Glycolysis: Reactions and Regulation — MCQs
Congenital lactic acidosis is primarily due to a defect in which enzyme?
Which pathway is primarily affected in glucose-6-phosphate dehydrogenase deficiency?
Fluoride, used in the collection of blood samples, inhibits which enzyme?
Which of the following substances does not inhibit glycolysis?
Enzyme activated by decrease in Insulin: glucagon ratio:
Which of the following statements BEST describes the net ATP production in glycolysis?
The rate-limiting step in glycolysis is catalyzed by?
In glycolysis, inorganic phosphate is used in a reaction catalyzed by?
In glycolysis, which of the following enzymes is not involved?
Which of the following is an inhibitor of Phosphofructokinase-1 (PFK-1)?
Glycolysis: Reactions and Regulation Indian Medical PG Practice Questions and MCQs
Question 1: Congenital lactic acidosis is primarily due to a defect in which enzyme?
- A. Branched chain alpha-ketoacid dehydrogenase
- B. Isocitrate dehydrogenase (IDH)
- C. Transketolase
- D. Pyruvate dehydrogenase (Correct Answer)
Explanation: ***Pyruvate dehydrogenase*** - A defect in **pyruvate dehydrogenase (PDH)** complex prevents the conversion of **pyruvate to acetyl-CoA**, shunting pyruvate to **lactate production**. - This leads to an accumulation of **lactic acid** in the body, causing **congenital lactic acidosis**. *Branched chain alpha-ketoacid dehydrogenase* - A defect in **branched-chain alpha-ketoacid dehydrogenase** is responsible for **Maple Syrup Urine Disease**, not congenital lactic acidosis. - This enzyme is crucial for the metabolism of **branched-chain amino acids** (leucine, isoleucine, and valine). *Isocitrate dehydrogenase (IDH)* - **Isocitrate dehydrogenase (IDH)** is an enzyme in the **Krebs cycle** that converts isocitrate to alpha-ketoglutarate. - Defects or mutations in IDH enzymes are associated with certain **cancers**, but not primarily with congenital lactic acidosis. *Transketolase* - **Transketolase** is an enzyme involved in the **pentose phosphate pathway**, which generates NADPH and C5 sugars. - A deficiency in transketolase is associated with **Wernicke-Korsakoff syndrome** due to thiamine deficiency, not congenital lactic acidosis.
Question 2: Which pathway is primarily affected in glucose-6-phosphate dehydrogenase deficiency?
- A. Gluconeogenesis
- B. Glycolysis
- C. Pentose phosphate pathway (Correct Answer)
- D. Beta-oxidation
Explanation: ***Correct: Pentose phosphate pathway*** - Glucose-6-phosphate dehydrogenase (G6PD) is the **rate-limiting enzyme** of the pentose phosphate pathway (PPP) - G6PD deficiency leads to impaired **NADPH production**, which is critical for maintaining reduced glutathione - Reduced glutathione protects red blood cells from **oxidative damage** - Deficiency results in **hemolytic anemia** when exposed to oxidative stressors (infections, certain drugs, fava beans) *Incorrect: Gluconeogenesis* - This pathway synthesizes **glucose from non-carbohydrate precursors** (primarily in liver and kidney) - G6PD deficiency does not affect the enzymes or substrates involved in glucose synthesis - Gluconeogenesis uses different enzymes (glucose-6-phosphatase, fructose-1,6-bisphosphatase, etc.) *Incorrect: Glycolysis* - Glycolysis is the **metabolic pathway that breaks down glucose** into pyruvate to generate ATP - While glucose-6-phosphate is a substrate for both glycolysis and PPP, G6PD is **not involved in glycolysis** - G6PD deficiency specifically impacts the PPP branch, not the glycolytic enzymes *Incorrect: Beta-oxidation* - This process involves the **breakdown of fatty acids** into acetyl-CoA for energy production - Beta-oxidation is a **mitochondrial process** unrelated to G6PD function - The pentose phosphate pathway occurs in the cytoplasm and involves carbohydrate metabolism
Question 3: Fluoride, used in the collection of blood samples, inhibits which enzyme?
- A. Enolase (Correct Answer)
- B. Glucokinase
- C. Glucose-6-phosphatase
- D. Hexokinase
Explanation: ***Enolase*** - Fluoride is a potent inhibitor of **enolase**, an enzyme in the **glycolytic pathway**. - Inhibition of enolase prevents the conversion of **2-phosphoglycerate** to **phosphoenolpyruvate**, thereby halting glycolysis in collected blood samples. *Glucokinase* - Glucokinase is an enzyme primarily found in the **liver** and **pancreatic beta cells** that phosphorylates glucose. - Fluoride does not directly inhibit glucokinase; its primary site of action for preventing glycolysis in blood samples is enolase. *Glucose-6-phosphatase* - This enzyme is crucial for **glucose production** in the liver and kidneys, facilitating the dephosphorylation of **glucose-6-phosphate** to glucose. - Fluoride does not specifically target glucose-6-phosphatase as its mechanism for preventing glycolysis. *Hexokinase* - Hexokinase catalyzes the first step of glycolysis, phosphorylating **glucose to glucose-6-phosphate**. - While essential for glycolysis, hexokinase is not the primary target of fluoride's inhibitory action in blood collection, which specifically aims to stop the entire pathway further downstream at enolase.
Question 4: Which of the following substances does not inhibit glycolysis?
- A. Fluoride
- B. Arsenite
- C. Iodoacetate
- D. Fluoroacetate (Correct Answer)
Explanation: ***Fluoroacetate*** - **Fluoroacetate** is not a direct inhibitor of glycolysis. Instead, it is metabolized to **fluorocitrate**, which then acts as an inhibitor of **aconitase** in the **Krebs cycle (TCA cycle)**, thereby affecting cellular respiration at a later stage. - Its primary role in metabolic inhibition is within the **mitochondria**, impacting energy production via the TCA cycle rather than the glycolytic pathway. *Fluoride* - **Fluoride** is a known inhibitor of **enolase**, an enzyme in the penultimate step of glycolysis. - It forms a complex with **magnesium** and **phosphate** to block the active site of enolase, preventing the conversion of 2-phosphoglycerate to phosphoenolpyruvate. *Arsenite* - **Arsenite** inhibits glycolysis by targeting enzymes containing **sulfhydryl (–SH) groups**, particularly **glyceraldehyde-3-phosphate dehydrogenase (GAPDH)**, a critical enzyme in the glycolytic pathway. - It also inhibits the **pyruvate dehydrogenase complex** (linking glycolysis to the TCA cycle) and TCA cycle enzymes like **α-ketoglutarate dehydrogenase**, thereby affecting multiple stages of cellular respiration. *Iodoacetate* - **Iodoacetate** is a potent inhibitor of the enzyme **glyceraldehyde-3-phosphate dehydrogenase (GAPDH)**. - It specifically alkylates the **cysteine residue** at the active site of GAPDH, preventing the conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate, thereby blocking glycolysis.
Question 5: Enzyme activated by decrease in Insulin: glucagon ratio:
- A. PFK
- B. Glucose 6 phosphatase (Correct Answer)
- C. Glucokinase
- D. Hexokinase
Explanation: ***Glucose 6 phosphatase*** - A decreased **insulin:glucagon ratio** signifies a catabolic state, promoting glucose release into the blood. - **Glucose-6-phosphatase** is the key enzyme in **gluconeogenesis** and **glycogenolysis** in the liver, dephosphorylating **glucose-6-phosphate** to **free glucose**, which can then be exported from the liver. *PFK* - **Phosphofructokinase (PFK)** is a key regulatory enzyme in **glycolysis**, which is inhibited in a state of low insulin:glucagon ratio. - Its activity would decrease, not increase, to reduce glucose utilization. *Glucokinase* - **Glucokinase** phosphorylates glucose to **glucose-6-phosphate** in the liver, trapping it for metabolism; its activity is increased by high insulin levels. - In a low insulin:glucagon ratio, its activity would be reduced to conserve glucose. *Hexokinase* - **Hexokinase** phosphorylates glucose in most peripheral tissues but has a lower Km for glucose than glucokinase, becoming saturated even at low glucose concentrations. - Its activity is not primarily regulated by the insulin:glucagon ratio; it is generally involved in glucose uptake for cellular energy needs.
Question 6: Which of the following statements BEST describes the net ATP production in glycolysis?
- A. Glycolysis produces 2 molecules of pyruvate
- B. Glycolysis produces a net gain of 2 ATP per glucose molecule (Correct Answer)
- C. Hexokinase consumes ATP during glycolysis
- D. Aldolase catalyzes the conversion of fructose-1,6-bisphosphate into two three-carbon molecules
Explanation: ***Glycolysis produces a net gain of 2 ATP per glucose molecule*** - In the initial "investment" phase of glycolysis, **2 ATP molecules are consumed** to phosphorylate glucose. - In the subsequent "payoff" phase, **4 ATP molecules are produced** through substrate-level phosphorylation, resulting in a net gain of 2 ATP. *Glycolysis produces 2 molecules of pyruvate* - While glycolysis does produce **2 molecules of pyruvate** from one glucose molecule, this statement describes the end product of the pathway, not the net ATP production. - Pyruvate is a crucial product that can be further metabolized in aerobic or anaerobic conditions, but it does not directly represent the energy yield in terms of ATP. *Hexokinase consumes ATP during glycolysis* - **Hexokinase** is indeed the enzyme that catalyzes the first ATP-consuming step in glycolysis, phosphorylating glucose to glucose-6-phosphate. - However, this statement describes only one aspect of ATP utilization within the pathway and does not account for the total ATP produced or the overall net gain. *Aldolase catalyzes the conversion of fructose-1,6-bisphosphate into two three-carbon molecules* - **Aldolase** is a key enzyme in glycolysis responsible for cleaving **fructose-1,6-bisphosphate** into dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. - This step is part of the preparatory phase of glycolysis but does not directly describe the net ATP production.
Question 7: The rate-limiting step in glycolysis is catalyzed by?
- A. Phosphofructokinase (Correct Answer)
- B. Enolase
- C. Glucokinase
- D. Pyruvate kinase
Explanation: ***Phosphofructokinase*** - **Phosphofructokinase-1 (PFK-1)** is the primary regulatory enzyme and **rate-limiting step** in glycolysis. - It catalyzes the irreversible phosphorylation of **fructose-6-phosphate to fructose-1,6-bisphosphate**, a crucial commitment step. *Enolase* - **Enolase** catalyzes the conversion of **2-phosphoglycerate to phosphoenolpyruvate** in glycolysis. - While essential for glycolysis, it is not the rate-limiting step. *Glucokinase* - **Glucokinase** catalyzes the phosphorylation of glucose to **glucose-6-phosphate** in the liver and pancreatic beta cells. - This is the first step in glycolysis but is not the rate-limiting step for the entire pathway once glucose has entered the cell. *Pyruvate kinase* - **Pyruvate kinase** catalyzes the final step of glycolysis, converting **phosphoenolpyruvate to pyruvate**. - Although it is a regulated enzyme, it is not the primary rate-limiting step that controls the overall flux through the glycolytic pathway.
Question 8: In glycolysis, inorganic phosphate is used in a reaction catalyzed by?
- A. Enolase
- B. Pyruvate kinase
- C. Aldolase
- D. Glyceraldehyde-3-phosphate dehydrogenase (Correct Answer)
Explanation: ***Glyceraldehyde-3-phosphate dehydrogenase*** - This enzyme catalyzes the conversion of **glyceraldehyde-3-phosphate** into **1,3-bisphosphoglycerate**, incorporating inorganic phosphate (Pi) to form a high-energy phosphate bond. - This is the **only step in glycolysis** where inorganic phosphate is directly used to generate a phosphorylated intermediate, not derived from ATP. *Enolase* - Enolase catalyzes the dehydration of **2-phosphoglycerate** to form **phosphoenolpyruvate (PEP)**, which is a key high-energy intermediate. - This reaction does not involve the direct incorporation of inorganic phosphate; rather, it removes a molecule of water. *Pyruvate kinase* - Pyruvate kinase catalyzes the final step of glycolysis, transferring a phosphate group from **phosphoenolpyruvate (PEP)** to ADP, forming ATP and pyruvate. - This is a substrate-level phosphorylation step and does not involve the use of inorganic phosphate as a reactant. *Aldolase* - Aldolase cleaves **fructose-1,6-bisphosphate** into two three-carbon molecules: **dihydroxyacetone phosphate** and **glyceraldehyde-3-phosphate**. - This is a cleavage reaction and does not involve the direct incorporation of inorganic phosphate.
Question 9: In glycolysis, which of the following enzymes is not involved?
- A. Pyruvate dehydrogenase (Correct Answer)
- B. Phosphofructokinase
- C. Glucokinase
- D. Pyruvate kinase
Explanation: ***Pyruvate dehydrogenase*** - **Pyruvate dehydrogenase** is a mitochondrial enzyme complex that converts **pyruvate** to **acetyl-CoA** in the link reaction, which occurs after glycolysis and prepares for the citric acid cycle. - It is not directly involved in the ten-step glycolytic pathway itself, which converts glucose to pyruvate. *Phosphofructokinase* - **Phosphofructokinase-1 (PFK-1)** is a key regulatory enzyme in glycolysis, catalyzing the phosphorylation of **fructose-6-phosphate** to **fructose-1,6-bisphosphate**. - This step is often considered the **rate-limiting step** of glycolysis. *Glucokinase* - **Glucokinase**, located primarily in the liver and pancreatic beta cells, phosphorylates glucose to **glucose-6-phosphate** in the first step of glycolysis. - It has a high **Km** (low affinity) for glucose, allowing it to respond to high glucose concentrations. *Pyruvate kinase* - **Pyruvate kinase** catalyzes the final step of glycolysis, transferring a phosphate group from **phosphoenolpyruvate (PEP)** to ADP to form **ATP** and **pyruvate**. - This is one of the **irreversible** steps in glycolysis and a point of regulation.
Question 10: Which of the following is an inhibitor of Phosphofructokinase-1 (PFK-1)?
- A. AMP
- B. Glucose-6-phosphate
- C. Insulin
- D. Citrate (Correct Answer)
Explanation: ***Citrate*** - **Citrate** is a key allosteric inhibitor of **PFK-1**, signifying a high energy state and abundant intermediates in the **Krebs cycle**, thus slowing down glycolysis. - Its accumulation indicates that the cell has sufficient energy, reducing the need for further glucose breakdown. *AMP* - **AMP (adenosine monophosphate)** is an **allosteric activator** of PFK-1, indicating a low energy state in the cell. - High AMP levels signal the need for increased ATP production, thus stimulating glycolysis. *Glucose 6 phosphate* - **Glucose-6-phosphate** is an upstream metabolite, not a direct inhibitor of **PFK-1**; it primarily acts as an inhibitor of **hexokinase** (or glucokinase in the liver). - Its accumulation signals that the initial steps of glucose metabolism are saturated or that glucose is being diverted into other pathways. *Insulin* - **Insulin** is a hormone that **stimulates glycolysis** by increasing the synthesis of PFK-1 and other glycolytic enzymes, as well as by activating **phosphofructokinase-2 (PFK-2)** which produces **fructose-2,6-bisphosphate (F2,6BP)**. - **F2,6BP** is a potent allosteric activator of **PFK-1**, thereby *promoting* glycolysis.
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