Correct answer = C. FXIII is a transglutaminase that cross-links fibrin molecules in a soft clot to form a hard clot. Its deficiency does not affect the PT or aPTT tests. [Note: It is evaluated by a clot solubility test.] 5.16. Why do individuals with Scott syndrome, a rare disorder caused by mutations to scramblase in platelets, have a tendency to bleed?
Scramblase moves phosphatidylserine (PS) from the cytosolic leaflet to the extracellular leaflet in the plasma membrane of platelets. This disrupts the asymmetrical localization of membrane phospholipids created by ATP-dependent flippases (move PS from extracellular to cytosolic leaflet) and floppases (move phosphatidylcholine [PC] in the opposite direction). Having PS on the outer face of platelet membranes provides a site for protein clotting factors to interact and activate thrombin. If scramblase is inactive, PS is not available to these factors, and bleeding results.
5.10. Several days after having had their home treated for an infestation of rats, the parents of a 3-year-old girl become concerned that she might be ingesting the poison-containing pellets. After calling the Poison Hotline, they take her to the emergency department. Blood studies reveal a prolonged prothrombin and activated partial thromboplastin time and a decreased concentration of FII, FVII, FIX, and FX. Why might administration of vitamin K be a rational approach to the treatment of this patient?
Many rodent poisons are super warfarins, drugs that have a long half-life in the body. Warfarin inhibits γ-carboxylation (production of γ-carboxyglutamate, or Gla, residues), and the clotting proteins reported as decreased are the Glacontaining proteases of the clotting cascade. [Note: Proteins C and S of anticlotting are also Gla-containing proteins.] Because warfarin functions as a vitamin K antagonist, administration of vitamin K is a rational approach to treatment.
I. I. Integrative Cases
Metabolic pathways, initially presented in isolation, are, in fact, linked to form an interconnected network. The following four integrative case studies illustrate how a perturbation in one process can result in perturbations in other processes of the network.
Case 1: Chest Pain
Patient Presentation: BJ, a 35-year-old man with severe substernal chest pain of ~2 hours’ duration, is brought by ambulance to his local hospital at 5 AM. The pain is accompanied by dyspnea (shortness of breath), diaphoresis (sweating), and nausea.
Focused History: BJ reports episodes of exertional chest pain in the last few months, but they were less severe and of short duration. He smokes (2–3 packs per day), drinks alcohol only rarely, eats a “typical” diet, and walks with his wife most weekends. His blood pressure has been normal. Family history reveals that his father and paternal aunt died of heart disease at age 45 and 39 years, respectively. His mother and younger (age 31 years) brother are said to be in good health.
Physical Examination (Pertinent Findings): BJ is pale and clammy and is in distress due to chest pain. Blood pressure and respiratory rate are elevated. Lipid deposits are noted on the periphery of his corneas (corneal arcus; see left image) and under the skin on and around his eyelids (xanthelasmas; see right image). No deposits on his tendons (xanthomas) are detected.
Pertinent Test Results: BJ’s electrocardiogram is consistent with a myocardial infarction (MI). Angiography reveals areas of severe stenosis (narrowing) of several coronary arteries. Initial results from the clinical laboratory include the following:
H = High; L = Low. [Note: BJ had not eaten for ~8 hours prior to the blood draw.]