E. Vitamin K is required for the activation of fibrinogen. Q2. Which one of the following would increase the risk of thrombosis?
A. Excess production of antithrombin
B. Excess production of protein S
C. Expression of FV Leiden
D. Hypoprothrombinemia
E. von Willebrand disease Q3. Compare and contrast the actions of heparin and warfarin.
Focused Cases: Answers to Case-Based Questions
Case 1: Anemia with β-Thalassemia Minor
Answer = B. Transcription (synthesis of single-stranded RNA from the template strand of double-stranded DNA) requires the binding of proteins (trans-acting factors) to sequences on the DNA (cis-acting elements). Eukaryotic messenger RNA (mRNA) is monocistronic because it contains information from just one gene (cistron). The base sequence TAG (thymine adenine guanine) in the coding strand of DNA is U(uracil)AG in the mRNA. UAG is a signal that terminates translation (protein synthesis), not transcription. It is formation of the 5′-cap of eukaryotic mRNA that requires methylation (using S-adenosylmethionine), not 3′-end polyadenylation. Splicing is the spliceosome-mediated process by which introns are removed from eukaryotic mRNA and exons joined.
Answer = C. Carbon monoxide (CO) increases the affinity of hemoglobin (Hb)A for O2, thereby decreasing the ability of HbA to offload O2 in the tissues. CO stabilizes the R (relaxed) or oxygenated form and shifts the O2 dissociation curve to the left, decreasing O2 delivery (see figure at top right). The other choices decrease the affinity for O2, stabilize the T (tense) or deoxygenated form, and cause a right shift in the curve. HbA2 and fetal Hb (HbF) do not contain β globin. As β globin production decreases, synthesis of HbA2 (α2δ2) and HbF (α2γ2) increases.
Sickle cell anemia is caused by a single point mutation (A→T) in the gene for β globin that results in the replacement of glutamate by valine at the sixth amino acid position in the protein. Mutational analysis using allele-specific oligonucleotide (ASO) probes for that mutation (βS) and for the normal sequence (βA) is used in diagnosis (see figure at lower right). β-Thalassemia, in contrast, is caused by hundreds of different mutations. Mutational analysis using ASO probes can assess common mutations, including point mutations, in at-risk populations (for example, those of Greek ancestry). However, less common mutations are often not included in the panel and can be detected only by DNA sequencing.
Case 2: Skin Rash with Lyme Disease
Answer = C. Peptide-bond formation between the amino acid in the A site of the ribosome and the amino acid last added to the growing peptide in the P site is catalyzed by an RNA of the large ribosomal subunit. Any RNA with catalytic activity is referred to as a ribozyme (see figure on the next page). Formylated methionine is used to initiate prokaryotic translation. The charged initiating transfer RNA (tRNAi) is the only tRNA that goes directly to the P site, leaving the A site available for the tRNA carrying the next amino acid of the protein being made. Eukaryotic translation is inhibited by the phosphorylation of initiation factor 2 (eIF-2). The Shine-Dalgarno sequence is found in prokaryotic messenger RNA (mRNA) and facilitates the interaction of the mRNA with the small ribosomal subunit. In eukaryotes, the cap-binding proteins perform that task.