Vitamin K is essential for activating fibrinogen, a factor that plays a role in blood clot formation. A higher risk of thrombosis can be caused by which of the following options? A) Overproduction of antithrombin, B) Overproduction of protein S, C) Expression of FV Leiden, D) Hypoprothrombinemia, or E) von Willebrand disease. 

Now let's move on to comparing and contrasting the actions of heparin and warfarin. 

Here are the answers to the case-based questions: 

Case 1: Anemia with β-Thalassemia Minor
Answer = B. Transcription involves the synthesis of single-stranded RNA from the template strand of double-stranded DNA. It requires the binding of proteins (trans-acting factors) to sequences on the DNA (cis-acting elements). Eukaryotic messenger RNA (mRNA) is monocistronic and contains information from only one gene (cistron). The base sequence TAG in the coding strand of DNA is represented as UAG in the mRNA. UAG acts as a signal to terminate translation (protein synthesis), not transcription. Methylation, using S-adenosylmethionine, is required for the formation of the 5′-cap of eukaryotic mRNA, while 3′-end polyadenylation is not involved. Splicing, which is mediated by the spliceosome, is the process by which introns are removed from eukaryotic mRNA and exons are joined.

Answer = C. Carbon monoxide (CO) increases the affinity of hemoglobin (Hb)A for oxygen (O2), leading to a decrease in HbA's ability to release oxygen in the tissues. CO stabilizes the R (relaxed) or oxygenated form of hemoglobin and causes a left shift in the oxygen dissociation curve, resulting in decreased oxygen delivery. The other options decrease the affinity for oxygen, stabilize the T (tense) or deoxygenated form of hemoglobin, 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, which results in the substitution of glutamate with valine at the sixth amino acid position in the protein. In the diagnosis of sickle cell anemia, allele-specific oligonucleotide (ASO) probes are used to detect the presence of the βS mutation (sickle cell allele) and the normal βA sequence. β-Thalassemia, on the other hand, is caused by numerous different mutations. ASO probes can be used to identify common mutations, including point mutations, in populations at risk (e.g., individuals of Greek descent). However, less common mutations can only be detected through DNA sequencing.

Case 2: Skin Rash with Lyme Disease
Answer = C. Peptide bond formation, which occurs between the amino acid in the A site of the ribosome and the amino acid most recently added to the growing peptide in the P site, is catalyzed by an RNA molecule found in the large ribosomal subunit. Any RNA with catalytic activity is referred to as a ribozyme. Prokaryotic translation is initiated using formylated methionine. The charged initiating transfer RNA (tRNAi) directly enters the P site, allowing the A site to be available for the tRNA carrying the next amino acid in the protein being synthesized. Eukaryotic translation is inhibited by the phosphorylation of initiation factor 2 (eIF-2). The Shine-Dalgarno sequence, which is present in prokaryotic mRNA, facilitates the interaction of the mRNA with the small ribosomal subunit. In eukaryotes, this task is performed by cap-binding proteins.
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.