vitamin-k-1 and 1-4-naphthoquinone

Vitamin K is the common name for a group of compounds recognized as essential for blood clotting. The group comprises phylloquinone (K1)-a 2-methyl-3-phytyl-1,4-naphthoquinone; menaquinone (K2, MK)-a group of compounds with an unsaturated side chain in position 3 of a different number of isoprene units and a 1,4-naphthoquinone group and menadione (K3, MD)-a group of synthetic, water-soluble compounds 2-methyl-1,4-naphthoquinone. However, recent epidemiological studies suggest that vitamin K has various benefits that go beyond blood coagulation processes. A dietary intake of K1 is inversely associated with the risk of pancreatic cancer, K2 has the potential to induce a differentiation in leukemia cells or apoptosis of various types of cancer cells, and K3 has a documented anti-cancer effect. A healthy diet rich in fruit and vegetables ensures an optimal supply of K1 and K2, though consumers often prefer supplements. Interestingly, the synthetic form of vitamin K-menadione-appears in the cell during the metabolism of phylloquinone and is a precursor of MK-4, a form of vitamin K2 inaccessible in food. With this in mind, the purpose of this review is to emphasize the importance of vitamin K as a micronutrient, which not only has a beneficial effect on blood clotting and the skeleton, but also reduces the risk of cancer and other pro-inflammatory diseases. A proper diet should be a basic and common preventive procedure, resulting in a healthier society and reduced burden on healthcare systems.

Topics: DNA Damage; Humans; Micronutrients; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K 3; Water

In the last decades, a series of compounds, including quinones and polyphenols, has been described as having anti-fibrillogenic action on α-synuclein (α-syn) whose aggregation is associated to the pathogenesis of Parkinson's disease (PD). Most of these molecules act as promiscuous anti-amyloidogenic agents, interacting with the diverse amyloidogenic proteins (mostly unfolded) through non-specific hydrophobic interactions. Herein we investigated the effect of the vitamins K (phylloquinone, menaquinone and menadione), which are 1,4-naphthoquinone (1,4-NQ) derivatives, on α-syn aggregation, comparing them with other anti-fibrillogenic molecules such as quinones, polyphenols and lipophilic vitamins. Vitamins K delayed α-syn fibrillization in substoichiometric concentrations, leading to the formation of short, sheared fibrils and amorphous aggregates, which are less prone to produce leakage of synthetic vesicles. In seeding conditions, menadione and 1,4-NQ significantly inhibited fibrils elongation, which could be explained by their ability to destabilize preformed fibrils of α-syn. Bidimensional NMR experiments indicate that a specific site at the N-terminal α-syn (Gly31/Lys32) is involved in the interaction with vitamins K, which is corroborated by previous studies suggesting that Lys is a key residue in the interaction with quinones. Together, our data suggest that 1,4-NQ, recently showed up by our group as a potential scaffold for designing new monoamine oxidase inhibitors, is also capable to modulate α-syn fibrillization in vitro.

Topics: alpha-Synuclein; Antifibrinolytic Agents; Cell Nucleus; Humans; Magnetic Resonance Spectroscopy; Microscopy, Atomic Force; Naphthoquinones; Neurofibrils; Quinones; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamin K 3

Interruption of the phylloquinone (PhQ) biosynthetic pathway by interposon mutagenesis of the menA and menB genes in Synechocystis sp. PCC 6803 results in plastoquinone-9 (PQ-9) occupying the A(1) site and functioning in electron transfer from A(0) to the FeS clusters in photosystem (PS) I (Johnson, T. W., Shen, G., Zybailov, B., Kolling, D., Reategui, R., Beauparlant, S., Vassiliev, I. R., Bryant, D. A., Jones, A. D., Golbeck, J. H., and Chitnis, P. R. (2000) J. Biol. Chem. 275, 8523-8530. We report here the isolation of menB26, a strain of the menB mutant that grows in high light by virtue of a higher PS I to PS II ratio. PhQ can be reincorporated into the A(1) site of the menB26 mutant strain by supplementing the growth medium with authentic PhQ. The reincorporation of PhQ also occurs in cells that have been treated with protein synthesis inhibitors, consistent with a displacement of PQ-9 from the A(1) site by mass action. The doubling time of the menB26 mutant cells, but not the menA mutant cells, approaches the wild type when the growth medium is supplemented with naphthoquinone (NQ) derivatives such as 2-CO(2)H-1,4-NQ and 2-CH(3)-1,4-NQ. Since PhQ replaces PQ-9 in the supplemented menB26 mutant cells, but not in the menA mutant cells, the phytyl tail accompanies the incorporation of these quinones into the A(1) site. Studies with menB26 mutant cells and perdeuterated 2-CH(3)-1,4-NQ shows that phytylation occurs at position 3 of the NQ ring because the deuterated 2-methyl group remains intact. Therefore, the specificity of the phytyltransferase enzyme is selective with respect to the group present at ring positions 2 and 3. Supplementing the growth medium of menB26 mutant cells with 1,4-NQ also leads to its incorporation into the A(1) site, but typically without either the phytyl tail or the methyl group. These findings open the possibility of biologically incorporating novel quinones into the A(1) site by supplementing the growth medium of menB26 mutant cells.

Topics: Alkyl and Aryl Transferases; Chlorophyll; Cyanobacteria; Electron Spin Resonance Spectroscopy; Free Radicals; Genes, Bacterial; Light; Light-Harvesting Protein Complexes; Mutation; Naphthoquinones; Photosynthetic Reaction Center Complex Proteins; Photosystem I Protein Complex; Plastoquinone; Vitamin K 1; Vitamin K 3

Quinones play a vital role in the processes of electron transfer in bacterial photosynthetic reaction centers. It is of interest to investigate photochemical reactions involving quinones with a view to elucidate structure-function relationships in biological processes. Resonance Raman and FTIR spectra of electrochemically generated radical anions of 2-methyl-1,4-naphthoquinone, and 2-methyl-3-phytyl-1,4-naphthoquinone, also known as Vitamin K3 and Vitamin K1, respectively, (model compound for QA in Rhodopseudomonas viridis, a bacterial photosynthetic reaction center) have been reported. The same study has also been extended to 1,4-naphthoquinone for comparison. The vibrational assignments were carried out on the basis of comparison with our earlier time resolved resonance Raman studies on photochemically generated radical anions of 1,4-naphthoquinone and 2-methyl-1,4-naphthoquinone (Balakrishnan et al., J. Phys. Chem., 100, (1996), 16472-16478). These in vitro results have been compared with the reported vibrational spectral data under in vivo conditions.

Topics: Absorption; Anions; Models, Molecular; Naphthoquinones; Nuclear Magnetic Resonance, Biomolecular; Photosynthesis; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Vitamin K 1; Vitamin K 3

Topics: Animals; Fibrinolytic Agents; Metabolism; Mitochondria; Naphthoquinones; Oxidative Phosphorylation; Vitamin K; Vitamin K 1