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. 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

7. To which enzyme complex does cyanide bind, leading to cyanide poisoning?

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

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8. 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.

9. 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.

10. 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.

11. 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 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.

2. A 3-day-old male newborn is brought to the emergency department with seizures and progressive lethargy. He was born full-term via uncomplicated vaginal delivery. He fed poorly since birth. Initial workup reveals a normal glucose level. The pediatrician suspects a metabolic disorder but the diagnosis is initially missed. Which laboratory finding would most likely confirm the diagnosis?

   1. Elevated phenylalanine
   2. Elevated ammonia
   3. Elevated branched-chain amino acids
   4. Decreased methionine
   5. Elevated methylmalonic acid

   Show Explanation

   Carbamoyl Phosphate Synthetase I (CPS I) Deficiency is a urea cycle disorder presenting in newborns with seizures, progressive lethargy, and coma due to toxic ammonia accumulation. The disorder leads to elevated levels of ammonia.

   Elevated phenylalanine is seen in phenylketonuria and presents with musty odor and intellectual disability but not neonatal seizures or coma

   Elevated branched-chain amino acids is seen in maple syrup urine disease and presents with burnt-sugar smelling diapers

   Decreased methionine is seen in homocystinuria and is associated with cardiovascular disease and elevated homocysteine.

   Elevated methylmalonic acid is seen in vitamin B12 deficiency and typically in strict vegans or their breastfed infants.

3. An 8-year-old boy with acute myelogenous leukemia begins chemotherapy. Three days later, he develops fever, severe ankle pain, and hematuria. Laboratory workup reveals elevated uric acid, hyperkalemia, hyperphosphatemia, and elevated creatinine. Which of the following best explains the elevated uric acid levels in this patient?

   1. Decreased excretion of pyrimidines
   2. Increased degradation of purines
   3. Deficiency of HGPRT
   4. Inhibition of xanthine oxidase
   5. Accumulation of orotic acid

   Show Explanation

   In Tumor Lysis Syndrome, massive cell death from chemotherapy releases large amounts of nucleic acids. The purines are catabolized, leading to urate overproduction and crystal deposition in joints and renal tubules

   Pyrimidines are not degraded into uric acid; uric acid is exclusively the end product of purine catabolism

   Deficiency of HGPRT causes Lesch-Nyhan Syndrome, a congenital disorder with self-mutilation and neurological symptoms

   Inhibition of xanthine oxidase is the mechanism of Allopurinol, which is used to treat elevated uric acid. Inhibition would decrease uric acid levels

   Accumulation of orotic acid is seen in hereditary orotic aciduria, which is a pyrimidine synthesis disorder.

4. A 45-year-old woman with type 2 diabetes is started on Metformin. After 3 months, her fasting blood glucose improves significantly from 145 mg/dL to 98 mg/dL. Her physician explains that the drug works primarily by reducing hepatic glucose output. Which of the following enzymes is most directly inhibited by Metformin's mechanism of action?

   1. Pyruvate Carboxylase
   2. PEP Carboxykinase
   3. Fructose-1,6-Bisphosphatase
   4. Glucose-6-Phosphatase
   5. Pyruvate Kinase

   Show Explanation

   Metformin increases AMP levels in hepatocytes, and AMP directly inhibits Fructose-1,6-Bisphosphatase, which blocks gluconeogenesis. This reduces glucose output from the liver and lowers fasting glucose levels.

   Pyruvate carboxylase catalyzes the conversion of pyruvate into oxaloacetate, but it is not a target of metformin.

   PEP carboxykinase catalyzes the conversion of oxaloacetate to phosphoenolpyruvate, using GTP as a co-factor. The enzyme is not a target of metformin.

   GLucose-6-phosphatase generates free glucose which is released into the blood, but it is not a target of metformin.

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   Pyruvate kianse is a glycolytic enzyme.