Carbohydrate Metabolism Practice Questions

Q: In hereditary fructose intolerance, which enzyme is defective?

Aldolase B. **Explanation:** **Hereditary Fructose Intolerance (HFI)** is an autosomal recessive disorder caused by a deficiency of **Aldolase B**. In the liver, fructose is first converted to Fructose-1-Phosphate (F1P) by fructokinase. Aldolase B is responsible for cleaving F1P into dihydroxyacetone phosphate (DHAP) and glyceraldehyde. When Aldolase B is defective, **Fructose-1-Phosphate accumulates** intracellularly. This "traps" inorganic phosphate, leading to ATP depletion, inhibition of glycogenolysis, and gluconeogenesis, which clinically manifests as severe postprandial hypoglycemia, vomiting, and jaundice following the introduction of fruit or formula. **Analysis of Incorrect Options:** * **A. Phosphofructokinase:** This is the rate-limiting enzyme of glycolysis. Deficiency (Tarui disease) leads to glycogen storage disease type VII, characterized by exercise intolerance and muscle cramps. * **B. Fructose 2,6-bisphosphatase:** This is a regulatory bifunctional enzyme that controls the levels of Fructose 2,6-bisphosphate, thereby regulating glycolysis and gluconeogenesis; it is not primary to HFI. * **C. Fructokinase:** Deficiency causes **Essential Fructosuria**. This is a benign condition because fructose is not "trapped" in cells; it simply spills into the urine (fructosemia and fructosuria) without causing metabolic crisis. **High-Yield Clinical Pearls for NEET-PG:** * **The "Trapping" Mechanism:** ATP depletion in HFI leads to liver failure and proximal renal tubular acidosis (Fanconi syndrome). * **Dietary Management:** Treatment requires strict avoidance of **fructose, sucrose (glucose + fructose), and sorbitol**. * **Clinical Presentation:** Symptoms typically appear when an infant is weaned from breast milk and introduced to fruits or juices. * **Reducing Sugars:** In HFI, urine dipstick for glucose is negative, but a test for reducing sugars (Benedict’s test) is positive.

Q: Which of the following does not depend on GLUT4 for glucose uptake?

Brain. **Explanation:** The core concept tested here is the distinction between **insulin-dependent** and **insulin-independent** glucose transport. **Why the Brain is the Correct Answer:** The brain is a vital organ that requires a continuous supply of glucose regardless of insulin levels. Glucose uptake in the brain (specifically across the blood-brain barrier and into neurons) is mediated primarily by **GLUT1** and **GLUT3**. These transporters are insulin-independent and have a low $K_m$ (high affinity), ensuring that the brain can sequester glucose even during fasting or hypoglycemic states. Therefore, the brain does not depend on GLUT4. **Why the Other Options are Incorrect:** * **Skeletal Muscle, Cardiac Muscle, and Adipose Tissue:** These tissues are the primary sites for **GLUT4** expression. GLUT4 is the only insulin-responsive glucose transporter. In the resting state, GLUT4 is sequestered in intracellular vesicles. Upon insulin signaling, these vesicles translocate to the plasma membrane to allow glucose entry. Consequently, these tissues are highly dependent on GLUT4 for post-prandial glucose disposal. **High-Yield NEET-PG Pearls:** * **GLUT4 Location:** Remember the mnemonic **"Muscle and Fat need 4"** (Skeletal, Cardiac, and Adipose). * **Exercise Exception:** In skeletal muscle, exercise/muscle contraction can trigger GLUT4 translocation to the membrane via an **AMPK-mediated pathway**, independent of insulin. This is why exercise helps manage blood sugar in Type 2 Diabetes. * **GLUT2:** Found in the Liver, Pancreas ($\beta$-cells), and Kidney. It has a high $K_m$ (low affinity) and acts as a glucose sensor. * **SGLT1/2:** These are active transporters (sodium-glucose co-transporters) found in the small intestine and renal tubules, unlike the GLUT family which facilitates passive diffusion.

Q: Which mucopolysaccharide/proteoglycans are present in the eye?

Keratan sulfate and chondroitin sulfate. **Explanation:** The correct answer is **D. Keratan sulfate and chondroitin sulfate**. Mucopolysaccharides (Glycosaminoglycans or GAGs) are essential components of the extracellular matrix. In the eye, specifically within the **cornea**, the transparency and structural integrity are maintained by a precise arrangement of collagen fibrils and specific GAGs. 1. **Keratan Sulfate (KS I):** This is the most abundant GAG in the cornea. It plays a critical role in maintaining corneal transparency by regulating the spacing between collagen fibrils. 2. **Chondroitin Sulfate:** Along with its isomer, Dermatan sulfate, it is found in the corneal stroma and the vitreous humor. In the cornea, Chondroitin-4-sulfate and Chondroitin-6-sulfate contribute to the hydration and osmotic pressure of the tissue. **Analysis of Incorrect Options:** * **Options A, B, & C:** While **Dermatan sulfate** is present in the cornea (often as a hybrid with chondroitin), it is primarily associated with the skin, blood vessels, and heart valves. **Heparan sulfate** is a component of cell surfaces and basement membranes (like the glomerular basement membrane) but is not a primary structural GAG of the ocular media. **NEET-PG High-Yield Pearls:** * **Keratan Sulfate I** is corneal; **Keratan Sulfate II** is found in cartilage. * **Hyaluronic acid** is the primary GAG found in the **vitreous humor** (it is the only GAG that is non-sulfated and not covalently bound to a protein). * **Macular Corneal Dystrophy** is a clinical condition caused by a defect in the sulfation of Keratan Sulfate, leading to corneal opacity. * **Heparin** has the highest negative charge density of any biological molecule.

Q: MODY 1 is caused by mutations in which of the following genes?

HNF-4 alpha. Maturity-Onset Diabetes of the Young (MODY) is a group of monogenic disorders characterized by non-insulin-dependent diabetes occurring typically before age 25, inherited in an autosomal dominant pattern [1]. **Correct Option: A (HNF-4 alpha)** MODY 1 is caused by a mutation in the **Hepatocyte Nuclear Factor-4 alpha (HNF-4α)** gene. This transcription factor is essential for the expression of genes involved in glucose transport and metabolism in pancreatic beta cells. Mutations lead to progressive beta-cell dysfunction and impaired insulin secretion. **Incorrect Options:** * **B. HNF-1 alpha:** This mutation causes **MODY 3**, which is the most common form of MODY worldwide. It is characterized by a low renal threshold for glucose (glycosuria). * **C. HNF-1 beta:** This mutation causes **MODY 5**, which is uniquely associated with renal cysts and genitourinary abnormalities (Renal Cysts and Diabetes Syndrome). * **D. Glucokinase (GCK):** This mutation causes **MODY 2**. It results in a "resetting" of the glucose sensor, leading to mild, stable fasting hyperglycemia that often does not require pharmacological treatment [1]. **High-Yield Clinical Pearls for NEET-PG:** * **Most Common MODY:** MODY 3 (HNF-1α). * **Most Common in Pregnancy:** MODY 2 (GCK). * **Treatment Sensitivity:** Patients with MODY 1 and MODY 3 are exquisitely sensitive to **Sulfonylureas**, which are the first-line treatment, often allowing patients to discontinue insulin. * **Key Diagnostic Clue:** Absence of beta-cell antibodies (GAD, IA-2) and low/normal insulin levels in a young, non-obese patient with a strong family history of diabetes.

Q: A few days after birth, a child becomes lethargic, refuses feeds, and vomits during breastfeeding. On examination, he is pot-bellied. Benedict's test is positive in urine. What is the likely reducing substance present in urine?

Galactose. ### Explanation The clinical presentation describes a classic case of **Classic Galactosemia**, typically caused by a deficiency of the enzyme **Galactose-1-phosphate uridyltransferase (GALT)**. **1. Why Galactose is the correct answer:** Symptoms of galactosemia appear shortly after birth once the infant begins breastfeeding (milk contains **lactose**, which is hydrolyzed into glucose and **galactose**). The accumulation of galactose and its metabolites leads to liver dysfunction (hepatomegaly/pot-bellied appearance), vomiting, and lethargy. Because galactose is a **reducing sugar**, it reacts positively with **Benedict’s reagent**. However, since the defect is in galactose metabolism and not glucose regulation, the urine dipstick (which uses glucose oxidase) would be negative, while the Benedict's test is positive. **2. Why the other options are incorrect:** * **Glucose:** While glucose is a reducing sugar, it is typically associated with Diabetes Mellitus. In this neonatal context, the specific trigger of breastfeeding points toward milk sugar (galactose). * **Fructose:** Fructosemia (Hereditary Fructose Intolerance) presents only after the introduction of weaning foods (fruit juices/sucrose), not during exclusive breastfeeding. * **Sucrose:** Sucrose is a **non-reducing sugar** and would yield a negative Benedict's test. **3. High-Yield Clinical Pearls for NEET-PG:** * **Enzyme Deficiency:** Most common is GALT (Classic Galactosemia). * **Key Findings:** Hepatomegaly, **Oil-drop cataracts** (due to galactitol accumulation in the lens), and intellectual disability if untreated. * **Infection Risk:** These infants are at a significantly increased risk of **E. coli neonatal sepsis**. * **Diagnosis:** Positive Benedict's test (reducing sugar) + Negative Glucose oxidase test (dipstick). * **Management:** Immediate cessation of breast milk; switch to soy-based or lactose-free formula.

Q: Substrate level phosphorylation in glycolysis is seen in which enzyme?

Pyruvate kinase. **Explanation:** **Substrate-level phosphorylation (SLP)** is the direct synthesis of ATP (or GTP) from ADP (or GDP) by the transfer of a high-energy phosphate group from a phosphorylated intermediate, without the involvement of the electron transport chain or oxygen. **1. Why Pyruvate Kinase is correct:** In the final step of glycolysis, **Pyruvate Kinase** catalyzes the conversion of Phosphoenolpyruvate (PEP) to Pyruvate. PEP contains a high-energy phosphate bond; its hydrolysis releases enough energy to drive the phosphorylation of ADP to **ATP**. This is one of the two SLP steps in glycolysis (the other being Phosphoglycerate kinase). **2. Why the other options are incorrect:** * **Succinate thiokinase (Succinyl-CoA Synthetase):** While this enzyme *does* perform substrate-level phosphorylation (converting Succinyl-CoA to Succinate and generating GTP), it occurs in the **TCA Cycle**, not glycolysis. * **Enolase:** This enzyme catalyzes the dehydration of 2-phosphoglycerate to PEP. It creates a high-energy bond but does not synthesize ATP. * **Pyruvate dehydrogenase (PDH):** This is a multi-enzyme complex that converts pyruvate to Acetyl-CoA (oxidative decarboxylation). It produces NADH but does not perform SLP. **High-Yield Clinical Pearls for NEET-PG:** * **Total SLP in Glycolysis:** 4 ATP are generated per glucose molecule (via Phosphoglycerate kinase and Pyruvate kinase). The *net* gain is 2 ATP. * **Arsenite Poisoning:** Arsenite inhibits the PDH complex. However, **Arsenate** competes with inorganic phosphate in glycolysis, bypassing the SLP step of 1,3-BPG, resulting in zero net ATP production. * **Rapoport-Luebering Cycle:** In RBCs, 1,3-BPG can be converted to 2,3-BPG. This bypasses an SLP step, meaning the RBC sacrifices ATP production to facilitate oxygen delivery to tissues.

Q: The uronic acid pathway is important for the formation of?

All of the above. The **Uronic Acid Pathway** is an alternative pathway for glucose metabolism that does not generate ATP but produces essential metabolites, primarily **UDP-glucuronate** (active glucuronic acid). ### **Why "All of the Above" is Correct:** The primary product of this pathway, UDP-glucuronate, serves three critical physiological functions: 1. **Synthesis of GAGs (Option A):** Glucuronic acid is a major structural component of Glycosaminoglycans (GAGs) like hyaluronic acid, chondroitin sulfate, and heparin. These are essential for the extracellular matrix and connective tissue. 2. **Synthesis of Glycoproteins (Option B):** Glucuronic acid is incorporated into various glycoproteins and proteoglycans, which are vital for cell signaling and membrane structure. 3. **Conjugation Reactions (Option C):** In the liver, UDP-glucuronate is used by the enzyme *UDP-glucuronyltransferase* to conjugate hydrophobic substances, making them water-soluble for excretion. This includes **bilirubin** (forming bilirubin diglucuronide), steroid hormones, and various drugs (e.g., morphine). ### **Clinical Pearls for NEET-PG:** * **Vitamin C Synthesis:** In most animals, this pathway leads to the synthesis of Ascorbic acid. However, **humans lack the enzyme L-gulonolactone oxidase**, making Vitamin C an essential dietary requirement. * **Essential Pentosuria:** A rare, benign genetic deficiency of **Xylitol dehydrogenase** leads to the excretion of L-xylulose in urine. This can give a false-positive Benedict's test (reducing sugar) but is clinically asymptomatic. * **Drug Induction:** Drugs like Phenobarbital can induce the enzymes of the uronic acid pathway, increasing the rate of glucuronidation.

Q: Fructokinase is necessary for the production of which of the following?

Fructose-1-PO4. ### Explanation **Correct Answer: A. Fructose-1-PO4** The metabolism of fructose occurs primarily in the liver through the **fructose-1-phosphate pathway**. The enzyme **Fructokinase** (also known as ketohexokinase) catalyzes the transfer of a phosphate group from ATP to the C1 position of fructose. This reaction converts fructose into **Fructose-1-phosphate (F-1-P)**. This is the first committed step of fructose metabolism and is insulin-independent. #### Why the other options are incorrect: * **B. Fructose 1,6-diphosphate:** This is formed by the action of *Phosphofructokinase-1 (PFK-1)* on Fructose-6-phosphate during glycolysis, not by fructokinase. * **C. Fructose 6-phosphate:** This is produced when fructose is phosphorylated by *Hexokinase* (a minor pathway in non-hepatic tissues like muscle). Fructokinase specifically phosphorylates the 1st carbon, not the 6th. * **D. Glyceraldehyde:** This is a downstream product. Fructose-1-phosphate is subsequently cleaved by **Aldolase B** into Dihydroxyacetone phosphate (DHAP) and Glyceraldehyde. #### NEET-PG High-Yield Clinical Pearls: 1. **Essential Fructosuria:** Caused by a deficiency of **Fructokinase**. It is a benign, asymptomatic condition where fructose is excreted in the urine (reducing sugar positive, but glucose oxidase test negative). 2. **Hereditary Fructose Intolerance (HFI):** Caused by a deficiency of **Aldolase B**. This leads to the toxic accumulation of **Fructose-1-phosphate**, which depletes intracellular inorganic phosphate, inhibiting glycogenolysis and gluconeogenesis, resulting in severe postprandial hypoglycemia and liver damage. 3. **Speed of Metabolism:** Fructose is metabolized faster than glucose because it bypasses the rate-limiting step of glycolysis (PFK-1).

Question 1

In hereditary fructose intolerance, which enzyme is defective?

Accepted Answer

Aldolase B

Answer

Phosphofructokinase

Answer

Fructose 2, 6-biphosphatase

Answer

Fructokinase

Question 2

Which of the following does not depend on GLUT4 for glucose uptake?

Accepted Answer

Brain

Answer

Skeletal muscles

Answer

Cardiac muscle

Answer

Adipose tissue

Question 3

Which mucopolysaccharide/proteoglycans are present in the eye?

Accepted Answer

Keratan sulfate and chondroitin sulfate

Answer

Keratan sulfate & dermatan sulfate

Answer

Dermatan sulfate & heparan sulfate

Answer

Dermatan sulfate & chondroitin sulfate

Question 4

MODY 1 is caused by mutations in which of the following genes?

Accepted Answer

HNF-4 alpha

Answer

HNF-1 alpha

Answer

HNF-1 beta

Answer

Glucokinase

Question 5

A few days after birth, a child becomes lethargic, refuses feeds, and vomits during breastfeeding. On examination, he is pot-bellied. Benedict's test is positive in urine. What is the likely reducing substance present in urine?

Accepted Answer

Galactose

Answer

Glucose

Answer

Fructose

Answer

Sucrose

Question 6

What is considered the most severe form of G-6-PD deficiency?

Accepted Answer

Type 3

Answer

Typed

Answer

Type 2

Answer

None of the above

Question 7

Substrate level phosphorylation in glycolysis is seen in which enzyme?

Accepted Answer

Pyruvate kinase

Answer

Succinate thiokinase

Answer

Enolase

Answer

Pyruvate dehydrogenase (PDH)

Question 8

A patient of Mediterranean ancestry was given primaquine to protect against malaria. The patient rapidly developed a hemolytic anemia due to a mostly silent mutation in which one of the following pathways or enzymes?

Accepted Answer

Hexose monophosphate shunt

Answer

Malic enzyme

Answer

Glycolysis

Answer

Gluconeogenesis

Question 9

The uronic acid pathway is important for the formation of?

Accepted Answer

All of the above

Answer

GAG (glycosaminoglycans)

Answer

Glycoproteins

Answer

Conjugation of bilirubin

Question 10

Fructokinase is necessary for the production of which of the following?

Accepted Answer

Fructose-1-PO4

Answer

Fructose 1,6-diphosphate

Answer

Fructose 6-phosphate

Answer

Glyceraldehyde

Carbohydrate Metabolism — MCQs

Carbohydrate Metabolism — MCQs

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