Correct answer = Translation. The gene is present and is able to be expressed as evidenced by normal production of messenger RNA. The lack of enzymic activity means that some aspect of protein synthesis is affected.
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I. OVERVIEW
Blood clotting (coagulation) is designed to rapidly stop bleeding from a damaged blood vessel in order to maintain a constant blood volume (hemostasis). Coagulation is accomplished through vasoconstriction and the formation of a clot (thrombus) that consists of a plug of platelets (primary hemostasis) and a meshwork of the protein fibrin (secondary hemostasis) that stabilizes the platelet plug. Clotting occurs in association with membranes on the surface of platelets and damaged blood vessels (Fig. 35.1). [Note: If clotting occurs within an intact vessel such that the lumen is occluded and blood flow is impeded, a condition known as thrombosis, serious tissue damage, and even death can occur. This is what happens, for example, during a myocardial infarction (MI).] Processes to limit clot formation to the area of damage and remove the clot once vessel repair is underway also play essential roles in hemostasis. [Note: Separate discussions of the formation of the platelet plug and the fibrin meshwork facilitate presentation of these multistep, multicomponent processes. However, the two work together to maintain hemostasis.]
II. FIBRIN MESHWORK FORMATION
The formation of the fibrin meshwork involves two unique pathways that converge to form a common pathway (Fig. 35.2). In each pathway, the major components are proteins (called factors [F]) designated by Roman numerals. The factors are glycoproteins that are synthesized and secreted by the liver, primarily. [Note: Several factors are also denoted by alternative names. For example, factor X (FX), the point of pathway convergence, is also known as Stuart factor.]
A. Proteolytic cascade
Within the pathways, a cascade is set up in which proteins are converted from an inactive form, or zymogen, to an active form by proteolytic cleavage in which the protein product of one activation reaction initiates another. The active form of a factor is denoted by a lowercase “a” after the numeral. The active proteins FIIa, FVIIa, FIXa, FXa, FXIa, and FXIIa are enzymes that function as serine proteases with trypsin-like specificity and, therefore, cleave a peptide bond on the carboxyl side of an arginine or lysine residue in a polypeptide. For example, FIX (Christmas factor) is activated through cleavage at arginine 145 and arginine 180 by FXIa (Fig. 35.3). The proteolytic cascade results in enormous rate acceleration, because one active protease can produce many molecules of active product each of which, in turn, can activate many molecules of the next protein in the cascade. In some cases, activation can be caused by a conformational change in the protein in the absence of proteolysis. [Note: Nonproteolytic proteins play a role as accessory proteins (cofactors) in the pathways. FIII, FV, and FVIII are the accessory proteins.]
B. Role of phosphatidylserine and calcium
The presence of the negatively charged phospholipid phosphatidylserine (PS) and positively charged calcium ions (Ca2+) accelerates the rate of some steps in the clotting cascade.
1.
Phosphatidylserine: PS is located primarily on the intracellular (cytosolic) face of the plasma membrane. [Note: Flippases create the asymmetry (see p. 205).] Its exposure signals injury to the endothelial cells that line blood vessels. PS is also exposed on the surface of activated platelets.
2.