Question 1

A 16-year-old teenager is brought to the emergency department after having slipped on ice while walking to school. She hit her head on the side of the pavement and retained consciousness. She was brought to the closest ER within an hour of the incident. The ER physician sends her immediately to get a CT scan and also orders routine blood work. The physician understands that in cases of stress, such as in this patient, the concentration of certain hormones will be increased, while others will be decreased. Considering allosteric regulation by hormones, which of the following enzymes will most likely be inhibited in this patient?

Accepted Answer

Phosphofructokinase. ***Phosphofructokinase***
  - In a stress state, **cortisol** and **epinephrine** levels are elevated, leading to increased **gluconeogenesis** and **glycogenolysis** to provide rapid energy.
  - **Allosteric inhibition** of PFK-1 occurs through multiple mechanisms:
    - **ATP** and **citrate** (high energy signals) act as direct **allosteric inhibitors** of PFK-1
    - **Glucagon** (elevated during stress) indirectly inhibits PFK-1 by reducing levels of **fructose-2,6-bisphosphate**, a potent allosteric activator
  - This inhibition of glycolysis spares glucose for critical organs like the brain and heart.

*Glucose-6-phosphatase*
  - This enzyme catalyzes the final step of **gluconeogenesis** and **glycogenolysis**, converting G6P to free glucose.
  - During stress, its activity is **stimulated** to increase blood glucose levels, not inhibited.

*Fructose 1,6-bisphosphatase*
  - This enzyme plays a key role in **gluconeogenesis**, a process vital for maintaining glucose homeostasis during stress.
  - Its activity would be **upregulated** to produce glucose, rather than inhibited.

*Pyruvate carboxylase*
  - This enzyme initiates **gluconeogenesis** by converting pyruvate to oxaloacetate in the mitochondria.
  - During stress, its activity is **stimulated** by elevated acetyl-CoA (an allosteric activator), not inhibited.

*Glycogen phosphorylase*
  - This enzyme is responsible for **glycogenolysis**, the breakdown of glycogen into glucose-1-phosphate.
  - Its activity is **stimulated** by stress hormones (epinephrine and glucagon) through cAMP-mediated phosphorylation, ensuring rapid glucose availability. [Practice more Biochemistry questions on OnCourse]

Question 2

A mother brings her newborn baby to the pediatrician after noting that his skin looks yellow. The patient's lactate dehydrogenase is elevated and haptoglobin is decreased. A smear of the child's blood is shown below. The patient is ultimately found to have decreased ability to process phosphoenolpyruvate to pyruvate. Which of the following metabolic changes is most likely to occur in this patient?

Accepted Answer

Right shift of the oxyhemoglobin curve. ***Right shift of the oxyhemoglobin curve***
  - The patient has **pyruvate kinase deficiency**, leading to decreased ATP production and a backup of glycolytic intermediates, including **2,3-bisphosphoglycerate (2,3-BPG)**.
  - Increased 2,3-BPG reduces hemoglobin's affinity for oxygen, causing a **right shift** of the oxyhemoglobin dissociation curve, which facilitates oxygen release to tissues to compensate for anemia.

*Increased ATP availability*
  - **Pyruvate kinase deficiency** impairs the final step of glycolysis, significantly reducing the net production of **ATP** in erythrocytes.
  - This lack of ATP is a primary reason for premature red blood cell destruction and the resulting hemolytic anemia.

*Left shift of the oxyhemoglobin curve*
  - A left shift indicates increased hemoglobin affinity for oxygen and would hinder oxygen delivery to tissues, which is not the compensatory mechanism seen in **pyruvate kinase deficiency**.
  - A left shift is typically caused by conditions like decreased 2,3-BPG, alkalosis, or hypothermia.

*Narrowing of the oxyhemoglobin curve*
  - The oxyhemoglobin dissociation curve does not typically "narrow"; rather, its position shifts right or left, or its slope might change.
  - "Narrowing" is not a standard description of changes to the oxyhemoglobin dissociation curve in metabolic disorders like **pyruvate kinase deficiency**.

*Broadening of the oxyhemoglobin curve*
  - Similar to "narrowing," "broadening" is not a recognized or physiologically relevant term to describe changes in the oxyhemoglobin dissociation curve.
  - The crucial alteration in conditions affecting oxygen affinity is a shift in the curve's position, reflecting changes in hemoglobin's binding capacity for oxygen. [Practice more Biochemistry questions on OnCourse]

Question 3

Researchers are investigating a new mouse model of glycogen regulation. They add hepatocyte enzyme extracts to radiolabeled glucose to investigate glycogen synthesis, in particular two enzymes. They notice that the first enzyme adds a radiolabeled glucose to the end of a long strand of radiolabeled glucose. The second enzyme then appears to rearrange the glycogen structure such that there appears to be shorter strands that are linked. Which of the following pairs of enzymes in humans is most similar to the enzymes being investigated by the scientists?

Accepted Answer

Glycogen synthase and branching enzyme. ***Glycogen synthase and branching enzyme***
  - The first enzyme described, adding a **radiolabeled glucose to the end of a long strand of radiolabeled glucose**, perfectly matches the function of **glycogen synthase**, which elongates existing glycogen chains.
  - The second enzyme, rearranging the glycogen structure to create **shorter strands that are linked**, describes the role of the **branching enzyme**, which forms α-1,6 glycosidic bonds to create branches in the glycogen molecule.

*Glycogen synthase and debranching enzyme*
  - While **glycogen synthase** does elongate glycogen chains, the **debranching enzyme** (α-1,6 glucosidase) is involved in glycogenolysis by removing glucose units at branch points, not in synthesizing shorter, linked strands during glycogen synthesis.
  - The description of the second enzyme's action is inconsistent with the role of a debranching enzyme, which breaks down branches rather than creating them in a synthetic process.

*Branching enzyme and debranching enzyme*
  - The first enzyme is described as adding a single glucose unit to the end of a strand, which is the function of **glycogen synthase**, not the branching enzyme.
  - The second enzyme's action of creating shorter, linked strands is consistent with the branching enzyme, but the initial enzyme described does not fit the role of either a branching or debranching enzyme in its initiation phase.

*Glycogen phosphorylase and branching enzyme*
  - **Glycogen phosphorylase** breaks down glycogen by removing glucose-1-phosphate units from the ends of chains, which is the opposite of the described action of adding radiolabeled glucose to the end of a strand.
  - While the **branching enzyme**'s action aligns with the second enzyme, the first enzyme's function is clearly not glycogen phosphorylase, as it is involved in synthesis, not degradation.

*Glycogen phosphorylase and glycogen synthase*
  - **Glycogen phosphorylase** is responsible for glycogen breakdown, releasing glucose-1-phosphate, and therefore cannot be the first enzyme which is involved in adding glucose to a strand.
  - While **glycogen synthase** aligns with the first enzyme, the second enzyme's action of creating shorter, linked strands is due to the **branching enzyme**, not glycogen synthase, which only extends linear chains. [Practice more Biochemistry questions on OnCourse]

Question 4

Maturity Onset Diabetes of the Young (MODY) type 2 is a consequence of a defective pancreatic enzyme, which normally acts as a glucose sensor, resulting in a mild hyperglycemia. The hyperglycemia is especially exacerbated during pregnancy. Which of the following pathways is controlled by this enzyme?

Accepted Answer

Glucose --> glucose-6-phosphate. ***Glucose --> glucose-6-phosphate***
  - This reaction is catalyzed by **glucokinase** in the pancreatic beta cells, which serves as a **glucose sensor** by controlling the rate-limiting step of glycolysis.
  - MODY type 2 is caused by mutations in the **glucokinase gene (GCK)**, leading to a higher threshold for insulin secretion and mild hyperglycemia, particularly exacerbated during pregnancy.

*Fructose-6-phosphate --> fructose-1,6-bisphosphate*
  - This step is catalyzed by **phosphofructokinase-1 (PFK-1)**, a key regulatory enzyme in glycolysis, but it is not the primary glucose sensor in pancreatic beta cells.
  - While important for glycolysis, defects in PFK-1 are associated with glycolytic enzyme deficiencies (e.g., Tarui's disease), not MODY type 2.

*Phosphoenolpyruvate --> pyruvate*
  - This final step of glycolysis is catalyzed by **pyruvate kinase**, an enzyme that is regulated but does not act as the primary glucose sensor.
  - Pyruvate kinase deficiency leads to hemolytic anemia and is not associated with MODY type 2.

*Glucose-6-phosphate --> fructose-6-phosphate*
  - This reversible isomerization step is catalyzed by **phosphoglucose isomerase**, and while part of glycolysis, it is not the rate-limiting step or the primary glucose sensing mechanism in pancreatic beta cells.
  - Defects in this enzyme are rare and not linked to MODY type 2.

*Glyceraldehyde-3-phosphate --> 1,3-bisphosphoglycerate*
  - This step is catalyzed by **glyceraldehyde-3-phosphate dehydrogenase (GAPDH)**, an important enzyme in glycolysis.
  - GAPDH is involved in energy production but is not considered the glucose sensor for insulin release, and its defects are not associated with MODY type 2. [Practice more Biochemistry questions on OnCourse]

Question 5

To maintain blood glucose levels even after glycogen stores have been depleted, the body, mainly the liver, is able to synthesize glucose in a process called gluconeogenesis. Which of the following reactions of gluconeogenesis requires an enzyme different from glycolysis?

Accepted Answer

Fructose 1,6-bisphosphate --> Fructose-6-phosphate. ***Fructose 1,6-bisphosphate --> Fructose-6-phosphate***
  - This reaction in gluconeogenesis is catalyzed by **fructose 1,6-bisphosphatase**, which is distinct from **phosphofructokinase-1** that catalyzes the reverse reaction in glycolysis.
  - This step is one of the three **irreversible steps** in glycolysis that must be bypassed by different enzymes in gluconeogenesis to ensure the unidirectional flow of the pathway.

*Glyceraldehyde 3-phosphate --> 1,3-bisphosphoglycerate*
  - This reaction is catalyzed by **Glyceraldehyde 3-phosphate dehydrogenase** in both glycolysis and gluconeogenesis, as it is a **reversible step**.
  - In gluconeogenesis, the equilibrium is shifted towards the formation of glyceraldehyde 3-phosphate due to the low concentration of products.

*2-phosphoglycerate --> 3-phosphoglycerate*
  - This is a reversible isomerization reaction catalyzed by **phosphoglycerate mutase** in both glycolysis and gluconeogenesis.
  - No unique enzyme is required for gluconeogenesis at this step.

*Dihydroxyacetone phosphate --> Glyceraldehyde 3-phosphate*
  - This reversible interconversion between these two triose phosphates is catalyzed by **triose phosphate isomerase** in both pathways.
  - These molecules are in equilibrium and can be readily converted from one to the other.

*Phosphoenolpyruvate --> 2-phosphoglycerate*
  - This is a reversible reaction catalyzed by **enolase** in both glycolysis and gluconeogenesis.
  - No distinct enzyme is needed for this step in gluconeogenesis. [Practice more Biochemistry questions on OnCourse]

Biochemistry Questions

Topics

Glycolysis

Lipid metabolism

Urea cycle

Metabolism

DNA repair

Transcription/translation

Molecular Genetics

Amino acid metabolism and disorders

Vitamin/mineral functions and deficiencies

Glycogen storage diseases

Lysosomal storage diseases

Signal transduction pathways