Scientific Foundations

1. Which of the following is the primary function of the urea cycle?

   1. Synthesis of glucose
   2. Conversion of ammonia to urea
   3. Production of ATP
   4. Metabolism of fatty acids

2. In which organ does the urea cycle predominantly occur?

   1. Kidney
   2. Liver
   3. Heart
   4. Muscle

3. Which enzyme is responsible for the formation of carbamoyl phosphate in the urea cycle?

   1. Ornithine transcarbamylase
   2. Carbamoyl phosphate synthetase I
   3. Arginase
   4. Arginosuccinate synthetase

4. Which compound enters the urea cycle to combine with carbamoyl phosphate?

   1. Citrulline
   2. Ornithine
   3. Arginine
   4. Aspartate

5. Allopurinol, a medication used to manage gout, works by inhibiting which enzyme?

   1. Xanthine oxidase
   2. Ribonucleotide reductase
   3. Adenosine deaminase
   4. Glutamine-PRPP amidotransferase

6. Which metabolic pathway is most directly involved in the formation of uric acid?

   1. Purine breakdown
   2. Pyrimidine metabolism
   3. Nucleotide salvage pathway
   4. De novo pyrimidine synthesis

7. What is the role of ribose-5-phosphate in purine metabolism?

   1. It inhibits xanthine oxidase.
   2. It is the substrate in the first step of purine synthesis.
   3. It is a product of purine catabolism.
   4. It is used in the synthesis of pyrimidines.

8. In purine metabolism, which of the following substances is converted to uric acid by xanthine oxidase?

   1. Hypoxanthine
   2. Adenosine.
   3. Thymidine
   4. UMP

9. Which vitamin is essential for the synthesis of purine nucleotides?

   1. Vitamin B12
   2. Vitamin C
   3. Folic acid
   4. Vitamin D

10. Where does the majority of fatty acid β-oxidation occur in the cell?

    1. Nucleus
    2. Cytosol
    3. Mitochondria
    4. Endoplasmic Reticulum

11. Which enzyme is responsible for the activation of fatty acids before β-oxidation?

    1. Carnitine acyltransferase I
    2. Acyl-CoA synthetase
    3. Acetyl-CoA carboxylase
    4. HMG-CoA reductase Reticulum

12. What is the primary product of each round of β-oxidation?

    1. NADH
    2. FADH₂
    3. Acetyl-CoA
    4. ATP

13. In the well-fed state, which of the following hormones stimulates fatty acid synthesis?

    1. Glucagon
    2. Epinephrine
    3. Insulin
    4. Cortisol

14. What is the major site of ketone body utilization?

    1. Liver
    2. Brain
    3. Adipose tissue
    4. Kidney

15. Which cofactor is essential for fatty acid synthesis?

    1. NADH
    2. FAD
    3. NADPH
    4. Coenzyme Q

16. The process of gluconeogenesis primarily occurs in which organ?

    1. Kidney
    2. Liver
    3. Muscle
    4. Adipose tissue

17. In the fed state, which organ is primarily responsible for regulating blood glucose levels?

    1. Muscle
    2. Adipose tissue
    3. Liver
    4. Brain

18. What is the main regulatory enzyme in glycolysis?

    1. Hexokinase
    2. Pyruvate kinase
    3. Phosphofructokinase-1 (PFK-1)
    4. Glucose-6-phosphate dehydrogenase

19. Which enzyme is primarily responsible for unwinding the DNA double helix during replication?

    1. DNA polymerase
    2. Topoisomerase
    3. Helicase
    4. Primase

20. What is the function of DNA primase during DNA replication?

    1. Unwinding the DNA
    2. Synthesizing the leading strand
    3. Laying down RNA primers
    4. Repairing damaged DNA

21. What is the function of DNA primase during DNA replication?

    1. Unwinding the DNA
    2. Synthesizing the leading strand
    3. Laying down RNA primers
    4. Repairing damaged DNA

22. Okazaki fragments are synthesized on which strand during DNA replication?

    1. Leading strand
    2. Lagging strand
    3. Template strand
    4. Coding strand

23. Which enzyme seals the gaps between Okazaki fragments to form a continuous DNA strand?

    1. Helicase
    2. Primase
    3. Topoisomerase
    4. DNA ligase

24. DNA polymerase has which type of proofreading activity to correct errors during replication?

    1. 5' to 3' exonuclease
    2. 3' to 5' exonuclease
    3. 5' to 3' polymerase
    4. 3' to 5' polymerase

25. Which enzyme relieves supercoiling tension in the DNA ahead of the replication fork?

    1. Topoisomerase
    2. Helicase
    3. Ligase
    4. DNA polymerase

Application Questions

1. You are designing a drug to inhibit an enzyme in the lysosome. You plan to deliver the drug inside a small liposome that will fuse with the cell membrane and release the drug into the cytosol. Which type of drug would achieve the highest concentration within lysosomes. Assume cytosol has a pH of 7.4 and lysosomes have a pH of 4.4.

   1. Drug A - weak acid pK_a = 5.4
   2. Drug B - weak acid pK_a = 6.5
   3. Drug C - weak base pK_a = 8.4
   4. Drug D - weak base pK_a = 9.4

   Show Explanation

   We need to calculate the fraction of each drug that will be charged at ph 4.4. Drug that is charged at pH 4.4 will be trapped in the lysosome. To make that calculation we use the Henderson-Hasselabalch equation: pH = pK_a + log₁₀([U]/[P]), where [U] is concentration of unprotonated drug and [P] is concentration of protonated drug. Keep in mind that an unprotonated acid is charged and unprotonated base is neutral, whereas protonated versions are uncharged and charged, respectively.

   At ph 4.4, drug D will have the largest fraction in the charged state (10000-fold more) which means more of Drug D will be trapped in the lysosomes compared to other drugs.

2. Which of the following is/are characteristic of a competitive antagonist?

   1. Inhibition by the antagonist is surmountable
   2. Potency depends on the concentration of competing agonists
   3. Inhibition typically displays use-dependence
   4. A and B

   Show Explanation

   The two key features of a competitive antagonist are: 1.) it competes with the agonist for binding to the same site, making it is impossible for both ligands to be bound to the receptor simultaneously; and, 2.) the binding of the inhibitor is reversible. This means that receptor occupancy by the agonist vs the antagonist depends on the concentration of the two competing ligands (relative to their respective equilibrium dissociation constants). If you give enough agonist, you can still produce the same maximum effect (parallel rightward shift in the agonist concentration-response curve), and the potency of the antagonist decreases as the agonist concentration is increased. Use-dependence means that the extent of inhibition increases with agonist activation of the receptor. This is a typical feature of some non-competitive inhibitors, e.g. open-channel blockers. Because use-dependence means that activation of the receptor influences inhibition by the antagonist, and for a competitive inhibitor both agonist and antagonist cannot be bound to the receptor at the same, it would be an unusual feature of a competitive antagonist.

3. A 60 kg woman has a bacterial infection. You decide to administer an antibiotic that has a volume of distribution of 0.2 L/kg. The drug has a clearance of 200 ml/min. If you administer the drug by constant intravenous infusion, approximately how long will it take for the plasma concentration of the antibiotic to reach steady-state levels?

   1. 30 min
   2. 1 hr
   3. 3 hr
   4. 24 hr

   Show Explanation

   The volume of distribution (Vd) is 12 L and the clearance is 12 L/hr. The half-life of the drug is therefore t1/2 = 0.693*12L/12L/hr, or about 40 min. Since it takes 3 to 4 half-lives to reach steady-state (120 � 160 min), the best choice is 3 hr (160 min).

4. A person who is houseless comes to your clinical and reports not having eaten in two day. The patient's serum glucose concentration is at the lower end of normal. Which source is currently allowing the patient to maintain serum glucose concentrations

   1. Amino acids
   2. Fatty acids
   3. Glycogen
   4. Ketone bodies

   Show Explanation

   Amino acids are a primary source for gluconeogenesis and allow the body to maintain serum glucose concentration after glycogen stores are exhausted. Although glycogen is a major reserve of glucose, the amount store in the liver only lasts for a day. Fatty acids and ketone bodies cannot be converted to glucose. Other sources for gluconeogenesis are glycerol and lactate, which predominate after prolonged starvation.

5. A 23-year old patient comes to your clinic with an irregular-shaped mole on their back that contains regions which differ in color. A biopsy and histological analysis indicate melanoma. The patient reports a history of tanning and extensive sun-exposure as a teenager. What type of mutation most likely led to development of the melanoma?

   1. Nucleotide deletion
   2. Nucleotide insertion
   3. Thymine dimer
   4. Nucleotide deamination

   Show Explanation

   Exposure to ultraviolet light can cause photochemical reactions between consecutive pyrimidines (usually thymine) leading to a covalent linkage between the sugar groups of the adjacent pyrimidines. Thymine dimers are the primary cause of melanoma.

6. In the patient's cells, which process is actively involved in repairing the damage from UV light?

   1. Base excision repair
   2. Nucleotide excision repair
   3. Mismatch repair
   4. Homologous recombination

   Show Explanation

   Nucleotide excision repair recognizes bulky DNA adducts that are created by pyrimidine dimers. Base excision and mismatch repair recognize small, non-distorting mutations.

7. Insulin resistance increases the demands on insulin production by β-cells in the pancreas. What change would allow $beta;-cells to meet the increase in insulin production?

   1. Metaplasia
   2. Hyperplasia
   3. Atrophy
   4. Dysplasia

   Show Explanation

   Hyperplasia is an increase in the number of cells. Having more β-cells would allow the body to increase insulin production. β-cells might also undergo hypertrophy (increase in cell size) but the gains in insulin production would be less than having more β-cells.

8. B-cell lymphoma is a cancer caused by the overproliferation of B-cells that secrete antibodies. A drug that inactivate which of the following proteins might be an effective treatment for B-cell lymphoma?

   1. Pex1
   2. Ire1
   3. Atg5
   4. SRP

   Show Explanation

   Because B-cells secrete antibody, they are prone to generating ER stress through the accumulation of unfolded protein in the ER. Inhibiting Ire1 would prevent B-cells from responding to excess unfolded protein in the ER. Eventually, prolonged ER stress would trigger apoptosis.