Prothrombin biosynthesis

Figure 13 shows the structure and absolute configuration of (2R,3S)-(-) vitamin K3 epoxide. This epoxide, prepared in optically active form by us (70) in 1976, had been known as a racemate since 1939 (78). It has recently been implicated (79) in prothrombin biosynthesis (80). The absolute configuration as shown in Figure 13 is based on the work of Snatzke (76) and the absolute rotation is [ ]436 = — 124° (acetone) and [a] = 0° ( ) (acetone). 

Cephaiexin 250-500 mg q.8 hr 95% 100% 100% 100% Rare allergic interstitial nephritis absorbed well when giyen intraperitone-ally may cause bleeding from impaired prothrombin biosynthesis Dose after dialysis Dose for GFR<10 ml/min No data... 

In normal individuals phytonadione and the menaquinones have no activity while in vitamin K deficiency the vitamin promotes the hepatic biosynthesis of factor II (prothrombin), factor VII, factor IX and factor X. Vitamin K functions as an essential cofactor for the enzymatic activation of precursors of these vitamin K dependent clotting factors. The quinone structure of the active form of vitamin K, i.e. reduced vitamin K or hydroquinone. 

Compounds with vitamin K activity (Table 6.2) are required in our diets for y-carboxyglutamate biosynthesis (Table 4.1). This amino acid is produced from certain protein glutamyl residues by carboxylation. Proteins that contain y-carboxyglutamate are blood prothrombin and coagulation factors VII, IX, and X (see Chapter 7). Other proteins of this type are osteocalcin from bone and several kidney and muscle calcium-binding proteins. 

Human milk contains about 2 xg/L of vitamin K. Vitamin K denotes a group of compounds containing the 2-methyl-1,4-naphthoquinone chemical moiety. Phylloquinone is the plant form of the vitamin and is the most prevalent homologue in milk. The vitamin is required for the biosynthesis of prothrombin and many other essential blood-clotting factors (Jensen, 1992). 

Suttie JW and Jackson CM (1977) Prothrombin structure, activation, and biosynthesis. Physiological Reviews 57, 1-70. 

The presence of Calcium (Ca ) is necessary for blood coagulation and subsequently prevents hemorrhaging from tissue injuries. The mechanism consists of cascade-type process in which stages are connected with the presence of Ca. Many of the so-called factors of blood coagulation are well known. Vitamin K is necessary in the biosynthesis of the factors IX, X, and VII and of prothrombin. The 1,25-dioxiform of vitamin D3 facilitates the process of Ca reception from the intestines. Accumulation of Ca and its release from humans is a complex system, and also includes vitamin D. 

Vitamin K is indispensable for the biosynthesis of a number of blood factors, namely prothrombin, factors VII, IX, and X. In the case of prothrombin, the vitamin is not required for the biosynthesis of the polypeptide chain. 

Stenflo, J. Vitamin K and the biosynthesis of prothrombin III. Structural comparison of an NH2-terminal fragment from normal and from dicou-marol-induced bovine prothrombin. J. biol. Chem. 248,6325-6332 (1973)... 

Plasma proteins are manufactured in the liver and their serum levels are reduced when the ability of hepatocytes to synthesize proteins is impaired. The ammonia level rises when hepatocyte damage prevents biosynthesis of amnrania to urea. Bilirubin can increase as a result of either hepatocyte dysfunction or cholestasis. Prothrombin time increases because of the reduced availability of coagulation factors normally synthesized by hepatocytes. Sorbitol dehydrogenase (SDH) is a liver-specific enzyme that is released when... 

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