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 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

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

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

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

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

6. Why was sequencing genomes of other organisms initially prioritized before sequencing the human genome?

   1. The technologies available were not advanced enough for sequencing the human genome.
   2. It was believed that comparative genomics with other organisms could help in understanding the human genome better.
   3. Researchers wanted to avoid the high cost associated with sequencing the human genome.
   4. The genome sequences of other organisms were thought to be more important for medical research.

   Show Explanation

   Sequencing the genomes of organisms such as bacteria, yeast, fruit flies, and nematodes was considered essential. The data from these smaller genomes would facilitate the identification of important genes in humans and allow researchers to study their functional roles more easily due to the simplicity of these organisms.

7. Which of the following vitamins leads to the formation of NAD+ and NADP+ upon metabolism?

   1. Thiamine (B1)
   2. Riboflavin (B2)
   3. Niacin (B3)
   4. Folic acid (B9)

   Show Explanation

8. Which enzyme complex does cyanide bind to, leading to cyanide poisoning?

   1. Complex I
   2. Complex II
   3. Complex III
   4. Complex IV)

   Show Explanation

9. What is the primary advantage of CRISPR technology in the context of genetically-modified mice?

   1. It is more expensive compared to traditional methods.
   2. It reduces the time required to develop genetically-modified mice.
   3. It eliminates the need for breeding in genetic modification.
   4. It is only applicable to bacterial gene modification.

   Show Explanation

   CRISPR technology has revolutionized the creation of genetically-modified mice by significantly shortening the time required for genetic modifications, from earlier techniques. It allows targeted gene knockouts, point mutations, and other modifications with higher efficiency and lower costs compared to earlier methods.

10. Which type of enzyme inhibition involves a molecule binding to the same site on the enzyme that the substrate binds and can be overcome at high substrate concentrations?

    1. Noncompetitive inhibition
    2. Allosteric inhibition
    3. Competitive inhibition
    4. Uncompetitive inhibition

    Show Explanation

    Competitive inhibition involves a molecule binding to the same site as the substrate on the enzyme. This type of inhibition can be overcome at high substrate concentrations, which can displace the inhibitor from the binding site.

11. In glycolysis, which enzyme's activity is inhibited by high levels of ATP, citrate, and H+ and activated by AMP and fructose 2,6-bisphosphate (F2,6BP)?

    1. Hexokinase
    2. Phosphofructokinase (PFK)
    3. Pyruvate kinase
    4. Glucokinase

    Show Explanation

    Phosphofructokinase (PFK) is regulated by various factors. Its activity is inhibited by high levels of ATP, citrate, and H+ ions, which signal that the cell has ample energy, thereby slowing down glycolysis. Conversely, it is activated by AMP and fructose 2,6-bisphosphate, which indicate low energy levels and hence stimulate glycolysis.

12. Which of the following enzymes in the TCA cycle is directly affected by thiamine deficiency?

    1. Citrate synthase
    2. Isocitrate dehydrogenase
    3. Alpha-ketoglutarate dehydrogenase
    4. Succinate dehydrogenase

    Show Explanation

    Thiamine (Vitamin B1) is an important cofactor for the enzyme pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase in the TCA cycle.

13. In newborns, brown fat plays an important role in the generation of heat through which of the following actions?

    1. Blocking the action of hormone-sensitive lipase
    2. Inducing shivering by leptin
    3. Promoting proton leakage into mitochondria without ATP generation
    4. Uncoupling gluconeogenesis from triglyceride hydrolysis

    Show Explanation

    Brown fat generates heat through non-shivering thermogenesis. This process involves promoting proton leakage across the mitochondrial membrane by UCP1, which uncouples oxidative phosphorylation by allowing protons to re-enter the mitochondrial matrix without generating ATP, thus dissipating energy as heat.

Application Questions

1. A 35-year-old presents with a small, non-healing wound on their foot. A biopsy of the wound and histological analysis show several undifferentiated cells but a lack of skin cells. Which protein is likely defective in the cells migrating into the wound?

   1. E-cadherin
   2. N-cadherin
   3. Desmoglein
   4. Integrin

   Show Explanation

   Integrins attach cells to the extracellular matrix and form a signaling platform that allows cells to change their behavior based on the composition of the extracellular matrix. A defect in the integrin could allow for attachment but improper signaling which could prevent differentiation of the cells in the wound.

2. A 3-week-old female infant, was brought to the clinic by her parents due to concerns of persistent lethargy, poor feeding, and recurrent vomiting. The parents report that she has become increasingly jaundiced over the past week. She initially appeared healthy at birth, but her symptoms have progressively worsened. Blood tests show the child is hypoglycemic (2.5 mmol/L) and has elevated levels of several liver enzymes. Genetic sequencing finds a mutation in GALT (Galactose-1-Phosphate Uridyltransferase). What condition does the child have?

   1. Fructose intolerance
   2. Lactose intolerance
   3. Galactosemia
   4. Essential fructosuria

   Show Explanation

   Galactosemia is most commonly caused by a deficiency in the enzyme UDP-glucose:α-D-galactose 1-phosphate uridylyltransferase. This deficiency prevents the conversion of D-galactose into D-glucose, leading to the accumulation of D-galactose and D-galactose 1-phosphate in the blood and tissues, causing various health issues including liver damage.

3. Pulsatile administration of parathyroid hormone (PTH) has been found to increase bone density by stimulating osteoblasts to synthesize bone but have minimal impact on osteoclast development. If you analyzed the genome around the COL1A1 gene in osteoblasts exposed to PTH what change would you observe compared to unstimulated osteoblasts?

   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.

4. 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.

5. 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.

6. 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.

7. A 45-year-old patient presents to the clinic with a recent history of frequent urination and increased thirst. Laboratory tests indicate elevated glucose levels in the urine, which suggests a reduced ability to transport glucose across the epithelium in the kidney. Which protein is most likely reduced in the kidney epithelial cells?

   1. SGLT2
   2. CFTR (chloride channel)
   3. Claudin 5
   4. Sodium-potassium-chloride channel

   Show Explanation

   SGLT2 channel co-transports sodium and glucose across the apical membrane from lumenal fluid (in this case urine). Fewer SGLT2 channels would reduce the efficiency of of glucose absorption by the epithelium, leading to elevated levels of glucose in the urine.

8. A patient presents with blood and protein in their urine. A biopsy of the kidney is taken and the sample shows a slight separation of the kidney epithelium from the underlying tissue. Which protein is most likely defective in the patient?

   1. Cadherin
   2. Claudin
   3. Type II collagen
   4. Type IV collagen

   Show Explanation

   Type IV collagen is major component of the basement membrane which underlies all epithelia. A mutation that changed the structure of type IV collagen could reduce the integrity of the basement membrane and affect the binding of epithelial cells to the basement membrane.

9. 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.

10. 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 channel

    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).

11. 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 pathological changes. Below is image of a bronchiole from a biopsy. How would you classify the epithelium?

    

    1. Simple squamous
    2. Stratified squamous
    3. Simple columnar
    4. Stratified columnar

    Show Explanation

    The epithelium in the image is simple columnar. Note the single layer of cells with slightly elongated nuclei. 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.

12. How would the epithelium change in response to prolonged exposure to smoke from wild fires?

    1. Become cuboidal
    2. Develop more cilia
    3. Become stratified
    4. Develop more mucous-secreting cells

    Show Explanation

    Stratified epithelia offer more protection from mechanical force and exposure to environmental chemicals and toxins. More cilia would generate more efficient movement of mucous up the airway but not protect the tissue from foreign toxins. More mucous might provide some protection but would also block the airway, reducing the flow of air through the bronchiole. Note how the normal bronchiole has few, if any, mucous-secreting cells.