Through hypothetical clinical cases and research scenarios, this activity will challenge your understanding of carbohydrate metabolism, amino acid metabolism, oxidative phosphorylation, and enzymes.
With 25 questions, in this section, you’ll explore real-world applications of biochemistry, sharpen your critical thinking, and connect biochemical concepts to clinical insights. Dive in, think deeply, and discover the fascinating intricacies of metabolic pathways.
Good luck, and let the challenge begin!
1. A Medical Biochemistry professor assigned a task to a learning group to create a table linking glycolytic intermediates with other metabolic pathways. The students submitted the following table:
| Glycolytic Intermediate | Pathway |
| Glucose 6-phosphate | Glycogenesis, Glycogenolysis, Gluconeogenesis, HMP Pathway |
| Fructose 6-phosphate | Fructose Metabolism, Gluconeogenesis, HMP Pathway |
| Glyceraldehyde 3-phosphate | Electron Transport Chain, Gluconeogenesis, HMP Pathway |
| 1,3-Bisphosphoglycerate | Gluconeogenesis, Rapoport-Leubering Shunt |
| Phosphoenolpyruvate | Gluconeogenesis |
| Pyruvate | Various fates |
The professor, however, pointed out that the students missed an important direct link between a glycolytic intermediate and lipid metabolism. Which glycolytic intermediate should have been included in the table to reflect this connection?
A. Dihydroxyacetone phosphate
B. Fructose 1,6-bisphosphate
C. 3-Phosphoglycerate
D. 2-Phosphoglycerate
E. Lactate
Correct Answer: A. Dihydroxyacetone phosphate
Explanation:
Dihydroxyacetone phosphate (DHAP) connects glycolysis to lipid metabolism by serving as a precursor for glycerol-3-phosphate, which is crucial for triglyceride and phospholipid synthesis.
2. The Professor asked the students to create a flowchart detailing the roles of Acetyl CoA, including its involvement in key pathways and cycles. The students completed the task, but the professor noted they missed Acetyl CoA’s role as a regulator of enzyme activities. Which of the following enzymes is positively modified by Acetyl CoA?
A. Acetyl CoA carboxylase
B. Pyruvate carboxylase
C. Pyruvate dehydrogenase complex
D. Pyruvate kinase
E. Glycogen phosphorylase
Correct Answer: B. Pyruvate carboxylase
Explanation:
Acetyl CoA acts as a positive allosteric activator of pyruvate carboxylase, an enzyme critical for gluconeogenesis. It signals the need for oxaloacetate production to support the citric acid cycle when Acetyl CoA levels are high.
3. The professor asked students about the portal of entry of an amino acid into the TCA cycle that is positively charged at physiological pH, produced in the urea cycle, and serves as a precursor to an important smooth muscle relaxant. Which amino acid fits these criteria?
A. Glutamate
B. Glutamine
C. Arginine
D. Ornithine
E. Aspartate
Correct Answer: C. Arginine
Explanation:
Arginine is positively charged at physiological pH (due to its guanidinium group), is a product of the urea cycle, and serves as a precursor for nitric oxide (NO), a potent smooth muscle relaxant. Nitric oxide is synthesized from arginine by the enzyme nitric oxide synthase (NOS).
4. In a patient with vitamin B12 deficiency, which of the following substrates will not be available for glucose synthesis?
A. Lactate
B. Propionyl CoA
C. Glycerol
D. Alanine
E. Leucine
Correct Answer: B. Propionyl CoA
Explanation:
Vitamin B12 is required for the conversion of methylmalonyl CoA (produced from propionyl CoA) to succinyl CoA, an intermediate in the TCA cycle that can be used for gluconeogenesis. In vitamin B12 deficiency, this pathway is disrupted, and propionyl CoA cannot enter the gluconeogenic pathway, making it unavailable for glucose synthesis. Other substrates like lactate, glycerol, and alanine have alternative pathways independent of vitamin B12 for gluconeogenesis. Leucine, being ketogenic, is not a glucose precursor.
5. In a patient with vitamin B12 deficiency, which of the following amino acids should not be restricted in the diet?
A. Valine
B. Alanine
C. Methionine
D. Isoleucine
E. Threonine
Correct Answer: B. Alanine
Explanation:
Alanine is a key glucogenic amino acid and does not rely on vitamin B12 for its metabolism or entry into gluconeogenesis. It is converted to Pyruvate, which directly participates in glucose synthesis. In contrast, amino acids like valine, isoleucine, methionine, and threonine are metabolized to propionyl CoA, which requires vitamin B12 for further conversion to succinyl CoA. These pathways are impaired in vitamin B12 deficiency, making their metabolism problematic. Therefore, alanine is safe and should not be restricted in the diet.
6. The professor asked the students about the reduced availability of a gluconeogenic substrate in a patient presenting with sideroblastic anemia, which is linked to vitamin B6 deficiency. Which of the following important substrates would be less available in this clinical state?
A. Lactate
B. Propionyl CoA
C. Glycerol
D. Alanine
E. Leucine
Correct Answer: D. Alanine
Explanation:
Vitamin B6 (pyridoxine) is a cofactor for aminotransferase reactions, such as the conversion of alanine to Pyruvate via alanine aminotransferase (ALT). In vitamin B6 deficiency, this conversion is impaired, reducing the availability of Pyruvate for gluconeogenesis. Other substrates like lactate and glycerol do not require vitamin B6 for their pathways into gluconeogenesis. Propionyl CoA and leucine are also unaffected by vitamin B6 directly, though leucine is ketogenic and not a significant glucose precursor.
7. The professor asked the students to identify a glycolytic intermediate that acts as a positive allosteric modifier of a regulatory enzyme in the glycolytic pathway. Which of the following is most likely that activator?
A. Glucose 6-phosphate
B. Fructose 1,6-bisphosphate
C. Fructose 2,6-bisphosphate
D. 1,3-Bisphosphoglycerate
E. Phosphoenolpyruvate
Correct Answer: B. Fructose 1,6-bisphosphate
Explanation:
Fructose 1,6-bisphosphate is a glycolytic intermediate that serves as a positive allosteric activator of pyruvate kinase, a key regulatory enzyme in glycolysis. This activation helps coordinate the later stages of glycolysis by ensuring efficient conversion of phosphoenolpyruvate to Pyruvate. Other options either do not act as allosteric modifiers (e.g., glucose 6-phosphate) or regulate enzymes indirectly through different pathways (e.g., fructose 2,6-bisphosphate acts on phosphofructokinase-1).
8. The professor asked the students to identify the likely fate of Pyruvate in a patient with thiamine deficiency, such as a chronic alcoholic. Which of the following is the most likely possibility?
A. Acetyl CoA
B. Alanine
C. Lactate
D. Acetyl CoA and Alanine
E. Acetyl CoA and Lactate
F. Alanine and Lactate
Correct Answer: F. Alanine and Lactate
Explanation:
In thiamine deficiency, the activity of the pyruvate dehydrogenase complex (PDC) is impaired because thiamine is a cofactor for this enzyme. Consequently, Pyruvate cannot be converted into acetyl CoA effectively. Instead, Pyruvate is shunted towards two alternative pathways:
1. Alanine formation via alanine aminotransferase (ALT).
2. Lactate formation via lactate dehydrogenase (LDH) leading to lactic acidosis.
This explains why both alanine and lactate are the dominant fates of Pyruvate under these conditions.
9. The professor asked the students to identify the likely fate of Pyruvate following thiamine treatment and complete alcohol abstinence in a previously thiamine-deficient patient. Which of the following is the most likely possibility?
A. Acetyl CoA
B. Alanine
C. Lactate
D. Acetyl CoA and Alanine
E. Acetyl CoA and Lactate
F. Alanine and Lactate
Correct Answer: A. Acetyl CoA
Explanation:
With thiamine treatment and alcohol abstinence, the functionality of the pyruvate dehydrogenase complex (PDC) is restored. Pyruvate is now efficiently converted into acetyl CoA, which enters the TCA cycle for energy production. The pathways leading to alanine and lactate production are no longer favored because there is no longer a block in the conversion of Pyruvate to acetyl CoA. Thus, acetyl CoA becomes the primary fate of pyruvate post-treatment.
10. A recently diagnosed hypertensive patient has been prescribed an antihypertensive drug that lowers the Vmax of an enzyme. What is the most likely mechanism of inhibition of this drug?
A. Competitive
B. Non-competitive
C. Uncompetitive
D. Allosteric inhibition
E. Suicidal inhibition
Correct Answer: B. Non-competitive
Explanation:
Non-competitive inhibition occurs when an inhibitor binds to an enzyme at a site other than the active site, altering the enzyme’s structure or function. This reduces the enzyme’s maximum velocity (Vmax) because the enzyme-inhibitor complex cannot catalyze the reaction, even if substrate concentration is high. Unlike competitive inhibition, Km remains unchanged because substrate binding to the active site is not directly affected. This mechanism aligns with the description of the drug’s action.
11. The activities of many enzymes, membrane transporters, and other proteins can be quickly activated or inactivated by phosphorylation of specific amino acid residues. Which of the following best identifies this type of regulation?
A. Allosteric modification
B. Covalent modification
C. Induction
D. Repression
E. Feedforward regulation
Correct Answer: B. Covalent modification
Explanation:
Phosphorylation is a type of covalent modification where a phosphate group is added to specific amino acid residues (commonly serine, threonine, or tyrosine) by kinases. This modification alters the activity, localization, or stability of the protein, allowing rapid and reversible regulation. It is distinct from allosteric modification, which involves non-covalent interactions, and from induction/repression, which are transcriptional controls.
12. A coal mine worker was brought to the emergency room in an unconscious state following a blast in the mine. His blood carboxyhemoglobin level was high, and he was diagnosed with carbon monoxide (CO) poisoning. CO is a known inhibitor of the electron transport chain. Which of the following components is inhibited by CO?
A. Complex I
B. Complex II
C. Complex III
D. Complex IV
E. ATP/ADP transporter
F. ATP synthase complex
Correct Answer: D. Complex IV
Explanation:
CO binds tightly to the heme iron in cytochrome a3 of Complex IV (cytochrome c oxidase) in the electron transport chain. This prevents the transfer of electrons to oxygen, the final electron acceptor, effectively halting the chain and reducing ATP production. This inhibition is responsible for the cellular hypoxia seen in CO poisoning. Other complexes and components are not directly affected by CO.
13. Which of the following statements is not true of competitive inhibitors?
A. Vmax remains the same
B. Km is increased
C. Inhibitor is a structural analog of the substrate
D. Inhibitor binds covalently to the enzyme
E. Increasing the concentration of substrate can reverse the changes
Correct Answer: D. Inhibitor binds covalently to the enzyme
Explanation:
Competitive inhibitors do not bind covalently to the enzyme; instead, they bind reversibly to the active site, competing with the substrate. Key characteristics of competitive inhibition include:
• Vmax remains the same because the inhibition can be overcome by increasing substrate concentration.
• Km increases because a higher substrate concentration is needed to reach half the enzyme’s maximum activity.
• The inhibitor is often a structural analog of the substrate. Thus, statement D is incorrect because the covalent binding is characteristic of irreversible inhibitors, not competitive inhibitors.
14. During extended exercise, muscle tissue actively breaks down glucose via glycolysis to provide energy, while the liver synthesizes glucose via gluconeogenesis to maintain blood glucose levels. Which of the following enzymes involved in these pathways would most likely exhibit Michaelis–Menten kinetics (a hyperbolic curve when plotting substrate concentration versus velocity)?
A. Fructose-1,6-bisphosphatase
B. Hexokinase
C. Lactate dehydrogenase
D. Phosphofructokinase 1
E. Pyruvate kinase
Correct Answer: C. Lactate dehydrogenase
Explanation:
Enzymes that follow Michaelis–Menten kinetics show a hyperbolic relationship between substrate concentration and reaction velocity. This typically applies to non-regulatory enzymes.
• Lactate dehydrogenase (LDH) is a non-regulatory enzyme and catalyzes the reversible conversion of Pyruvate to lactate. It follows Michaelis–Menten kinetics.
• Other options (hexokinase, phosphofructokinase 1, pyruvate kinase, and fructose-1,6-bisphosphatase) are regulatory enzymes and exhibit sigmoidal kinetics, reflecting their allosteric regulation in metabolic pathways.
Thus, LDH is the correct choice as it operates in a straightforward, non-regulatory manner during glycolysis and gluconeogenesis.
15. In what way do non-competitive inhibitors affect the Vmax and Km of an enzymatic reaction?
A. Increase Vmax
B. Decrease Vmax
C. Increase Km
D. Decrease Km
E. Keep Km constant
Correct Answer: B. Decrease Vmax, E. Keep Km constant
Explanation:
Non-competitive inhibitors bind to the enzyme at a site other than the active site, altering the enzyme’s function without competing with the substrate. This affects the reaction as follows:
• Vmax decreases: Because the inhibitor reduces the total number of active enzyme molecules available to catalyze the reaction, the maximum reaction velocity (Vmax) is lowered.
• Km remains constant: Non-competitive inhibitors do not interfere with substrate binding at the active site, so the substrate’s affinity for the enzyme (reflected by Km) is unaffected.
Thus, the correct description of non-competitive inhibition is a decrease in Vmax with no change in Km.
16. Which one of the following enzymes catalyzes substrate-level phosphorylation in the TCA cycle?
A. Malate dehydrogenase
B. Succinate thiokinase
C. Succinate dehydrogenase
D. Alpha-keto dehydrogenase complex
E. Isocitrate dehydrogenase
Correct Answer: B. Succinate thiokinase
Explanation:
Succinate thiokinase (also known as succinyl-CoA synthetase) catalyzes the conversion of succinyl-CoA to succinate, coupled with the generation of GTP (or ATP) in a substrate-level phosphorylation reaction. This is the only step in the TCA cycle where a high-energy phosphate compound is directly synthesized.
• Malate dehydrogenase, succinate dehydrogenase, alpha-keto dehydrogenase complex, and isocitrate dehydrogenase are involved in oxidative reactions, not substrate-level phosphorylation.
17. A 45-year-old man presents with symptoms of diarrhea, dermatitis, and confusion, which are suggestive of pellagra, a condition associated with niacin (vitamin B3) deficiency. Further history reveals a diet predominantly based on maize with little protein intake. The physician suspects insufficient availability of an amino acid that acts as a precursor for niacin synthesis.
Which of the following amino acids is a precursor of niacin (Vitamin B3)?
A. Tyrosine
B. Threonine
C. Tryptophan
D. Phenylalanine
E. Arginine
Correct Answer: C. Tryptophan
Explanation:
Tryptophan is a precursor for the synthesis of niacin (vitamin B3) through the kynurenine pathway. About 60 mg of dietary tryptophan can produce 1 mg of niacin. In the case of diets low in protein or tryptophan (e.g., maize-based diets deficient in tryptophan), niacin deficiency can occur, leading to pellagra, characterized by the “3 Ds”: diarrhea, dermatitis, and dementia. None of the other listed amino acids are involved in niacin synthesis.
18. A 30-year-old woman presents to the clinic with recurrent episodes of sneezing, nasal congestion, and skin itching following exposure to pollen. Laboratory tests reveal elevated levels of histamine, a mediator responsible for allergy and inflammation. The physician explains that this mediator is derived from an amino acid.
Which of the following amino acids is a precursor of this mediator?
A. Histidine
B. Tyrosine
C. Phenylalanine
D. Tryptophan
E. Glutamic acid
Correct Answer: A. Histidine
Explanation:
Histamine, a key mediator in allergic reactions and inflammation, is synthesized from the amino acid histidine. This reaction is catalyzed by the enzyme histidine decarboxylase, which removes the carboxyl group from histidine to produce histamine. Other listed amino acids, such as tyrosine, phenylalanine, tryptophan, and glutamic acid, do not serve as precursors for histamine. Instead, they are involved in the synthesis of other molecules, such as catecholamines (tyrosine) and serotonin (tryptophan).
19. A 25-year-old athlete visits the clinic complaining of muscle fatigue and cramps after intense workouts. Blood tests reveal normal glucose levels but reduced glycogen breakdown in muscle tissue. The physician explains that an essential coenzyme involved in muscle glycogen breakdown is deficient, impairing the activity of glycogen phosphorylase.
Which of the following serves as a coenzyme for the muscle glycogen phosphorylase?
A. NADP⁺
B. NAD⁺
C. Pyridoxal phosphate
D. Tetrahydrofolate
E. Adenosyl cobalamin
Correct Answer: C. Pyridoxal phosphate
Explanation:
Pyridoxal phosphate (PLP), the active form of vitamin B6, acts as a coenzyme for muscle glycogen phosphorylase, which catalyzes the breakdown of glycogen to glucose-1-phosphate. This coenzyme plays a critical role by stabilizing the reaction intermediate and facilitating the enzymatic process. Deficiency in PLP can lead to impaired glycogenolysis, contributing to muscle fatigue and cramps during exercise. The other options (NAD⁺, NADP⁺, tetrahydrofolate, and adenosyl cobalamin) do not function as coenzymes for glycogen phosphorylase.
20. A 5-year-old child is brought to the medical OPD in a comatose state. Laboratory investigations reveal elevated CSF glutamine and blood ammonia levels, suggesting a defect in urea cycle enzymes. In conditions of hyperammonemia, the TCA cycle is suppressed. This suppression is due to the impairment of which of the following conversions?
A. Citrate to Isocitrate
B. Isocitrate to Alpha-ketoglutarate
C. Alpha-ketoglutarate to Succinyl CoA
D. Succinyl CoA to Fumarate
E. Fumarate to Malate
F. Malate to Oxaloacetate
Correct Answer: C. Alpha-ketoglutarate to Succinyl CoA
Explanation:
Hyperammonemia causes the depletion of alpha-ketoglutarate due to its diversion into ammonia detoxification pathways (via glutamate and glutamine synthesis). This disrupts the conversion of alpha-ketoglutarate to succinyl-CoA, a critical step in the TCA cycle catalyzed by the alpha-ketoglutarate dehydrogenase complex. This impairment contributes to TCA cycle suppression, reduced ATP production, and the associated neurological symptoms observed in hyperammonemia.
21. Which of the following conversions in the liver might be a lifesaver for a person surviving without food for eight days?
A. Acetyl-CoA to malonyl-CoA
B. Pyruvate to lactate
C. Glycerol to glycerol 3-phosphate
D. Glycogen to glucose 1-phosphate
E. Pyruvate to acetyl-CoA
Correct Answer: C. Glycerol to glycerol 3-phosphate
Explanation:
During prolonged fasting, glycogen stores are depleted, and the liver relies on gluconeogenesis to maintain blood glucose levels. Glycerol, released from the breakdown of triglycerides in adipose tissue, is converted to glycerol 3-phosphate in the liver by glycerol kinase. This process provides a key substrate for gluconeogenesis, ensuring a continued supply of glucose for essential organs like the brain, making it critical for survival during extended periods without food.
22. During a discussion on gluconeogenesis, the professor asked the students to identify the metabolic ratio that shifts dynamics toward hypoglycemia in a chronic alcoholic. Which of the following ratios is most likely responsible for this state?
A. High ATP/ADP ratio
B. Low ATP/ADP ratio
C. High NADH/NAD⁺ ratio
D. Low NADH/NAD⁺ ratio
E. High NADPH/NADP⁺ ratio
F. Low NADPH/NADP⁺ ratio
Correct Answer: C. High NADH/NAD⁺ ratio
Explanation:
In chronic alcoholism, excessive alcohol metabolism increases the NADH/NAD⁺ ratio in the liver. This high ratio disrupts gluconeogenesis by diverting key intermediates such as Pyruvate and oxaloacetate into pathways like lactate and malate production, respectively. This depletion of gluconeogenic substrates leads to hypoglycemia, especially during fasting.
23. In a 40-year-old patient hospitalized with acute myocardial infarction, what will be the likely status of the following ratios: NADH/NAD⁺ and ATP/ADP?
A. Both high
B. Both low
C. High NADH/NAD⁺, Low ATP/ADP
D. Low NADH/NAD⁺, High ATP/ADP
Correct Answer: C. High NADH/NAD⁺, Low ATP/ADP
Explanation:
During an acute myocardial infarction, ischemia limits oxygen delivery to the affected heart tissue, impairing oxidative phosphorylation in mitochondria. This leads to an accumulation of NADH due to reduced electron transport chain activity, resulting in a high NADH/NAD⁺ ratio. Simultaneously, ATP production decreases due to diminished oxidative phosphorylation, leading to a low ATP/ADP ratio. These metabolic changes contribute to cellular energy deficits and tissue damage.
24. During a biochemistry lecture, the professor presented the case of a patient with biotin deficiency. The students were asked why the reaction catalyzed by pyruvate carboxylase has fewer implications despite the enzyme requiring biotin as a cofactor. The students explained that this might be due to an alternative pathway capable of producing its product. Building on this, the professor posed the following question:
Which of the following compounds can directly compensate for the product normally produced by this enzyme?
A. Succinyl CoA
B. Succinate
C. Malate
D. Acetyl CoA
E. Fumarate
Correct Answer: C. Malate
Explanation:
In pyruvate carboxylase deficiency, the production of oxaloacetate from pyruvate is impaired. However, malate can be converted to oxaloacetate by malate dehydrogenase in the TCA cycle. This alternative pathway helps replenish oxaloacetate for gluconeogenesis and other metabolic functions. Other intermediates like succinate, succinyl CoA, acetyl CoA, and fumarate do not directly convert to oxaloacetate and cannot compensate as effectively.
25. A child accidentally ingested a chemical and presents with a high fever. The chemical affects ATP formation in the electron transport chain. Which of the following could cause similar manifestations?
A. Cyanide
B. Malonate
C. 2,4-Dinitrophenol
D. Rotenone
E. Amobarbital
Correct Answer: C. 2,4-Dinitrophenol
Explanation:
2,4-Dinitrophenol is an uncoupler of oxidative phosphorylation. It dissipates the proton gradient across the mitochondrial membrane, preventing ATP synthesis while allowing electron transport to continue. This process releases energy as heat, causing hyperthermia (high fever), similar to the symptoms described. Other compounds, like cyanide and rotenone, inhibit specific components of the electron transport chain but do not cause the same hyperthermic response.
