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

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

19. 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

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

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

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

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

22. 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

23. 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 treating patients with hypertension and prescribe an inhibitor of phosphodiesterase 4 (PDE4)to relax the smooth muscle around blood vessels to increase their diameter and reduce their resistance to blood flow. You notice in some of the patients an increase in serum glucose levels even when they have not eaten in a while. What does this suggest about glycogen breakdown in the body?

   1. Stimulated by protein kinase A
   2. Stimulated by protein kinase C
   3. Stimulated by cytosolic calcium
   4. Stimulated by MAP kinase

   Show Explanation

   Phosphodiesterase converts cAMP to 5'-AMP. Because protein kinase A is activated by cAMP, phosphodiesterase decrease the amount of active protein kinase A. Inhibiting phosphodiesterase would increase the amount of active protein kinase A and suggests that glycogen breakdown is stimulated by protein kinase A.

2. A 65-year old patient presents with a blood test indicating hypercholesterolemia. You decide to prescribe a statin which have been found to lower serum cholesterol levels. There are several types of statins. Some are lipophilic while others are hydrophilic. Which type would have the larger volume of distribution in the patient?

   1. Lipophilic
   2. Hydrophilic
   3. Neither, they would have similar volumes of distribution

   Show Explanation

   Because lipophilic statins more easily cross cell membranes they would be more readily absorbed and distributed into tissues.

3. You decide to prescribe an hydrophilic statin called pravastatin. Before prescribing the drug, you look up some information on the drug.

   • Volume of distribution = 0.5L/kg
   • Clearance = 3.5ml/min/kg

   The patient weight 70 kg. Calculate the half-life of pravastatin in the patient.

   1. 0.4 hours
   2. 1.7 hours
   3. 2.4 hours
   4. 2.4 hours

   Show Explanation

   Based on the patient's weight, the volume of distribution is 35 L and clearance is 245 ml/min or 14.7 L/hour. The following formula is used to calculate half-life: $$ half-life = \frac{0.693 * V_d}{clearance} $$ $$ half-life = \frac{0.693 * 35}{14.7} $$

4. A 42-year-old male presents to the emergency department with symptoms of confusion, ataxia, and impaired judgment. His wife mentions that he has consumed a large amount of wine over the past six hours. The patient is also on phenytoin for a seizure disorder and takes warfarin for a history of deep vein thrombosis. On physical examination, he is visibly intoxicated, with a blood alcohol concentration (BAC) of 180 mg/dL (0.18%).

   Which of the following pharmacokinetic principles best explains why continual administration of ethanol can be particularly dangerous when blood alcohol concentration is high in this patient?

   1. Michaelis-Menten kinetics resulting in first-order elimination
   2. Induction of Cytochrome P450 enzymes
   3. Zero-order elimination
   4. Competitive inhibition of aldehyde dehydrogenase

   Show Explanation

   At high blood alcohol concentrations, alcohol dehydrogenase becomes saturated and exhibits zero-order kinetics, where the rate of ethanol metabolism remains constant despite increasing ethanol levels. This saturation occurs because the enzyme is operating at or near Vmax. Unlike first-order kinetics (where the rate of elimination is proportional to the drug concentration), zero-order kinetics means that the body can only metabolize a fixed amount of the substance per unit time. Consequently, with excessive alcohol intake, the ethanol accumulates, leading to toxic effects.

5. A 55-year-old man with a history of asthma presents to his primary care physician with symptoms of exertional chest pain. His cardiac workup reveals stable angina. A pharmaceutical representative suggests prescribing a new beta-blocker that shows 50-fold selectivity for β1 over β2 receptors in vitro. Which of the following best explains why this drug might still be contraindicated in this patient?

   1. The drug's efficacy at β1 receptors is too low to provide therapeutic benefit
   2. The drug will cause complete blockade of both β1 and β2 receptors
   3. The high concentrations needed for angina treatment will result in significant β2 receptor occupancy
   4. The drug's affinity for β2 receptors increases during exercise
   5. The drug will cause desensitization of β1 receptors

   Show Explanation

   The high concentrations of beta-blocker needed to achieve therapeutic benefit in angina (especially during exercise when sympathetic drive is increased) will result in significant β2 receptor occupancy, despite the 50-fold selectivity. As explained in the text, when a concentration of the β1 antagonist that produces 91% receptor occupancy at β1 receptors is present, it will still produce 17% occupancy of β2 receptors. Even modest β2 blockade can be dangerous in asthmatics, making this drug contraindicated despite its apparent selectivity. This illustrates the important principle that drug selectivity is relative, not absolute, and that therapeutic concentrations needed for efficacy may result in significant off-target effects.

6. 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).

7. 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.

8. 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.

9. 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.