Search

Phylloquinone (vitamin [K.sub.1]) is a bipartite molecule that consists of a naphthoquinone ring attached to a phytyl side chain. The coupling of these 2 moieties depends on the hydrolysis of the CoA thioester of 1,4-dihydroxy-2-naphthoate (DHNA), which forms the naphthalenoid backbone. It is not known whether such a hydrolysis is enzymatic or chemical. In this study, comparative genomic analyses identified orthologous genes of unknown function that in most species of cyanobacteria cluster with predicted phylloquinone biosynthetic genes. The encoded approximately 16-kDa proteins display homology with some Hotdog domain-containing CoA thioesterases that are involved in the catabolism of 4-hydroxybenzoyl-CoA and gentisyl-CoA (2,5-dihydroxybenzoyl-CoA) in certain soil-dwelling bacteria. The Synechocystis ortholog, encoded by gene sir0204, was expressed as a recombinant protein and was found to form DHNA as reaction product. Unlike its homologs in the Hotdog domain family, Sir0204 showed strict substrate specificity. The Synechocystis sir0204 knockout was devoid of DHNA-CoA thioesterease activity and accumulated DHNA-CoA. As a result, knockout cells contained 13-fold less phylloquinone than their wild-type counterparts and displayed the typical photosensitivity to high light associated to phylloquinone deficiency in cyanobacteria. cyanobacteria | isoprenoids | photosynthesis | phylloquinone

Objectives: To measure uptake and disposal kinetics and absolute absorption of vitamin K, using two stable isotope-labelled forms of vitamin [K.sub.1]. Subjects: Ten subjects (nine women and one man) aged between 22 and 31 years, with a mean ([+ or -] standard deviation) body mass index of 22.5 [+ or -] 2.4 kg/[m.sup.2]. Subjects took capsules containing 3 [micro]g of methyl-[sup.13]C vitamin [K.sub.1], three times a day for six days to reach a steady state for plasma vitamin [K.sub.1]. isotopic enrichment. On day seven, subjects were given an intravenous dose of Konakion MM to measure disposal kinetics and at the same time, a capsule containing 4 [micro]g of ring-[D.sub.4] vitamin [K.sub.1] to measure absorption. Plasma vitamin [K.sub.1] concentration was measured by high-performance liquid chromatography and isotopic composition by gas chromatography mass spectrometry. Results: The disposal kinetics of the intravenous dose of vitamin [K.sub.1] were resolved into two exponentials with half-times of 0.22 ([+ or -] 0.14) and 2.66 ([+ or -] 1.69) h. Absorption of oral, deuterated vitamin [K.sub.1] was 13 ([+ or -] 9) %. Conclusions: Two-compartmental kinetic parameters observed in this study are similar to those obtained previously using radioactive tracers, but there may be additional slow-turnover body pools acting as stores of vitamin [K.sub.1]. The kinetic parameters determined from the intravenous dose allowed determination of the absolute absorption of vitamin [K.sub.1] from a bolus oral dose. doi:10.1038/sj.ejcn.1602859; published online 1 August 2007 Keywords: vitamin [K.sub.1]; phylloquinone; stable isotope; kinetics; absorption, Introduction Vitamin K is a fat-soluble vitamin required as a cofactor in the post-translational carboxylation of glutamic acid to [gamma]-carboxyglutamic acid in vitamin K-dependent (VKD) proteins. VKD proteins were originally [...]