication and Content Type

ref (subject category)

kon (subject category)