A 3-month-old African American infant presents to the hospital with 2 days of fever, "coke"-colored urine, and jaundice. The pregnancy was uneventful except the infant was found to have hyperbilirubinemia that was treated with phototherapy. The mother explains that she breastfeeds her child and recently was treated herself for a UTI with trimethoprim-sulfamethoxazole (TMP-SMX). Which of the following diseases is similarly inherited as the disease experienced by the child?
Q32
A 4-month-old boy is brought to his pediatrician for a well-child visit. His parents have noticed that he has had poor growth compared to his older siblings. The boy was delivered vaginally after a normal pregnancy. His temperature is 98.8°F (37.1°C), blood pressure is 98/68 mmHg, pulse is 88/min, and respirations are 20/min. On exam, his abdomen appears protuberant, and the boy appears to have abnormally enlarged cheeks. A finger stick reveals that the patient’s fasting blood glucose is 50 mg/dL. On further laboratory testing, the patient is found to have elevated blood lactate levels, as well as no response to a glucagon stimulation test. What enzymatic defect is most likely present?
Q33
A 24-year-old man comes to the physician because of chronic fatigue and generalized weakness after exertion. His legs feel stiff after walking long distances and he has leg cramps after climbing stairs. His symptoms are always relieved by rest. Urine dipstick shows 3+ blood and urinalysis is negative for RBCs. Baseline venous lactate and serum ammonia levels are collected, after which a blood pressure cuff is attached to the upper right arm. The patient is asked to continuously pump his right arm with the cuff inflated and additional venous samples are collected at 2-minute intervals. Analysis of the venous blood samples shows that, over time, serum ammonia levels increase and venous lactate levels remain stable. A biopsy of the right gastrocnemius muscle will most likely show which of the following?
Q34
A 52-year-old man undergoes an exercise stress test for a 1-week history of squeezing substernal chest pain that is aggravated by exercise and relieved by rest. During the test, there is a substantial increase in the breakdown of glycogen in the muscle cells. Which of the following changes best explains this intracellular finding?
Q35
An investigator is studying biomolecular mechanisms in human cells. A radioactive isotope that is unable to cross into organelles is introduced into a sample of cells. The cells are then fragmented via centrifugation and the isotope-containing components are isolated. Which of the following reactions is most likely to be present in this cell component?
Q36
A researcher is studying the properties of an enzyme that adds phosphate groups to glucose. She discovers that the enzyme is present in most body tissues and is located in the cytoplasm of the cells expressing the enzyme. She decides to mix this enzyme under subphysiologic conditions with varying levels of glucose in order to determine the kinetic properties of the enzyme. Specifically, she adds increasing levels of glucose at a saturating concentration of phosphate and sees that the rate at which glucose becomes phosphorylated gets faster at higher levels of glucose. She observes that this rate approaches a maximum speed and calls this speed Y. She then determines the concentration of glucose that is needed to make the enzyme function at half the speed Y and calls this concentration X. Which of the following is most likely true about the properties of this enzyme?
Glycolysis US Medical PG Practice Questions and MCQs
Question 31: A 3-month-old African American infant presents to the hospital with 2 days of fever, "coke"-colored urine, and jaundice. The pregnancy was uneventful except the infant was found to have hyperbilirubinemia that was treated with phototherapy. The mother explains that she breastfeeds her child and recently was treated herself for a UTI with trimethoprim-sulfamethoxazole (TMP-SMX). Which of the following diseases is similarly inherited as the disease experienced by the child?
A. Hemophilia A (Correct Answer)
B. Rett syndrome
C. Beta thalassemia
D. Sickle cell anemia
E. Marfan syndrome
Explanation: ***Hemophilia A***
- The infant's symptoms (**fever**, **coke-colored urine**, **jaundice**, and history of **hyperbilirubinemia**) following exposure to **trimethoprim-sulfamethoxazole (TMP-SMX)** suggest **glucose-6-phosphate dehydrogenase (G6PD) deficiency**, an X-linked recessive condition.
- **Hemophilia A** is also an **X-linked recessive disorder**, making its inheritance pattern similar to G6PD deficiency.
*Rett syndrome*
- **Rett syndrome** is an **X-linked dominant** neurodevelopmental disorder, primarily affecting females severely and often embryonically lethal in males.
- Its inheritance pattern differs significantly from the X-linked recessive inheritance of G6PD deficiency.
*Beta thalassemia*
- **Beta thalassemia** is an **autosomal recessive** blood disorder, meaning it is inherited through genes located on non-sex chromosomes.
- This inheritance pattern is distinct from the X-linked recessive pattern of G6PD deficiency.
*Sickle cell anemia*
- **Sickle cell anemia** is an **autosomal recessive** hereditary blood disorder, with the gene located on chromosome 11.
- Its inheritance pathway is different from the X-linked recessive genetic inheritance seen in G6PD deficiency.
*Marfan syndrome*
- **Marfan syndrome** is an **autosomal dominant** disorder affecting connective tissue, the gene for which is located on chromosome 15.
- This mode of inheritance is distinctly different from the X-linked recessive pattern of inheritance.
Question 32: A 4-month-old boy is brought to his pediatrician for a well-child visit. His parents have noticed that he has had poor growth compared to his older siblings. The boy was delivered vaginally after a normal pregnancy. His temperature is 98.8°F (37.1°C), blood pressure is 98/68 mmHg, pulse is 88/min, and respirations are 20/min. On exam, his abdomen appears protuberant, and the boy appears to have abnormally enlarged cheeks. A finger stick reveals that the patient’s fasting blood glucose is 50 mg/dL. On further laboratory testing, the patient is found to have elevated blood lactate levels, as well as no response to a glucagon stimulation test. What enzymatic defect is most likely present?
A. Alpha-1,4-glucosidase
B. Glycogen synthase
C. Alpha-1,6-glucosidase
D. Glucose-6-phosphatase (Correct Answer)
E. Glycogen phosphorylase
Explanation: ***Glucose-6-phosphatase***
- The patient's symptoms, including **hypoglycemia**, **hepatomegaly** (implied by protuberant abdomen), **lactic acidosis** (elevated lactate), and lack of response to **glucagon stimulation**, are classic for **Type I glycogen storage disease (von Gierke disease)**, which is caused by a deficiency in **glucose-6-phosphatase**.
- This enzyme is crucial for the final step of both **glycogenolysis** and **gluconeogenesis**, and its deficiency prevents the liver from releasing glucose into the bloodstream, leading to severe hypoglycemia.
*Alpha-1,4-glucosidase*
- A deficiency in **alpha-1,4-glucosidase (acid maltase)** causes **Type II glycogen storage disease (Pompe disease)**, which primarily affects muscle (cardiac and skeletal).
- Symptoms include **cardiomyopathy**, **hypotonia**, and muscle weakness, and it does **not** typically present with hypoglycemia or lactic acidosis.
*Glycogen synthase*
- A deficiency in **glycogen synthase** would lead to an inability to synthesize glycogen, resulting in **hypoglycemia** but **low** (rather than high) glycogen levels.
- Patients typically experience fasting hypoglycemia, but **no hepatomegaly** or lactic acidosis would be expected.
*Alpha-1,6-glucosidase*
- A deficiency in **alpha-1,6-glucosidase (debranching enzyme)** causes **Type III glycogen storage disease (Cori disease)**.
- This condition presents with **hepatomegaly**, **hypoglycemia**, and sometimes muscle weakness, but patients typically **do respond to glucagon** and have less severe lactic acidosis compared to Type I.
*Glycogen phosphorylase*
- A deficiency in **glycogen phosphorylase (hepatic form, Type VI GSD or Hers disease)** primarily affects the liver's ability to break down glycogen.
- This typically causes **hepatomegaly** and **hypoglycemia**, but usually, the patients **respond to glucagon** because other pathways for glucose release (like gluconeogenesis) are intact.
Question 33: A 24-year-old man comes to the physician because of chronic fatigue and generalized weakness after exertion. His legs feel stiff after walking long distances and he has leg cramps after climbing stairs. His symptoms are always relieved by rest. Urine dipstick shows 3+ blood and urinalysis is negative for RBCs. Baseline venous lactate and serum ammonia levels are collected, after which a blood pressure cuff is attached to the upper right arm. The patient is asked to continuously pump his right arm with the cuff inflated and additional venous samples are collected at 2-minute intervals. Analysis of the venous blood samples shows that, over time, serum ammonia levels increase and venous lactate levels remain stable. A biopsy of the right gastrocnemius muscle will most likely show which of the following?
A. Intrafascicular CD8+ lymphocytic infiltration
B. Endomysial fibrosis with absent dystrophin
C. Intermyofibrillar proliferation of mitochondria
D. Perivascular CD4+ lymphocytic infiltrate
E. Subsarcolemmal periodic acid–Schiff-positive deposits (Correct Answer)
Explanation: ***Subsarcolemmal acid–Schiff-positive deposits***
- The patient's symptoms (chronic fatigue, generalized weakness, leg stiffness, and cramps after exertion, relieved by rest) combined with the **ischemic forearm test** results (increased ammonia, stable lactate) are highly suggestive of **McArdle disease** (glycogen storage disease type V).
- McArdle disease is caused by a deficiency in **myophosphorylase**, leading to an inability to break down glycogen in muscles. Muscle biopsy in McArdle disease typically reveals **subsarcolemmal accumulation of glycogen**, which stains positive with periodic acid–Schiff (PAS) reagent.
*Intrafascicular CD8+ lymphocytic infiltration*
- This finding is characteristic of **polymyositis**, an inflammatory myopathy.
- Polymyositis would typically present with **progressive proximal muscle weakness** and elevated muscle enzymes, rather than activity-induced cramps and fatigue, and the ischemic forearm test would not show stable lactate.
*Endomysial fibrosis with absent dystrophin*
- This is a hallmark of **Duchenne muscular dystrophy**, a genetic disorder.
- Duchenne muscular dystrophy presents in early childhood with **progressive muscle degeneration**, Gower's sign, and significantly elevated creatine kinase, which is different from the described symptoms.
*Intermyofibrillar proliferation of mitochondria*
- This is characteristic of **mitochondrial myopathies**, such as ragged red fibers, often seen with specific stains like Gomori trichrome.
- While mitochondrial myopathies can cause exercise intolerance, the specific ischemic forearm test results (normal lactate response) do not align with a primary defect in aerobic respiration.
*Perivascular CD4+ lymphocytic infiltrate*
- This histological finding is typically associated with **dermatomyositis**, another inflammatory myopathy linked to specific skin lesions and muscle weakness.
- Dermatomyositis shares some features with polymyositis but has distinct perivascular inflammation and usually presents with pathognomonic skin rashes, which are absent in this case.
Question 34: A 52-year-old man undergoes an exercise stress test for a 1-week history of squeezing substernal chest pain that is aggravated by exercise and relieved by rest. During the test, there is a substantial increase in the breakdown of glycogen in the muscle cells. Which of the following changes best explains this intracellular finding?
A. Activation of phosphorylase kinase (Correct Answer)
B. Decrease in protein kinase A
C. Inactivation of glycogen synthase kinase
D. Activation of protein phosphatase
E. Increase in glucose-6-phosphate
Explanation: ***Activation of phosphorylase kinase***
- Exercise, particularly in the context of **ischemic heart disease** suggested by the patient's symptoms, triggers a rapid need for energy, leading to **glycogenolysis**.
- **Phosphorylase kinase** is the key enzyme that activates **glycogen phosphorylase**, the rate-limiting step in glycogen breakdown, to release glucose-1-phosphate from glycogen stores.
*Decrease in protein kinase A*
- **Protein kinase A (PKA)** is typically activated during exercise via **epinephrine** signaling, which in turn *activates* phosphorylase kinase and *inhibits* glycogen synthase.
- A decrease in PKA activity would lead to *reduced* glycogen breakdown, which contradicts the described increase in glycogen breakdown.
*Inactivation of glycogen synthase kinase*
- **Glycogen synthase kinase (GSK3)** phosphorylates and inactivates **glycogen synthase**, thereby *inhibiting* glycogen synthesis.
- If GSK3 were inactivated, glycogen synthesis would be *promoted*, rather than glycogen breakdown, further contradicting the clinical scenario.
*Activation of protein phosphatase*
- **Protein phosphatases** generally remove phosphate groups, which would *deactivate* glycogen phosphorylase and *activate* glycogen synthase.
- This action would promote glycogen synthesis and inhibit glycogen breakdown, which is the opposite of the observed physiological response during exercise.
*Increase in glucose-6-phosphate*
- While **glucose-6-phosphate** is an intermediate in glycogen metabolism, an increase in its concentration would primarily signal abundant glucose and tend to *inhibit* glycogen phosphorylase and *activate* glycogen synthase.
- This effect would favor glycogen synthesis and inhibit its breakdown, making it an unlikely explanation for increased glycogen breakdown during exercise.
Question 35: An investigator is studying biomolecular mechanisms in human cells. A radioactive isotope that is unable to cross into organelles is introduced into a sample of cells. The cells are then fragmented via centrifugation and the isotope-containing components are isolated. Which of the following reactions is most likely to be present in this cell component?
A. Glucose-6-phosphate to glucose
B. Isocitrate to α-ketoglutarate
C. Carbamoyl phosphate to citrulline
D. Fatty acyl-CoA to acetyl-CoA
E. Glucose-6-phosphate to 6-phosphogluconolactone (Correct Answer)
Explanation: ***Glucose-6-phosphate to 6-phosphogluconolactone***
- This reaction is the first step of the **pentose phosphate pathway (PPP)**, which occurs in the **cytosol**.
- Since the isotope cannot cross into organelles and is found in the cytosolic fraction, this pathway is a likely candidate.
*Glucose-6-phosphate to glucose*
- This reaction describes the dephosphorylation of **glucose-6-phosphate** to **glucose**, catalyzed by **glucose-6-phosphatase**.
- While important for glucose release, this enzyme is primarily located in the **endoplasmic reticulum** of the liver and kidneys, an organelle.
*Isocitrate to α-ketoglutarate*
- This is a step in the **Krebs cycle (citric acid cycle)**, which takes place in the **mitochondrial matrix**.
- The isotope would not be found in this compartmentalized reaction because it cannot enter organelles.
*Carbamoyl phosphate to citrulline*
- This reaction is part of the **urea cycle**, which has steps occurring in both the **mitochondrial matrix** and the cytosol. The initial step, forming carbamoyl phosphate, is mitochondrial.
- The isotope, being unable to cross into organelles, would not readily participate in the mitochondrial portion of this pathway.
*Fatty acyl-CoA to acetyl-CoA*
- This reaction represents **beta-oxidation of fatty acids**, a process that primarily occurs in the **mitochondria** and peroxisomes.
- As the isotope is excluded from organelles, it would not be involved in these reactions.
Question 36: A researcher is studying the properties of an enzyme that adds phosphate groups to glucose. She discovers that the enzyme is present in most body tissues and is located in the cytoplasm of the cells expressing the enzyme. She decides to mix this enzyme under subphysiologic conditions with varying levels of glucose in order to determine the kinetic properties of the enzyme. Specifically, she adds increasing levels of glucose at a saturating concentration of phosphate and sees that the rate at which glucose becomes phosphorylated gets faster at higher levels of glucose. She observes that this rate approaches a maximum speed and calls this speed Y. She then determines the concentration of glucose that is needed to make the enzyme function at half the speed Y and calls this concentration X. Which of the following is most likely true about the properties of this enzyme?
A. High X and high Y
B. Low X and infinite Y
C. Low X and high Y (Correct Answer)
D. Low X and low Y
E. High X and low Y
Explanation: ***Low X and high Y***
- The enzyme described is **hexokinase**, which has a **low Km (X)** and a **high Vmax (Y)**. It is found in **most body tissues** and is located in the **cytoplasm**, matching the description in the question.
- **Low Km (X)** means hexokinase has **high affinity for glucose** and reaches half its maximum velocity at low glucose concentrations (typically 0.1 mM), allowing it to phosphorylate glucose efficiently even at low physiologic glucose levels.
- **High Vmax (Y)** indicates hexokinase has a high maximum reaction rate when saturated with substrate, enabling efficient glucose phosphorylation for cellular energy needs.
- Hexokinase is the first enzyme in glycolysis and is inhibited by its product, glucose-6-phosphate, providing feedback regulation.
*High X and high Y*
- This describes **glucokinase**, which has **high Km (low affinity)** and **high Vmax**, but glucokinase is only found in **liver and pancreatic β-cells**, not "most body tissues" as stated in the question.
- Glucokinase acts as a glucose sensor and phosphorylates glucose proportionally to blood glucose concentration after meals.
*Low X and infinite Y*
- An **infinite Vmax (Y)** is impossible for any enzyme, as all enzymes have a finite maximum reaction rate when saturated with substrate.
- This violates basic enzyme kinetics principles.
*Low X and low Y*
- While **low Km (X)** correctly describes hexokinase's high affinity for glucose, **low Vmax (Y)** is incorrect.
- Hexokinase has a **high Vmax**, not low, allowing it to rapidly phosphorylate glucose in tissues with high metabolic demands.
*High X and low Y*
- **High Km (X)** indicates low affinity for glucose, requiring higher substrate concentrations to achieve half-maximal velocity, which does not match the enzyme described as being present in most tissues.
- **Low Vmax (Y)** would limit the enzyme's capacity to handle glucose, which is inconsistent with the role of the primary glucose-phosphorylating enzyme in most tissues.
