Abstract
The aim of the study was to evaluate the plasma levels of vitamin K (VK), prothrombin, des-γ-carboxyprothrombin (DCP) by ELISA with two types of monoclonal antibodies (MU-3 and 19B7), and urinary γ-carboxyglutamic acid (γ-Gla) in healthy adults (45 males and 45 females) and 11 patients with liver cirrhosis. VK and γ-Gla were analyzed by reverse-phase HPLC, prothrombin was determined using a method with a synthetic chromogenic substrate, and DCPs were analyzed by immunoaffinity chromatography and reverse-phase HPLC, and measured by ELISA. We were able to detect phylloquinone K (PK) and menaquinones MK-4, -5, -6, -7, -8 and -9, and we isolated several DCPs from plasma. Age had significant positive correlations with levels of urinary γ-Gla, plasma MK-7 and total VK, and VKDPs (prothrombin and DCP using MU-3 antibody) in the healthy adults. Significant positive correlations were also found between urinary γ-Gla and plasma levels of PK, MK-4, MK-7, and total VK and VKDPs (prothrombin and DCP using MU-3 antibody) in the healthy adults. γ-Gla and total VK levels were significantly higher in healthy adults than in patients with liver cirrhosis, and VK components, prothrombin, DCPs, and the MU-3/19B7 ratio showed a tendency to be higher in the healthy adults. We conclude that the status of VK and related proteins may reflect the latent increase in des-γ-carboxylation in healthy aging.
Highlights
Vitamin K (VK) has two main forms, phylloquinone K (PK; VK1) and menaquinones (MK, VK2), and is increasingly understood to have important biological roles
Since γ-carboxyglutamic acid (γ-Gla) in a Gla-containing protein is stoichiometrically excreted into urine as free Gla, urinary Gla excretion is believed to reflect the rate of synthesis and degradation of vitamin K-dependent proteins (VKDPs) and utilization of VK in vivo
The correlation coefficients of the total amount of MK-5, -6, -8 and -9 were -0.123 with age and -0.08 with γ-Gla. These values were not significant, but may show a tendency for a decrease with age. These results show that VK increases with age in healthy adults, which suggests that VK is required for normal physiological aging
Summary
Vitamin K (VK) has two main forms, phylloquinone K (PK; VK1) and menaquinones (MK, VK2), and is increasingly understood to have important biological roles. MKs contain an unsaturated aliphatic side chain with a variable number of prenyl units; MKs are divided into short-chain (MK-4) and long chain (MK-5 to -13) subtypes. Both PK and MKs are cofactors for γ-glutamylcarboxylase, which catalyzes posttranslational conversion of specific glutamyl residues to γ-carboxyglutamyl residues in vitamin K-dependent proteins (VKDPs) involved in blood coagulation, bone and cartilage metabolism, signal transduction, and cell proliferation. VK serves as a cofactor for γ-glutamylcarboxylase, which catalyzes conversion of a Glu residue of VKDPs into γcarboxyglutamic acid (Gla). This process is driven by oxidation of VKH2 (hydroquinone) to VKO (epoxide) in the VK cycle. Since γ-Gla in a Gla-containing protein is stoichiometrically excreted into urine as free Gla, urinary Gla excretion is believed to reflect the rate of synthesis and degradation of VKDPs and utilization of VK in vivo
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