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Osteoporosis
Published in Peter V. Giannoudis, Thomas A. Einhorn, Surgical and Medical Treatment of Osteoporosis, 2020
Ippokratis Pountos, Peter V. Giannoudis
Osteocalcin (OC) (Gla-protein, glutamic acid) is the most abundant noncollagenous protein of the extracellular bone matrix. Its exact role in the skeleton is obscure, even though it was described 40 years ago. It is a vitamin K–dependent protein that contains three γ-carboxyglutamic residues (12). OC is synthesized by osteoblasts, chondrocytes, and odontoblasts during the formation of extracellular bone matrix (12). It is largely incorporated in bone matrix; however, a small proportion (10%–30%) of the newly synthesized OC is released in the bloodstream (13). In addition to bone formation, it has been shown that small amounts of OC are also released during bone resorption. It is eliminated via the urine; hence, its levels can be artificially raised in patients with renal failure. Data from OC knockout models have shown that osteocalcin-deficient animals had a higher bone mass and bones with improved functional quality (14). In clinical studies, OC has been previously analyzed as a potential marker of bone formation, with findings showing a good correlation between the serum levels of osteocalcin and the level of bone formation but not resorption (15).
The Pathogenetic Role of Anti-Phospholipid Antibodies in Thrombosis
Published in E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson, Phospholipid-Binding Antibodies, 2020
R. H. W. M. Derksen, P. Hasselaar, Ph.G. de Groot
Protein C is a vitamin K-dependent protein, that after activation by thrombin, and in the presence of calcium ions and phospholipids exerts potent anticoagulant activity through rapid inactivation of factors V and VIII. Protein Ca inactivates both platelet-bound and free factor Va. Protein S, another vitamin K-dependent protein serves as a cofactor in protein Ca induced inactivation of factor Va49 (Figure 2).
Coagulation Theory, Principles, and Concepts
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Protein S is also a vitamin K-dependent protein. It circulates in plasma at about a concentration of 20 μg/mL as a single peptide chain having a molecular weight of 70,690. Protein S appears to form a 1:1 complex with activated protein C on lipid surfaces. Exactly how protein S accelerates the inactivation of factor Va and factor VIIIa is not known. Genetic deficiencies in protein S also cause a predisposition toward thromboembolic events.
Factor IX(a) inhibitors: an updated patent review (2003-present)
Published in Expert Opinion on Therapeutic Patents, 2022
Daniel K. Afosah, Edward Ofori, Madhusoodanan Mottamal, Rami A. Al-Horani
FIX is a vitamin K-dependent protein that is biosynthesized by hepatocytes as a precursor of a serine protease, FIXa [58]. It is biosynthesized as a precursor protein of 461 amino acids. During the biosynthesis, several posttranslational modifications take place resulting in a single chain of 415 residues and an average molecular weight of 57 kD [59]. Structurally, FIX possesses an N-terminal Gla domain (residues 1–40), a short hydrophobic stack (residues 41–46), two epidermal growth factor (EGF)-like domains (EGF1: residues 47–83, and EGF2: residues 88–127, that are linked by residues 84–87), an activation peptide (residues 146–180), and a C-terminal protease domain (residues 181–415) [60,61]. The Gla domain and EGF1 domain contain several binding sites for calcium ions. The zymogen FIX is activated to the enzyme FIXa by either the TF/FVIIa/calcium ion complex or FXIa/calcium ion [58], and that is by proteolytically cleaving the two peptide bonds at Arg145–Ala146 and Arg180–Val181, along with the release of a 35-residue activation peptide [59]. The resulting active protease i.e. FIXa contains a light chain (residues 1–145) and a heavy chain (residues 181–415) held together by a disulfide bond. The light chain consists of the Gla domain, EGF1 domain, and EGF2 domain, while the heavy chain contains the serine protease domain with the catalytic triad of Ser365 (chymotrypsin numbering 195), His221 (57), and Asp269 (102) [58]. The structure of FIXa is illustrated in Figure 4.
Clot activators and anticoagulant additives for blood collection. A critical review on behalf of COLABIOCLI WG-PRE-LATAM
Published in Critical Reviews in Clinical Laboratory Sciences, 2021
G. Lima-Oliveira, L. M. Brennan-Bourdon, B. Varela, M. E. Arredondo, E. Aranda, S. Flores, P. Ochoa
The endogenous anticoagulants are a varied group of proteins that act to limit or minimize coagulation either alone or in concert with each other [37]. In vivo, protein C, protein S, and antithrombin are the most important natural anticoagulants [38]. Protein C is a vitamin K-dependent protein synthesized predominantly in the liver as a single polypeptide chain that circulates as a zymogen; activated protein C inactivates F Va and F VIIIa [39,40] (Figure 2). Protein S, which is also vitamin K-dependent, is a non-enzymatic glycoprotein, a cofactor for activated protein C, that is synthesized by the endothelium and liver and then stored in endothelial cells and platelet alpha granules [41,42]. Protein S circulates in the plasma at a concentration of 350 nmol/L, 40% of which is free and 60%, bound to C4bBP; only the free form acts as a cofactor of protein C [43]. Protein S also has anticoagulant activity that is independent of activated protein C; in association with tissue factor pathway inhibitor, it inhibits F IXa [42,44], (Figure 2). Antithrombin is a serine protease inhibitor that influences the activity of several coagulation factors: F IIa, IXa, Xa, XIa, and XIIa [45–47] (Figure 2). Moreover, heparans, which are glycosaminoglycans expressed on endothelial cell surfaces and are formally known as endogenous heparin, are able to bind and activate antithrombin via allosteric activation [48,49].
Vitamin K status and inflammation are associated with cognition in older Irish adults
Published in Nutritional Neuroscience, 2020
A. Kiely, G. Ferland, B. Ouliass, P.W. O’Toole, H. Purtill, E.M. O’Connor
Vitamin K is generally known for its role in blood coagulation and is the general term for a group of fat-soluble compounds.1 However in recent years, a number of potential health benefits beyond coagulation have been attributed to vitamin K. While green leafy vegetables provide phylloquinone (or vitamin K1), the most widely consumed dietary form of the vitamin,2 high levels of a menaquinone (vitamin K2) isoform called menaquinone-4 (MK-4) have been reported in brain tissues.3 At the biochemical level, vitamin K is implicated in the production of sphingolipids, a group of lipids that comprise the myelin sheath of neuronal tissue3,4 and that are now recognised as important bioactive mediators of cell interaction, proliferation, senescence, differentiation and transformation.5 The vitamin K-dependent protein (VKDP) Growth-arrest specific gene-6 (Gas6) is present in the brain where it performs cell regulatory and myelination functions. A role for vitamin K in memory consolidation has also been documented. Carrie and colleagues (2011) conducted a feeding study on female Sprague–Dawley rats fed a low, adequate and high phylloquinone diet to determine the effects on spatial memory (using the Morris water maze test). Animals exposed to a high or adequate phylloquinone diet required less visual assistance to complete the task than rats on the vitamin K depleted diet.6