Factor III

Dismption of the endothehal surface of blood vessels expose coUagen fibers and connective tissue. These provide surfaces that promote platelet adherence, platelet release reaction, and subsequent platelet aggregation. Substances Hberated from the platelets stimulate further platelet aggregation, eg, adenosine diphosphate maintain vasoconstriction, eg, serotonin and participate in blood coagulation, eg, platelet Factors III and IV. In addition, the release reaction modifies platelet membranes in a manner that renders phosphoHpid available for coagulation. The thrombin [9002-04-4] elaborated by the coagulation mechanism is a potent agent in the induction of the platelet release reaction. 

Factors I, II, III, V, VII, VIII, IX, X, XI, XII, and XIII, Protein C, and Protein S are synthesized in the Hver. Factor III is present in many different organs throughout the body. Factor IV is the divalent cation calcium. The concentration of calcium required for normal function of the blood coagulation system is much less than required for normal physiologic function of many organs in the body, eg, myocardium. 

Factor IX. This factor is dependent on the presence of vitamin K for its activity as a biologicaUy functional procoagulant glycoprotein. Factor IX is converted to its active form by XIa in the classic scheme of the intrinsic pathway. However, it can also be activated via interaction with Factor Xa or the complex Factor III plus Factor VII in the presence of calcium. 

In 1973, the first naturally occurring isobacteriochlorin, iron-containing siroheme, was isolated1 from a sulfite reductase of Escherichia coli. Later it was also discovered in sulfite and nitrite reductases of numerous bacteria and plants.2 Iron-free sirohydrochlorins (also called factor II) were discovered in vitamin B12 producing bacteria.3-4 Together with factor III. a sirohydrochlorin methylated in the 20-position, the reduced forms of factor II and factor III were identified as biosynthetic intermediates in the biosynthesis of vitamin B12.5... 

The result is that Factor III of 2.2.6. given above imposes further symmetry restrictions on the 32 point groups and we obtain a total of 231 space groups. We do not intend to delve further into this aspect of lattice contributions to crystal structure of solids, and the factors which cause them to vary in form. It is sufficient to know that they exist. Having covered the essential parts of lattice structure, we will elucidate how one goes about determining the structure for a given solid. 

Moroder, L., Bovermann, G., Mouricr, G., Gohring, W., Gemeiner, M., and Wiinsch, E. (1987) Studies on immunoassays of peptide factors. III. Gastrin/iso-1-cytochrome c as immunogen for raising anti-gas-trin antisera. Biol. Chem. Hoppe-Seyler, 368, 839-848. 

Two coagulation factors function uniquely in the extrinsic pathway factor III (tissue factor) and factor VII. Tissue factor is an integral membrane protein present in a wide variety of tissue types (particularly lung and brain). This protein is exposed to blood constituents only upon rupture of... 

Electrochemical sensors have several disadvantages with respect to optical sensors (i) they are based on electrodes and require a reference electrode (ii) the liquid-liquid junction is easily perturbed by external factors (iii) they are sensitive to electrical interferences (iv) miniaturization is not easy and their cost is relatively high. However, optical sensors also have some disadvantages (i) ambient light can interfere (ii) the range over which the concentration of an analyte can be accurately measured is often limited (iii) they have generally limited long-term stability. 

Extrinsic pathway Coagulation is activated by release of tissue thromboplastin, a factor not found in circulating blood. Clotting occurs in seconds because factor III bypasses the early reactions. 

Extrinsic pathway This pathway has fewer steps than the intrinsic pathway and occurs rapidly, within a matter of seconds if the trauma is severe. It is called the extrinsic pathway because a protein tissue factor, also called thromboplastin or coagulation factor III, takes into the blood stream from outside and initiates the formation of prothrombinase. Tissue factor is released from the surface of the damaged cells. It activates factor VII. Factor VII combines with factor X, activating it. Factor X in the presence of Ca combines with factor V to give active enzyme prothrombinase. 

Subsequently both a monomethyl and a trimethyl isobacteriochlorin, factors I (78) and III (79), have been isolated from P. shermanii and shown by radiolabelling experiments to act as precursors of cobyrinic acid in cell-free systems. While sirohydrochlorin (77) and factor III (79) are incorporated when administered in their oxidized forms, factor I (78) and uroporphyrin III (80) (the oxidized form of uroporphyrinogen III) are only effectively incorporated when added in the reduced forms (78a) and (70), suggesting that the four compounds are intermediates only at their reduced levels and that a cellular reductase system exists which is capable of reducing (77) and (79) but not (78) and (80). 

The structure of factor III, the trimethyl isobacteriochlorin, is worthy of note. Preliminary studies had suggested the structure (81), which was in better accord with a subsequent ring contraction to the corrinoid skeleton involving oxidation at C-20 followed by extrusion of formaldehyde. However, the 13C NMR spectrum of factor III (as its octamethyl ester) enriched biosynthetically with [13CH3]methionine and [5-13C]ALA (Scheme 25) shows both the meso and meso- methyl carbons as doublets, a feature in accord with substitution of... 

Scheme 25 l3C NMR of biosynthetically 13C-enriched factor III octamethyl ester. The (J =44.2 Hz) doub-let/centre line intensities for C-20 and the C-20 methyl reflect a higher degree of enrichment from [5-l3C]ALA than from [13CH3]methionine. Additional fine structure of the C-20 signal is due to long-range coupling with C-4... 

Scheme 26 Conversion of radiolabelled factor III (79) to cobyrinic acid (analyzed as cobester, 75a) and acetic acid by cell-free extracts of P. shermanii and Clostridium tetenomorphum. Labelling patterns = 3H, = 14C or...

Analogues of vitamin Bi2 are known in which the dimethylbenzimidazole is replaced by other bases it is 5-hydroxybenzimidazole in Factor III, adenine in pseudo-vitamin Bj2, 2-methyladenine in Factor A and 2-methylhypoxanthine in Factor H. Where adenine units occur, they are linked to ribose through position 7, rather than position 9 as in other adenine nucleosides. 

Figure 6. Elution profile obtained on examination of the gel permeation behavior of 14C acetylated S. aureus Factor III. Cytochrome-c and fluorescein labeled E. coli HPr were included in the applied sample as internal standards. Absorbance at 410 nm (cytochrome-c), fluorescein fluorescence (HPr), and radioactivity (Factor III) are plotted vs. fraction number. Inset shows the elution profiles for the external (blue dextran) and internal (fiuoroglycine) column markers. Data in this figure are from unpublished work (20).

Ill, which had been radioactively labeled by 14C acetylation. Cyto-chrome-c and fluorescein labeled E. coli HPr, a protein of known sequence, have been added to the sample as internal molecular weight standards. The Mapp determined for Factor III by gel permeation in 6M GuHCl, 11,000 300, is in good agreement with the value obtained from sedimentation equilibrium in 6M GuHCl-O.lM 2-mercaptoethanol, 12,000 (20). 

The substituents present at the 20 position are characteristic of this structure the methyl group is present in Factor III, an intermediate in the biological conversion of uroporphyrinogen to Vitamin B12- The hydroxyl group represents the hypothetical subsequent biological transformation. Their presence is essential for ring contraction in the absence of the 20-methyl group the conversion to the corrin skeleton does not occur, but there is tautomerizaton to a keto form [69, 79-81],... 

Some hemophilia A and B patients develop antibodies against FVIII and FIX, respectively. This complicates the direct administration of these proteins. An alternative in these cases is treatment with active factor VII (FVIIa), which complexes with factor III in the presence of phospholipids and Ca2+, activating factor X, which, in normal patients, is activated by active factors VIII and IX. The commercial name of recombinant FVIIa expressed in BHK cells and produced by Novo-Nordisk is NovoSeven (Table 16.1). 

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