Carbohydrate Metabolism Practice Questions

Q: In a patient with G6PD deficiency, hemolysis is due to a decrease in which of the following?

Nicotinamide adenine dinucleotide phosphate (NADPH). **Explanation** **1. Why NADPH is the Correct Answer:** Glucose-6-Phosphate Dehydrogenase (G6PD) is the rate-limiting enzyme of the **Hexose Monophosphate (HMP) Shunt**. Its primary role in red blood cells (RBCs) is the production of **NADPH**. In RBCs, NADPH is essential for maintaining a pool of **reduced glutathione**. Reduced glutathione acts as an antioxidant that neutralizes Reactive Oxygen Species (ROS) like hydrogen peroxide ($H_2O_2$). In G6PD deficiency, the lack of NADPH leads to a depletion of reduced glutathione. Consequently, oxidative stress causes hemoglobin to denature and precipitate (forming **Heinz bodies**), damaging the RBC membrane and leading to hemolysis. **2. Why Other Options are Incorrect:** * **A. H+:** Hydrogen ion concentration relates to pH balance. While acidosis can shift the oxygen dissociation curve, it is not the primary biochemical deficit in G6PD deficiency. * **B. Thiamine pyrophosphate (TPP):** TPP is a derivative of Vitamin B1. While it is a cofactor for Transketolase (another HMP shunt enzyme), its deficiency leads to Beriberi or Wernicke-Korsakoff syndrome, not acute hemolysis. * **C. NADH:** NADH is primarily generated in glycolysis (Embden-Meyerhof pathway) and the TCA cycle. It is used by Methemoglobin Reductase to reduce Fe3+ to Fe2+, but it cannot substitute for NADPH in the glutathione reductase reaction. **3. NEET-PG High-Yield Pearls:** * **Inheritance:** X-linked recessive (more common in males). * **Triggers:** Fava beans, infections, and drugs (Sulfa drugs, Primaquine, Nitrofurantoin). * **Morphology:** **Heinz bodies** (denatured Hb) and **Bite cells** (formed when splenic macrophages remove Heinz bodies). * **Protective Effect:** G6PD deficiency provides a selective advantage against *Plasmodium falciparum* malaria.

Q: All of the following are examples of liver glycogenosis except?

Pompe disease. **Explanation:** Glycogen Storage Diseases (GSDs) are traditionally categorized based on the primary organ system affected: **Hepatic (Liver)**, **Muscular**, or **Generalized**. **Why Pompe Disease (Type II) is the correct answer:** Pompe disease is unique among GSDs because it is a **lysosomal storage disorder** caused by a deficiency of **α-1,4-glucosidase (Acid Maltase)**. Unlike other GSDs, it does not primarily manifest as a metabolic liver disorder (hypoglycemia). Instead, it is a **generalized/systemic** disease that predominantly affects the **heart and skeletal muscles**. The hallmark clinical feature is massive cardiomegaly and hypertrophic cardiomyopathy, leading to early death in the infantile form. **Why the other options are incorrect:** * **Von Gierke Disease (Type I):** The prototype of hepatic GSD. Deficiency of Glucose-6-Phosphatase leads to severe fasting hypoglycemia, hepatomegaly, and lactic acidosis. * **Hers Disease (Type VI):** Caused by a deficiency of Liver Phosphorylase. It presents as a milder form of hepatic GSD with hepatomegaly and growth retardation. * **Type III Glycogenosis (Cori/Forbes Disease):** Caused by Debranching enzyme deficiency. It affects both the liver and muscle, but it is a major cause of liver glycogenosis presenting with hepatomegaly and hypoglycemia. **High-Yield Clinical Pearls for NEET-PG:** * **Pompe = Pump:** Remember "Pompe affects the Pump (Heart)." It is the only GSD that is also a Lysosomal Storage Disease. * **Type I vs. Type III:** Both have hepatomegaly, but **Type I has lactic acidosis and hyperuricemia**, whereas Type III typically does not. * **Anderson Disease (Type IV):** Characterized by "Abnormal" glycogen (long outer branches) due to branching enzyme deficiency, leading to early liver cirrhosis.

Q: What is the net production of ATP by substrate-level phosphorylation when one molecule of fructose is converted to two molecules of pyruvate?

2. **Explanation:** The conversion of fructose to pyruvate occurs via the glycolytic pathway. To determine the **net** ATP produced by **substrate-level phosphorylation (SLP)**, we must calculate the ATP consumed versus the ATP generated. 1. **Investment Phase:** Fructose enters the pathway by being phosphorylated. In the liver (the primary site), Fructose is converted to Fructose-1-phosphate by *fructokinase*, consuming **1 ATP**. It is then cleaved into DHAP and Glyceraldehyde. Glyceraldehyde is phosphorylated to Glyceraldehyde-3-phosphate (G3P) by *triokinase*, consuming another **1 ATP**. * *Total ATP Consumed = 2.* 2. **Payoff Phase:** Each of the two G3P molecules proceeds through the remainder of glycolysis. SLP occurs at two steps: * 1,3-bisphosphoglycerate → 3-phosphoglycerate (via *phosphoglycerate kinase*): 1 ATP × 2 = 2 ATP. * Phosphoenolpyruvate → Pyruvate (via *pyruvate kinase*): 1 ATP × 2 = 2 ATP. * *Total ATP Generated via SLP = 4.* 3. **Net Yield:** 4 (Generated) - 2 (Consumed) = **2 ATP**. **Analysis of Incorrect Options:** * **B (3):** This would be the net yield if starting from Glycogen (skipping the hexokinase step), but not from free fructose. * **C (4):** This is the **gross** yield of SLP, not the **net** yield. * **D (5):** This might be confused with the total energy yield including oxidative phosphorylation (NADH), but the question specifically asks for SLP. **High-Yield Clinical Pearls for NEET-PG:** * **Essential Fructosuria:** Deficiency of *Fructokinase*; a benign condition where fructose appears in urine. * **Hereditary Fructose Intolerance (HFI):** Deficiency of *Aldolase B*; leads to trapping of Fructose-1-P, causing severe hypoglycemia and liver damage. * **Rate-limiting step:** Unlike glucose, fructose bypasses the major rate-limiting enzyme **PFK-1**, leading to more rapid lipogenesis.

Q: Which enzyme catalyzes the rate-limiting step of the pentose phosphate pathway?

Glucose-6-phosphate dehydrogenase. **Explanation:** The **Pentose Phosphate Pathway (PPP)**, also known as the Hexose Monophosphate (HMP) Shunt, occurs in the cytosol and is essential for generating **NADPH** (for reductive biosynthesis) and **Ribose-5-phosphate** (for nucleotide synthesis). **Why Option A is correct:** **Glucose-6-phosphate dehydrogenase (G6PD)** catalyzes the conversion of Glucose-6-phosphate to 6-phosphogluconolactone. This is the **first and rate-limiting step** of the oxidative phase. The enzyme is highly regulated; it is irreversibly committed to the pathway and is competitively inhibited by high levels of NADPH (feedback inhibition). **Why the other options are incorrect:** * **B. Gluconolactonase:** This enzyme acts in the second step to hydrolyze 6-phosphogluconolactone into 6-phosphogluconate. It is a rapid, non-rate-limiting reaction. * **C. 6-phosphogluconate dehydrogenase:** This catalyzes the second oxidative step (forming Ribulose-5-phosphate). While it also produces NADPH, it is not the primary regulatory checkpoint. * **D. Transketolase:** This enzyme functions in the **non-oxidative (reversible) phase**. It requires **Thiamine pyrophosphate (TPP)** as a cofactor. While clinically significant, it does not control the pathway's rate. **NEET-PG High-Yield Pearls:** * **G6PD Deficiency:** The most common enzymopathy worldwide. It leads to **hemolytic anemia** under oxidative stress (e.g., Fava beans, Primaquine, Infection) because RBCs cannot regenerate reduced glutathione due to a lack of NADPH. * **Heinz Bodies & Bite Cells:** Classic peripheral smear findings in G6PD deficiency. * **Transketolase Activity:** Measuring erythrocyte transketolase activity is the gold standard for diagnosing **Thiamine (B1) deficiency**. * **Tissue Distribution:** The HMP shunt is most active in tissues requiring fatty acid or steroid synthesis (Adrenal cortex, Liver, Mammary glands, Testes).

Q: Which of the following enzymes is stimulated by glucagon?

Glycogen phosphorylase. ### Explanation **Concept: The Glucagon-Insulin Balance** Glucagon is a catabolic hormone released during fasting. It acts via the **cAMP-Protein Kinase A (PKA) pathway**, which leads to the **phosphorylation** of key metabolic enzymes. In the liver, phosphorylation acts as a "switch" that activates degradative enzymes and inactivates synthetic enzymes. **1. Why Glycogen Phosphorylase is Correct:** Glucagon binds to G-protein coupled receptors, increasing cAMP and activating PKA. PKA phosphorylates **Phosphorylase Kinase**, which in turn phosphorylates **Glycogen Phosphorylase** (converting it from the inactive 'b' form to the active 'a' form). This triggers glycogenolysis to maintain blood glucose levels during fasting. **2. Why the Other Options are Incorrect:** * **Acetyl-CoA Carboxylase (A):** This is the rate-limiting enzyme for fatty acid synthesis. It is **inhibited** by phosphorylation (via glucagon/AMPK) and stimulated by insulin. * **Glycogen Synthase (C):** This enzyme is **inactivated** by phosphorylation. Glucagon prevents glycogen storage while promoting its breakdown. * **HMG-CoA Reductase (D):** The rate-limiting enzyme for cholesterol synthesis. Like most biosynthetic enzymes, it is **inhibited** by glucagon-mediated phosphorylation and activated by insulin. **Clinical Pearls & High-Yield Facts for NEET-PG:** * **Rule of Thumb:** Most enzymes in the **dephosphorylated** state are active under **Insulin** influence, while enzymes in the **phosphorylated** state are active under **Glucagon** influence (Exception: Glycogen Phosphorylase and Fructose-2,6-Bisphosphatase). * **Second Messenger:** Glucagon uses **cAMP**, whereas Insulin uses a **Tyrosine Kinase** signaling pathway. * **Tissue Specificity:** Glucagon acts primarily on the **liver**. It has no effect on muscle glycogen because muscle cells lack glucagon receptors.

Q: A 3-month-old infant presented with irritability, lethargy between feedings, and a potbelly. Physical examination revealed an enlarged liver. Blood work between feedings showed elevated lactate and uric acid levels, along with hypoglycemia. This child most likely has a mutation in which one of the following enzymes?

Glucose-6-phosphatase. This clinical presentation is classic for **Von Gierke Disease (Glycogen Storage Disease Type I)**. ### **Explanation of the Correct Answer** **Glucose-6-phosphatase (G6Pase)** is the final enzyme in both glycogenolysis and gluconeogenesis, responsible for converting glucose-6-phosphate into free glucose in the liver. * **Hypoglycemia:** A deficiency prevents the liver from releasing glucose into the blood during fasting. * **Hepatomegaly:** Excess glucose-6-phosphate is diverted into glycogen synthesis and lipid production, leading to a "fatty" enlarged liver (potbelly). * **Lactic Acidosis:** Accumulated G6P enters the glycolytic pathway, increasing pyruvate and lactate. * **Hyperuricemia:** Increased G6P shunts into the Pentose Phosphate Pathway, increasing ribose-5-phosphate, which drives purine synthesis and subsequent degradation to uric acid. ### **Why Other Options are Incorrect** * **A. Liver glycogen phosphorylase (Hers Disease):** While it causes hepatomegaly and mild hypoglycemia, it does **not** typically present with significant lactic acidosis or hyperuricemia because gluconeogenesis remains intact. * **B. Glycogen synthase:** Deficiency leads to fasting hypoglycemia but results in a **small liver** (no glycogen storage) and does not cause lactic acidosis. * **D. Muscle glycogen phosphorylase (McArdle Disease):** This enzyme is muscle-specific. Deficiency causes exercise intolerance and cramps, but **no hypoglycemia or hepatomegaly**, as the liver is unaffected. ### **NEET-PG High-Yield Pearls** * **GSD Type I subtypes:** Type Ia (G6Pase deficiency); Type Ib (G6P translocase deficiency—presents with **neutropenia** and recurrent infections). * **Biochemical Markers:** "Doll-like facies," hyperlipidemia (xanthomas), hyperuricemia, and lactic acidosis. * **Treatment:** Frequent oral cornstarch (slow-release glucose) and avoidance of fructose/galactose (which worsen G6P accumulation).

Q: Type II glycogen storage disorder is due to deficiency of which enzyme?

alpha-Glucosidase. **Explanation:** **Type II Glycogen Storage Disease (GSD)**, also known as **Pompe disease**, is caused by a deficiency of the lysosomal enzyme **$\alpha$-1,4-glucosidase** (also called **Acid Maltase**). Unlike other GSDs, Pompe disease is unique because it is a **Lysosomal Storage Disorder**. While most glycogen breakdown occurs in the cytosol via glycogen phosphorylase, about 1-3% of glycogen is degraded within lysosomes by $\alpha$-glucosidase. A deficiency leads to the massive accumulation of glycogen within vacuoles in nearly all tissues, most significantly affecting the heart and skeletal muscles. **Analysis of Options:** * **Option A (Correct):** $\alpha$-Glucosidase is the enzyme responsible for breaking down glycogen into glucose within lysosomes. Its deficiency leads to Pompe disease. * **Option B (Incorrect):** $\alpha$-galactosidase A deficiency causes **Fabry disease**, a sphingolipidosis characterized by angiokeratomas and renal failure. * **Option C (Incorrect):** Muscle phosphorylase deficiency causes **Type V GSD (McArdle disease)**, which presents with exercise-induced cramps and myoglobinuria. * **Option D (Incorrect):** Acid Lipase deficiency leads to **Wolman disease** or Cholesteryl Ester Storage Disease. **High-Yield Clinical Pearls for NEET-PG:** * **Mnemonic:** "Pompe affects the **Pump** (Heart)." * **Clinical Triad:** Cardiomegaly (HOCM), hypotonia ("Floppy baby"), and macroglossia. * **Key Distinction:** It is the only GSD that is also a Lysosomal Storage Disorder. * **Blood Glucose:** Unlike Type I (von Gierke), blood glucose levels are typically **normal** in Pompe disease because cytosolic glycogenolysis remains intact.

Question 1

Which compound can give rise to glucose by gluconeogenesis?

Accepted Answer

Lactate

Answer

Acetyl CoA

Answer

Palmitic acid

Answer

Fructose

Question 2

In a patient with G6PD deficiency, hemolysis is due to a decrease in which of the following?

Accepted Answer

Nicotinamide adenine dinucleotide phosphate (NADPH)

Answer

H+

Answer

Thiamine pyrophosphate (TPP)

Answer

Nicotinamide adenine dinucleotide (NADH)

Question 3

All of the following are examples of liver glycogenosis except?

Accepted Answer

Pompe disease

Answer

Von Gierke disease

Answer

Hers disease

Answer

Type III glycogenosis

Question 4

What is the net production of ATP by substrate-level phosphorylation when one molecule of fructose is converted to two molecules of pyruvate?

Accepted Answer

2

Answer

3

Answer

4

Answer

5

Question 5

A 75-year-old woman with well-controlled diabetes complains of poor eyesight. A grayish-white opacification of lens is found during a comprehensive eye examination. Which of the following metabolic pathways is most likely involved in this lens abnormality?

Accepted Answer

Aldose reductase pathway

Answer

Amino acid degradation cycle

Answer

Citric acid cycle

Answer

Oxidative phosphorylation

Question 6

Which enzyme catalyzes the rate-limiting step of the pentose phosphate pathway?

Accepted Answer

Glucose-6-phosphate dehydrogenase

Answer

Gluconolactonase

Answer

6-phosphogluconate dehydrogenase

Answer

Transketolase

Question 7

Which of the following enzymes is stimulated by glucagon?

Accepted Answer

Glycogen phosphorylase

Answer

Acetyl-CoA carboxylase

Answer

Glycogen synthase

Answer

HMG-CoA reductase

Question 8

Activity of which of the following enzymes is increased in a diabetic state?

Accepted Answer

Pyruvate dehydrogenase

Answer

Pyruvate carboxylase

Answer

PEP Carboxykinase

Answer

Glucose 6 phosphatase

Question 9

A 3-month-old infant presented with irritability, lethargy between feedings, and a potbelly. Physical examination revealed an enlarged liver. Blood work between feedings showed elevated lactate and uric acid levels, along with hypoglycemia. This child most likely has a mutation in which one of the following enzymes?

Accepted Answer

Glucose-6-phosphatase

Answer

Liver glycogen phosphorylase

Answer

Glycogen synthase

Answer

Muscle glycogen phosphorylase

Question 10

Type II glycogen storage disorder is due to deficiency of which enzyme?

Accepted Answer

alpha-Glucosidase

Answer

alpha-galactosidase

Answer

Muscle phosphorylase

Answer

Acid Lipase

Carbohydrate Metabolism — MCQs

Carbohydrate Metabolism — MCQs

On this page

Practice by Chapter

Want unlimited practice?