Scientific Foundations

Recall Questions

1. Which of the following is the primary molecule used by cells to store and transfer energy?

   1. Glucose
   2. ATP
   3. NADH
   4. Pyruvate

2. Which molecule acts as the final electron acceptor in the electron transport chain?

   1. Oxygen
   2. NADH
   3. FADH₂
   4. Carbon Dioxide

3. Which molecule acts as the final electron acceptor in the electron transport chain?

   1. Oxygen
   2. NADH
   3. FADH₂
   4. Carbon Dioxide

4. Which of the following reactions is an example of a coupled reaction?

   1. Glucose + Oxygen → CO₂ + Water
   2. ATP + Glucose → ADP + Glucose-6-phosphate
   3. Pyruvate → Lactate
   4. ADP + P_i → ATP

5. The conversion of NAD⁺ to NADH during glycolysis is an example of which type of process?

   1. Phosphorylation
   2. Oxidation
   3. Reduction
   4. Hydrolysis

6. NADPH is primarily involved in which type of cellular processes?

   1. Catabolic
   2. Anabolic
   3. Glycolytic
   4. Fermentation

7. What is the role of transfer RNA (tRNA) in translation?

   1. To unwind the DNA double helix
   2. To match amino acids with the mRNA codons
   3. To synthesize RNA from a DNA template
   4. To match amino acids with the mRNA codons

8. What is the significance of the start codon in mRNA?

   1. It marks the end of translation.
   2. It signals the beginning of transcription.
   3. It indicates the start of protein synthesis.
   4. It is responsible for mRNA splicing.

9. What is a mutation or variant?

   1. A change in the amino acid sequence of a protein
   2. A change in the DNA sequence of a gene
   3. A modification in the RNA sequence of a transcript
   4. A change in the ribosomal RNA during translation

10. What is the function of a promoter in gene expression?

    1. To initiate the translation
    2. To signal the end of transcription
    3. To provide a binding site for RNA polymerase and other transcription factors
    4. To stabilize the mRNA molecule

11. What is the primary function of the 5' cap and poly-A tail in eukaryotic mRNA?

    1. To facilitate the export of mRNA from the nucleus
    2. To stabilize the mRNA and protect it from degradation
    3. To aid in the correct folding of the mRNA
    4. To enhance the transcription of the gene

Application Questions

1. PTH stimulates osteoblasts to synthesize RANKL (RANK ligand). If you analyzed histones on the RANKL gene in osteoblasts after addition of PTH, what change would you expect?

   1. Acetylated histones
   2. Deacetylated histones
   3. More histones
   4. Fewer histones

   Show Explanation

   Activate transcription of genes is often associated with acetylation of the histones near the gene. Acetylation adds an acetyl group to a lysine on histones, removing the positive charge on the lysine. Without the positive charge, the histones associate less strongly to DNA (the positive charge interacted with the negative charge on the phosphate group in DNA), resulting in a more open chromatin structure that is amenable to transcription.

2. Bisphosphanates are often used to treat osteoporosis. The structure of a typical bisphosphanate is shown below. They contain phosphate groups and chemical groups that induce apoptosis? The effectiveness of bisphosphanates in increasing bone density depends on which activity in osteoclasts.

   

   1. Acid secretion
   2. Collagenase secretion
   3. RANK receptor expression
   4. Endocytosis

   Show Explanation

   Bisphosphanates contain phosphate groups which allow them to be incorporated into bone matrix, which is a combination of collagen and calcium-phosphate crystals. When osteoclasts dissolve bone, the take up many of the digested components via endocytosis, which allows those components to be recycled. If osteoclasts digest bone into which bisphosphanates has crystalized, the will take up the bisphosphonate by endocytosis, and the apoptotic groups will induce cell death in the osteoclasts.

3. Although bisphosphanates are often used to treat osteoporosis, some recent studies have linked long-term use of bisphosphanates (> 3 years) with an increase risk of fractures in the femur. What might explain the increase in fractures associated with long-term use of bisphosphanates?

   1. Decrease endochondrial ossification
   2. Decrease intramembraneous ossification
   3. Decrease in bone modeling
   4. Decrease in bone remodeling

   Show Explanation

   Bisphosphanates reduce osteoclast activity by inducing apoptosis. The decrease in osteoclast activity reduces reabsorption of bone to increase bone density, but it also reduces bone remodeling which replaces old bone with new bone. This could allow accumulation of small cracks in bone that weakens its structural integrity.

4. In addition to collagen, osteoblasts also secrete osteopontin which contains a domain that interacts with integrins. Loss of osteopontin is also associated with decrease in bone strength. What best explains osteopontin's role in bone metabolism?

   1. Attachment of osteoclasts to bone
   2. Collagen secretion
   3. Calcium-phosphate crystallization
   4. Collagenase activation

   Show Explanation

   To digest bone, osteoclasts must first attach to bone and form a seal to prevent diffusion of acid and collagenase away from the surface of bone. Osteoclasts use integrins to attach to components of bone. Osteoclasts express αvβ3 integrin which binds osteopontin.

5. You are studying different muscle tissue and measuring the rate at which each contracts. To initiate contraction, you apply an electrical stimulus to each muscle type. You notice that smooth muscle starts to contract much longer after stimulation than skeletal and cardiac muscle. What accounts for this delayed response in smooth muscle cells?

   1. Slower rate of myosin activation
   2. Slower rate of calcium channels opening
   3. Slower rate of tropomyosin movement
   4. Slower rate of sodium channels opening

   Show Explanation

   Contraction of smooth muscle is triggered through a signaling pathway that leads to a phosphorylation of myosin light chains. Phosphorylated light chains activate the myosin motor which can generate tension on actin filaments and lead to cell contraction. In skeletal and cardiac muscle, the myosin motor is already in active state and only requires a small shift in the position of tropomyosin along actin filaments to initiate contraction. The process of shifting tropomyosin is much faster than the several steps that lead to phosphorylation of myosin light chain.

6. You are working with a neurologist to identify biopsies that show damage to motor neurons that innervate skeletal muscle cells. The biopsies show axons of several different types, and you must quickly identify axons which are most likely part of a motor neuron. Which type would you look for?

   1. 1 µm diameter, unmyelinated
   2. 1 µm diameter, myelinated
   3. 10 µm diameter, myelinated
   4. 10 µm diameter, unmyelinated

   Show Explanation

   Motor neurons that innervate skeletal muscle tissue must be able to generate action potentials with fast conduction velocities. Conduction velocity increases with an increase in axon diameter and with myelination of the axon, but myelination has much larger impact on conduction velocity than axon diameter.

7. Alport Syndrome is caused by mutations in a gene that encodes a type IV collagen. The disease mostly likely affects which of the following?

   1. Long bones
   2. Achilles tendon
   3. Kidney epithelium
   4. Knee cartilage

   Show Explanation

   Type IV collagen is major component of the basement membrane which underlies all epithelia.

8. You run a routine blood test on a patient, and the results show hypomagnesium (low serum magnesium). Urinalysis reveals above normal levels of magnesium. Genome sequencing shows a mutation in claudin 19. Through which pathway does magnesium pass across the epithelium in the kidney?

   1. Magnesium channel
   2. Transcytosis
   3. Paracellular diffusion
   4. Magnesium pump

   Show Explanation

   The mutation in claudin 19 suggests magnesium passes across the epithelium paracellularly because claudin 19 is a key component of tight junctions which regulate paracellular transport.

9. Assuming most magnesium is reabsorbed in the kidney through the paracellular route, which channel would epithelial cells in the kidney express in their apical membrane to create the driving force to absorb magnesium from the lumen of the kidney tube into the interstitial fluid?

   1. Sodium channel
   2. Chloride channel
   3. Potassium channel
   4. Calcium pump

   Show Explanation

   Because the concentration of magnesium in urine and interstitial fluid is similar, the epithelium would need to create a positive fluid in the lumen (urine) that would drive magnesium across the epithelium into interstitial fluid. A potassium channel would generate a lumen positive fluid because potassium has an electrochemical potential that favors its diffusion from the cytosol into the lumen fluid. Sodium and calcium electrochemical gradients favor their diffusion into cells. Chloride's electrochemical gradient slightly favors it moving out of cells, but this would create a negatively charged fluid in the lumen (urine).

10. You are working with a group of people who worked several years as firefighters for US Forest Service. Many of the people in the group show signs of respiratory disease, including emphysema and obstructive lung disease. You have been asked to screen biopsies for the evidence of obstructive lung disease which can be diagnosed by a change in the epithelia of bronchioles from a normal simple columnar. Below is image of a bronchiole from a biopsy. How would you characterize the epithelium?

    

    1. Normal
    2. Hyperplastic
    3. Metaplastic
    4. Dysplastic

    Show Explanation

    The epithelium in the image is simple columnar. Note the single layer of cells with slightly elongated nuclei. The epithelium would be considered normal. The wavy nature of the epithelium is normal for a bronchiole and is due to a slight constriction of bronchiole. In a fully open bronchiole, the epithelium would appear less wavy.

11. You are studying an inherited form of muscle weakness. You identify a mutation in a gene that encodes a potassium channels. The mutation increases the probability that the channel is open. You analyze the electrophysiology of the skeletal muscle cells from the affected patients and discover that the muscle cells require higher concentrations of acetylcholine to generate contraction. What is the most likely explanation for the change in the skeletal muscle cells?

    1. Increase in amount of acetylcholine receptors
    2. Increase in the threshold potential
    3. Increase in the overshoot potential
    4. Increase in membrane potential

    Show Explanation

    The threshold potential is defined as an unstable membrane potential where the influx of sodium ions equals the outflow of potassium ions. Action potentials are triggered when membrane potential becomes more positive than the threshold potential. To reach the threshold potential enough ligand-gated and voltage-gated sodium channels must open to oppose the outward flow of potassium. Acetylcholine triggers the opening on ligand-gated sodium channels which allows the inward flow of sodium and makes membrane potential more positive. As membrane potential increases, voltage-gated sodium channels begin to open, allowing more sodium to enter the cell and further increasing membrane potential. If a sufficient number of voltage-gated sodium channels open, membrane potential will exceed the threshold potential and the cell will commit to firing an action potential. A mutation in a potassium channel that increased its probability of being open would increase the flow of potassium out of the cell and require more voltage-gated sodium channels to open to oppose the outward flow of potassium. Opening more voltage-gated sodium channels would require the cell to reach a higher membrane potential. Consequently, the threshold potential will increase because a higher (most positive) membrane potential is needed to trigger an action potential.