Disease relevance of Vitamin K hydroquinone

• The efficacy and toxicity of vitamin K depends on the pathway and the extent of enzymatic reductive activation to vitamin K hydroquinone, which is an essential cofactor for the synthesis of clotting factors [1].

High impact information on Vitamin K hydroquinone

• Because vitamin K is in excess in both the untransfected and vitamin K epoxide reductase (VKOR)-transfected cells, the simplest explanation for this result is that VKOR catalyzes both the reduction of vitamin K epoxide to vitamin K and the conversion of vitamin K to vitamin K hydroquinone [2].
• Although Cbx 676 had a normal carboxylase active site in terms of the Km for FLEEL and its stimulation by proPT18, the Km for vitamin K hydroquinone was 540 microM, and the specific epoxidase activity was 97 pmol KO/30 min/pmol of Cbx 676 [3].
• Mutagenesis of vitamin K-dependent carboxylase demonstrates a carboxyl terminus-mediated interaction with vitamin K hydroquinone [3].
• NAPQI, on the other hand, appeared to interfere with VKD carb activity via two mechanisms; 1) oxidation of the cofactor vitamin K-hydroquinone, 2) inactivation of the enzyme [4].
• Lipid peroxidation was inversely related to the amount of vitamin K hydroquinone in the reaction [5].

Biological context of Vitamin K hydroquinone

• This complex recycles vitamin K 2,3-epoxide to vitamin K hydroquinone, a cofactor that is essential for the post-translational gamma-carboxylation of several blood coagulation factors [6].

Anatomical context of Vitamin K hydroquinone

• It has been postulated that the liver microsomal conversion of vitamin K hydroquinone to its 2,3-epoxide (epoxidase activity) is coupled in some obligatory fashion to the vitamin K-dependent carboxylation (carboxylase activity) event also occurring in microsomes [7].

Gene context of Vitamin K hydroquinone

• As vitamin K hydroquinone is converted to vitamin K epoxide (VKO) in every carboxylation step, the epoxide has to be recycled to the reduced form by the vitamin K epoxide reductase complex (VKOR) [8].
• Based on the assumption that in vivo thioredoxin also plays a role in the regeneration of vitamin K hydroquinone from the epoxide, an extension of the generally accepted vitamin K cycle is proposed [9].
• Vitamin K hydroquinone formation in rat liver can be catalyzed by a thiol-dependent quinone reductase activity which shares several characteristics with the vitamin K 2,3-epoxide reductase activity [10].

Analytical, diagnostic and therapeutic context of Vitamin K hydroquinone

• Inhibition by spin-trapping agents suggests a free radical step in the vitamin K hydroquinone-dependent reaction, similar to other mixed function oxidations [11].

References