Glycolysis

Glycolysis US Medical PG Question 1: 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

Glycolysis 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.

Glycolysis US Medical PG Question 2: Certain glucose transporters that are expressed predominantly on skeletal muscle cells and adipocytes are unique compared to those transporters found on other cell types within the body. Without directly affecting glucose transport in other cell types, which of the following would be most likely to selectively increase glucose uptake in skeletal muscle cells and adipocytes?

• A. Increased plasma glucose concentration
• B. It is physiologically impossible to selectively increase glucose uptake in specific cells
• C. Increased levels of circulating insulin (Correct Answer)
• D. Decreased plasma glucose concentration
• E. Decreased levels of circulating insulin

Glycolysis Explanation: ***Increased levels of circulating insulin*** - Insulin stimulates the translocation of **GLUT4 transporters** from intracellular vesicles to the cell membrane in **skeletal muscle** and **adipocytes**, thereby increasing glucose uptake. - This mechanism is **selective** because other cell types (e.g., brain, liver) primarily use insulin-independent glucose transporters (e.g., GLUT1, GLUT2, GLUT3) that are constitutively active or respond to different signals. *Increased plasma glucose concentration* - While increased glucose concentration would drive glucose uptake in many cells, it is not **selective** for skeletal muscle and adipocytes since other cells also take up glucose. - Insulin-independent tissues would also increase glucose uptake, making this a non-specific effect. *It is physiologically impossible to selectively increase glucose uptake in specific cells* - This statement is incorrect because the body has mechanisms, such as **insulin-mediated GLUT4 translocation**, that specifically regulate glucose uptake in certain cell types like skeletal muscle and adipocytes. - This regulatory specificity is crucial for maintaining **glucose homeostasis**. *Decreased plasma glucose concentration* - A decrease in plasma glucose would generally **reduce** glucose uptake across all cell types, including skeletal muscle and adipocytes. - It would not selectively increase uptake in any specific cell population. *Decreased levels of circulating insulin* - Decreased insulin levels would lead to **reduced** glucose uptake in insulin-sensitive tissues like skeletal muscle and adipocytes, as GLUT4 transporters would remain sequestered intracellularly. - This would result in higher circulating glucose levels rather than increased uptake.

Glycolysis US Medical PG Question 3: A 14-year-old female with no past medical history presents to the emergency department with nausea and abdominal pain. On physical examination, her blood pressure is 78/65, her respiratory rate is 30, her breath has a fruity odor, and capillary refill is > 3 seconds. Serum glucose is 820 mg/dL. After starting IV fluids, what is the next best step in the management of this patient?

• A. Intravenous Dextrose in water
• B. Subcutaneous insulin glargine
• C. Intravenous regular insulin (Correct Answer)
• D. Intravenous glucagon
• E. Subcutaneous insulin lispro

Glycolysis Explanation: ***Intravenous regular insulin*** - The patient presents with **diabetic ketoacidosis (DKA)**, characterized by **hyperglycemia**, **fruity breath** (due to ketones), and **hypotension**. Prompt administration of **intravenous regular insulin** is crucial to lower blood glucose and resolve ketoacidosis. - **Regular insulin** is preferred intravenously due to its **rapid onset** and short duration of action, allowing for precise titration and continuous adjustment based on glucose levels. *Intravenous Dextrose in water* - **Dextrose** would further increase the already severely elevated blood glucose level in a patient with DKA, worsening the metabolic derangements. - Dextrose is typically initiated only after blood glucose drops to safe levels (<200 mg/dL) to prevent **hypoglycemia** during insulin infusion. *Subcutaneous insulin glargine* - **Insulin glargine** is a **long-acting insulin** designed for basal insulin coverage, not for acute management of severe hyperglycemia or DKA. - Its **slow onset of action** and prolonged effect make it unsuitable for the urgent and rapid glucose reduction required in DKA. *Intravenous glucagon* - **Glucagon** is a hormone that **raises blood glucose levels**, counteracting the effects of insulin. - Administering glucagon would exacerbate the severe hyperglycemia present in DKA and is used only in cases of severe hypoglycemia. *Subcutaneous insulin lispro* - **Insulin lispro** is a **rapid-acting insulin analog** but is typically given subcutaneously. - While faster than regular insulin subcutaneously, the **subcutaneous route** has variable absorption in critically ill patients, and the immediate and precisely controllable effect of intravenous regular insulin is needed in DKA.

Glycolysis US Medical PG Question 4: An 11-year-old boy is brought to the emergency room with acute abdominal pain and hematuria. Past medical history is significant for malaria. On physical examination, he has jaundice and a generalized pallor. His hemoglobin is 5 g/dL, and his peripheral blood smear reveals fragmented RBC, microspherocytes, and eccentrocytes (bite cells). Which of the following reactions catalyzed by the enzyme is most likely deficient in this patient?

• A. Glucose-1-phosphate + UTP → UDP-glucose + pyrophosphate
• B. Glucose + ATP → Glucose-6-phosphate + ADP + H+
• C. D-glucose 6-phosphate → D-fructose-6-phosphate
• D. Glucose-6-phosphate + H2O → glucose + Pi
• E. D-glucose-6-phosphate + NADP+ → 6-phospho-D-glucono-1,5-lactone + NADPH + H+ (Correct Answer)

Glycolysis Explanation: ***D-glucose-6-phosphate + NADP+ → 6-phospho-D-glucono-1,5-lactone + NADPH + H+*** - This reaction is catalyzed by **glucose-6-phosphate dehydrogenase (G6PD)**, an enzyme critical for the production of **NADPH** in the **pentose phosphate pathway**. - **NADPH** is essential for reducing **oxidative stress** in red blood cells. A deficiency in G6PD leads to increased susceptibility to hemolysis, especially under oxidative triggers like malaria, resulting in symptoms such as **acute hemolytic anemia**, jaundice, and specific morphological changes (e.g., **fragmented RBCs**, **microspherocytes**, and **eccentrocytes**, also known as **bite cells**). *Glucose-1-phosphate + UTP → UDP-glucose + pyrophosphate* - This reaction is catalyzed by **UDP-glucose pyrophosphorylase** and is important for **glycogen synthesis**. - A deficiency in this enzyme would primarily affect glycogen metabolism and would not explain the **hemolytic anemia** or the characteristic red blood cell morphology seen in the patient. *Glucose + ATP → Glucose-6-phosphate + ADP + H+* - This reaction is catalyzed by **hexokinase**, the first committed step in **glycolysis**. - While hexokinase deficiency can cause **hemolytic anemia**, it generally presents with chronic, moderate anemia and does not typically involve the specific red blood cell morphology (eccentrocytes/bite cells) associated with oxidative damage found in G6PD deficiency. *D-glucose 6-phosphate → D-fructose-6-phosphate* - This reaction is catalyzed by **phosphoglucose isomerase** (also known as phosphohexose isomerase) and is part of **glycolysis**. - A deficiency in this enzyme would impair glycolysis and lead to **hemolytic anemia**, but its clinical presentation and RBC morphology differ from what is typically seen in G6PD deficiency, particularly the absence of oxidative stress markers like bite cells. *Glucose-6-phosphate + H2O → glucose + Pi* - This reaction is catalyzed by **glucose-6-phosphatase**, an enzyme found primarily in the liver and kidney, responsible for the final step in **gluconeogenesis** and glycogenolysis to release free glucose into the bloodstream. - A deficiency in glucose-6-phosphatase leads to **glycogen storage disease type I (Von Gierke's disease)**, characterized by **hypoglycemia**, **lactic acidosis**, and hepatomegaly, not hemolytic anemia.

Glycolysis US Medical PG Question 5: An 8-year old boy is brought to the emergency department because he has been lethargic and has had several episodes of nausea and vomiting for the past day. He has also had increased thirst over the past two months. He has lost 5.4 kg (11.9 lbs) during this time. He is otherwise healthy and has no history of serious illness. His temperature is 37.5 °C (99.5 °F), blood pressure is 95/68 mm Hg, pulse is 110/min, and respirations are 30/min. He is somnolent and slightly confused. His mucous membranes are dry. Laboratory studies show: Hemoglobin 16.2 g/dL Leukocyte count 9,500/mm3 Platelet count 380,000/mm3 Serum Na+ 130 mEq/L K+ 5.5 mEq/L Cl- 99 mEq/L HCO3- 16 mEq/L Creatinine 1.2 mg/dL Glucose 570 mg/dL Ketones positive Blood gases, arterial pH 7.25 pCO2 21 mm Hg Which of the following is the most appropriate next step in management?

• A. Intravenous hydration with 0.45% normal saline and insulin
• B. Intravenous hydration with 5% dextrose solution and 0.45% normal saline
• C. Intravenous sodium bicarbonate
• D. Intravenous hydration with 0.9% normal saline and insulin (Correct Answer)
• E. Intravenous hydration with 0.9% normal saline and potassium chloride

Glycolysis Explanation: ***Intravenous hydration with 0.9% normal saline and insulin*** - This patient presents with **diabetic ketoacidosis (DKA)**, characterized by hyperglycemia (glucose 570 mg/dL), metabolic acidosis (pH 7.25, HCO3- 16 mEq/L, ketones positive), and dehydration (dry mucous membranes, increased thirst, weight loss). - Initial management of DKA involves aggressive **volume expansion** with **0.9% normal saline** to restore perfusion and reduce hyperglycemia; subsequently, **insulin infusion** is started to correct hyperglycemia and halt ketogenesis. *Intravenous hydration with 0.45% normal saline and insulin* - While insulin is crucial, **0.45% normal saline (hypotonic saline)** is generally not the initial fluid of choice for DKA due to the risk of exacerbating cerebral edema, especially in children. - **Isotonic saline (0.9% normal saline)** is preferred for initial resuscitation to rapidly restore extracellular fluid volume. *Intravenous hydration with 5% dextrose solution and 0.45% normal saline* - **5% dextrose solution** should only be added to intravenous fluids when the blood glucose level falls to around 200-250 mg/dL, to prevent hypoglycemia while continuing insulin to resolve ketosis. - Administering dextrose initially would worsen the existing severe hyperglycemia. *Intravenous sodium bicarbonate* - **Sodium bicarbonate** is generally not recommended for mild to moderate DKA due to potential risks like cerebral edema and metabolic alkalosis, and potential paradoxical worsening of CNS acidosis. - Bicarbonate therapy is reserved for **severe acidosis (pH < 6.9 or 7.0)** with hemodynamic instability or impaired cardiac contractility, which is not the case here. *Intravenous hydration with 0.9% normal saline and potassium chloride* - While **0.9% normal saline** is appropriate, this option lacks **insulin therapy**, which is essential for treating DKA by halting ketogenesis and correcting hyperglycemia. - Although potassium supplementation will be necessary during DKA treatment (as insulin drives K+ into cells and can cause hypokalemia), the most appropriate **next step** is to initiate both fluid resuscitation and insulin therapy together. - The patient's current potassium level of 5.5 mEq/L is at the upper limit of normal, but reflects total body potassium depletion; potassium should be added to maintenance fluids once adequate urine output is established.

Glycolysis Flashcard 1 of 5

Question: Pyruvate kinase defiency results in increased levels of _____, which causes decreased Hb affinity for O2

Answer: 2,3-BPG

Glycolysis Flashcard 2 of 5

Question: Hexokinase is characterized by a _____ Vmax relative to glucokinase

Answer: low

Glycolysis Flashcard 3 of 5

Question: Which steps (2) of glycolysis produce ATP? _____

Answer:

Glycolysis Flashcard 4 of 5

Question: Which steps (2) of glycolysis require ATP? _____

Answer:

Glycolysis Flashcard 5 of 5

Question: Pyruvate kinase is regulated via positive feedback by _____ (glycolysis)

Answer: fructose-1,6-bisphosphate