Carboxylative efficacy of trans and cis MK7 and comparison with other vitamin K isomers

AbstractCarboxylative enzymes are involved in many pathways and their regulation plays a crucial role in many of these pathways. In particular, γ-glutamylcarboxylase (GGCX) converts glutamate residues (Glu) into γ-carboxyglutamate (Gla) of the vitamin K-dependent proteins (VKDPs) activating them. VKDPs include at least 17 proteins involved in processes such as blood coagulation, blood vessels calcification, and bone mineralization. VKDPs are activated by the reduced form of vitamin K, naturally occurring as vitamin K1 (phylloquinone) and K2 (menaquinones, MKs). Among these, MK7 is the most efficient in terms of bioavailability and biological effect. Similarly to othertrans isomers, it is produced by natural fermentation or chemically in bothtrans andcis. However, the efficacy of the biological effect of the different isomers and the impact on humans are unknown. Our study assessed carboxylative efficacy oftrans andcis MK7 and compared it with other vitamin K isomers, evaluating both the expression of residues of carboxylated Gla-protein by western blot analysis and using a cell-free system to determine the GGCX activity by HPLC.Trans MK7H2 showed a higher ability to carboxylate the 70  KDa GLA-protein, previously inhibited in vitro by warfarin treatment. However,cis MK7 also induced a carboxylation activity albeit of a small extent. The data were confirmed chromatographically, in which a slight carboxylative activity ofcis MK7H2 was demonstrated, comparable with both K1H2...
Source: BioFactors - Category: Biochemistry Authors: Tags: Research Communication Source Type: research