11. During fasting and feeding states, several enzymes are regulated to maintain glucose and energy homeostasis. Specific biochemical processes occur in an individual at rest who has fasted for 12 hours to adapt to the energy demand. Which of the following occurs in such a state?
A. Phosphodiesterase is activated by insulin
B. Pyruvate carboxylase is activated by acetyl-CoA
C. Glycogen synthase is activated by dephosphorylation
D. Phosphorylase is inactivated by dephosphorylation
E. PDH kinase is inhibited by acetyl-CoA
Correct Option: B. Pyruvate carboxylase is activated by acetyl-CoA – During fasting, acetyl-CoA accumulates from fatty acid oxidation and activates pyruvate carboxylase, promoting gluconeogenesis to maintain blood glucose levels.
Incorrect Options:
A. Phosphodiesterase is activated by insulin – Insulin activates phosphodiesterase to degrade cAMP, but this occurs during the fed state, not during fasting.
C. Glycogen synthase is activated by dephosphorylation – Glycogen synthase activation occurs in the fed state, promoting glycogen storage, not during fasting.
D. Phosphorylase is inactivated by dephosphorylation – Phosphorylase is active in fasting (via phosphorylation) to promote glycogen breakdown; it is dephosphorylated and inactivated in the fed state.
E. PDH kinase is inhibited by acetyl CoA – PDH kinase is activated (not inhibited) by acetyl CoA during fasting, suppressing the pyruvate dehydrogenase complex and limiting glucose oxidation.
12. A 35-year-old individual has fasted for 24 hours. At this point, the body shifts primarily to gluconeogenesis to maintain blood glucose levels. Non-carbohydrate sources, such as lactate and glycerol, are utilized to produce glucose. These substrates enter the gluconeogenic pathway through distinct routes but eventually converge at a common intermediate. Which of the following is a common intermediate in the conversion of glycerol and lactate to glucose?
A. Glucose-6-phosphate
B. Malate
C. Oxaloacetate
D. Phosphoenolpyruvate
E. Pyruvate
The correct answer is A. Glucose-6-phosphate: After 24 hours of fasting, the body relies on gluconeogenesis to maintain blood glucose levels. In this process, lactate and glycerol, both non-carbohydrate substrates, are used to produce glucose through distinct entry points into the gluconeogenic pathway.
Lactate Pathway:
Lactate is converted to pyruvate, which then enters the mitochondria and is converted to oxaloacetate.
Oxaloacetate is converted to phosphoenolpyruvate (PEP), which continues through the gluconeogenic pathway, eventually forming glucose-6-phosphate before becoming glucose.
Glycerol Pathway:
Glycerol is phosphorylated to glycerol-3-phosphate, which is then oxidized to dihydroxyacetone phosphate (DHAP).
DHAP enters the gluconeogenic pathway downstream and, through a series of reactions, also leads to glucose-6-phosphate as an intermediate before glucose formation.
Glucose-6-phosphate is the first common intermediate that both pathways share, making it the correct answer.
Incorrect Options:
B. Malate—Malate serves as a shuttle to transport oxaloacetate across the mitochondrial membrane, but it is not the direct convergence point for the lactate and glycerol pathways.
C. Oxaloacetate-Oxaloacetate is generated downstream from pyruvate, so it is not the point at which both pathways meet.
D. Phosphoenolpyruvate – Phosphoenolpyruvate is generated downstream from oxaloacetate, so it is not the first point where both pathways meet.
E. Pyruvate – Although lactate is converted into pyruvate, glycerol bypasses pyruvate and enters the gluconeogenic pathway directly as dihydroxyacetone phosphate, making pyruvate only relevant for the lactate pathway.
13. A 40-year-old individual has been fasting for 36 hours. During this prolonged fasting state, the body relies on fat stores for energy. While even-chain fatty acids only produce acetyl-CoA through beta-oxidation, odd-chain fatty acids produce acetyl-CoA and propionyl-CoA, which can indirectly contribute to gluconeogenesis after further metabolic processing. Through which of the following intermediates does this product enter the gluconeogenesis pathway?
A. α-Ketoglutarate
B. Citrate
C. Fumarate
D. Succinate
E. Succinyl-CoA
Correct Option: E. Succinyl-CoA – The beta-oxidation of odd-chain fatty acids produces propionyl-CoA as one of the final products. Propionyl-CoA undergoes several enzymatic steps, including conversion to methyl-malonyl-CoA and eventually to succinyl-CoA. Succinyl-CoA enters the tricarboxylic acid (TCA) cycle and contributes to gluconeogenesis by generating oxaloacetate, a key precursor in glucose synthesis.
Incorrect Options:
A. α-Ketoglutarate – While α-ketoglutarate is an intermediate in the TCA cycle, it is not directly linked to the metabolism of odd-chain fatty acids. It does not play a role in gluconeogenesis from these fatty acids.
B. Citrate – Citrate is involved in shuttling acetyl-CoA out of the mitochondria for fatty acid synthesis under fed conditions but is not part of the pathway through which odd-chain fatty acids enter gluconeogenesis.
C. Fumarate – Fumarate is another intermediate of the TCA cycle, but it is not produced from the breakdown of odd-chain fatty acids.
D. Succinate – While succinate is part of the TCA cycle, it is not directly formed from odd-chain fatty acid metabolism. Instead, succinyl-CoA is the molecule that links odd-chain fatty acid metabolism to gluconeogenesis.
14. A 15-year-old female presents to the emergency unit in a semi-conscious state after excessive alcohol consumption on a background of poor dietary intake. The lab findings include hypoglycemia, lactic acidemia, and ketosis. This clinical picture suggests that her alcohol intake has disrupted normal metabolic processes, leading to metabolic imbalances. What is the most likely cause of the alcohol-induced metabolic alterations in this patient?
A. High insulin ratio
B. High NADH/NAD⁺ ratio
C. Impaired glycolysis
D. Increased lipogenesis
E. Reduced ketolysis
Correct Option:
B. High NADH/NAD⁺ ratio – Alcohol metabolism increases the levels of NADH by converting ethanol to acetaldehyde and acetaldehyde to acetate, using NAD⁺ as a cofactor in both steps. The elevated NADH/NAD⁺ ratio inhibits key metabolic pathways such as gluconeogenesis (causing hypoglycemia) and pyruvate oxidation (leading to lactic acidosis). This imbalance also promotes the formation of ketone bodies, contributing to ketosis.
Incorrect Options:
A. High insulin ratio – This ratio is typically low during fasting or in hypoglycemia. Alcohol also suppresses insulin secretion, so this is not the correct answer.
C. Impaired glycolysis – Glycolysis is not directly impaired by alcohol consumption. Instead, alcohol metabolism diverts pyruvate toward lactate due to the high NADH levels, affecting gluconeogenesis more than glycolysis.
D. Increased lipogenesis – While chronic alcohol consumption can promote fat accumulation in the liver, acute alcohol intoxication does not significantly increase lipogenesis.
E. Reduced ketolysis – Ketolysis is not the main issue here; rather, ketosis results from increased ketone production due to impaired gluconeogenesis and increased fat metabolism during fasting.
15. A 25-year-old marathon runner is experiencing hypoglycemia after prolonged physical activity. Which of the following substrates will help restore his blood glucose homeostasis?
A. Alanine
B. Glycerol
C. Glycine
D. Lactate
E. Citrate
Correct Option:
A. Alanine – Alanine is a key gluconeogenic amino acid. During prolonged exercise, muscles break down proteins, releasing alanine into the bloodstream. Alanine is transported to the liver, where it is converted into pyruvate and enters the gluconeogenesis pathway, helping restore blood glucose levels.
Incorrect Options:
B. Glycerol – Glycerol, derived from fat breakdown, is a gluconeogenic substrate, but it plays a secondary role compared to amino acids like alanine during intense exercise. It becomes significant during prolonged fasting, not necessarily during immediate post-exercise hypoglycemia.
C. Glycine – Glycine is an amino acid, but it is not a major gluconeogenic substrate. Its contribution to gluconeogenesis is minimal compared to alanine.
D. Lactate – While lactate is a gluconeogenic substrate, it primarily comes from anaerobic glycolysis. For a marathon runner, lactate levels would typically drop after the race when aerobic metabolism predominates, limiting its availability for gluconeogenesis.
E. Citrate –Citrate is an intermediate of the TCA cycle but is not a gluconeogenic substrate.
16. A premature baby delivered due to a maternal hypertensive crisis develops hypoglycemia soon after birth. As the newborn’s metabolism must quickly shift to gluconeogenesis, the availability of key substrates becomes essential. A deficiency in which of the following substrates might best explain the cause of the hypoglycemia?
A. Palmitate
B. Glutamine
C. Glycerol
D. Malate
E. Propionate
Correct Option:
C. Glycerol – In newborns, glycerol is a key substrate for gluconeogenesis. It is derived from the breakdown of triglycerides stored in adipose tissue. However, premature infants have limited adipose stores, leading to insufficient glycerol availability. This deficiency compromises gluconeogenesis, contributing to hypoglycemia soon after birth.
Incorrect Options:
A. Palmitate – Palmitate is a long-chain fatty acid used for energy production via beta-oxidation, but it does not directly contribute to gluconeogenesis. It helps generate acetyl-CoA, which does not feed into glucose production.
B. Glutamine – Although glutamine is involved in several metabolic processes, including the TCA cycle and nitrogen metabolism, it is not a major substrate for gluconeogenesis in the immediate postnatal period.
D. Malate – Malate is an intermediate in the TCA cycle and plays a role in shuttling oxaloacetate across mitochondrial membranes. While it is involved in gluconeogenesis, the availability of glycerol is more critical during neonatal glucose production.
E. Propionate – Propionate, derived from the metabolism of odd-chain fatty acids, contributes to gluconeogenesis via conversion to succinyl-CoA. However, it is a minor gluconeogenic substrate compared to glycerol, especially in the neonatal period.
17. A 16-year-old girl is brought to the emergency department. She was found unconscious by her mother. According to reports, she had been practicing intensely for a dance show and had not eaten for 18 hours prior to the incident. Which of the following sets correctly indicates the activity of key metabolic enzymes in this fasting state?
Correct Answer: E: During prolonged fasting, the body adapts by suppressing glycolysis and enhancing gluconeogenesis to maintain glucose levels. In the given scenario, the activities of PFK-2 and PFK-1 decrease, while fructose-1,6-bisphosphatase and pyruvate carboxylase are upregulated to drive gluconeogenesis. Additionally, the PDH complex is downregulated to prevent pyruvate from being diverted into the TCA cycle, conserving it for glucose production.
Incorrect Options:
Set A, B, C, and D – These sets either incorrectly show increased glycolytic enzyme activity or reduced gluconeogenic enzyme activity, which would not align with the metabolic adaptations expected after 18 hours of fasting.
18. An alcoholic has been binge drinking for two weeks with inadequate food intake. As a result, the individual has become severely hypoglycemic. Chronic alcohol consumption disrupts multiple metabolic pathways, making it difficult for the body to maintain blood glucose levels. Which additional condition might also develop in response to severe hypoglycemia?
A. Increased gluconeogenesis
B. Increased glycogenesis
C. Hypouricemia
D. Lactic acidosis
E. Increased fatty acid oxidation
Correct Option: D. Lactic acidosis
Alcohol metabolism generates excess NADH, which shifts the metabolic balance. Pyruvate is converted to lactate rather than entering gluconeogenesis, resulting in lactic acidosis. The high NADH/NAD⁺ ratio also inhibits gluconeogenesis, worsening hypoglycemia.
Incorrect Options:
A. Increased gluconeogenesis – This is incorrect because excess NADH inhibits gluconeogenesis by limiting the conversion of lactate and pyruvate into glucose precursors, contributing to hypoglycemia rather than reversing it.
B. Increased glycogenesis – In fasting or hypoglycemic states, the body prioritizes glycogenolysis (breaking down glycogen) to raise blood glucose, not glycogenesis (the synthesis of glycogen). Glycogenesis is suppressed during periods of starvation and hypoglycemia.
C. Hypouricemia – This is incorrect. Alcohol metabolism often leads to hyperuricemia due to increased lactate production, which competes with uric acid for excretion in the kidneys.
E. Increased fatty acid oxidation – Although fatty acid oxidation increases during fasting to provide energy, NADH accumulation from alcohol metabolism disrupts normal fat oxidation, leading to fat accumulation rather than increased oxidation.
19. A sprinter is preparing for a competitive sprint. During such intense, short-duration exercise, the body relies heavily on glycolysis for rapid ATP production to meet energy demands. Some metabolic enzymes are activated to maximize energy production, while others are inhibited to redirect resources toward pathways supporting high-intensity effort. Which of the following enzymes is most likely inhibited in the muscle cells of the sprinter during the sprint?
A. Fructose-1,6-bisphosphatase
B. Glucose-6-phosphatase
C. Pyruvate dehydrogenase complex
D. Phosphofructokinase-1 (PFK-1)
E. Lactate dehydrogenase
Correct Option:
A. Fructose-1,6-bisphosphatase – This enzyme is a key regulator of gluconeogenesis, the process that generates glucose from non-carbohydrate sources. During intense exercise, the body focuses on glycolysis, not gluconeogenesis, to produce ATP quickly. Therefore, fructose-1,6-bisphosphatase is inhibited to ensure that energy is directed toward glycolysis, allowing for rapid energy production in muscle cells.
Incorrect Options:
B. Glucose-6-phosphatase – This enzyme is involved in gluconeogenesis and glycogenolysis in the liver but is not active in skeletal muscle. Muscle cells lack this enzyme, making it irrelevant to the muscle’s energy metabolism during the sprint.
C. Pyruvate Dehydrogenase Complex – This complex converts pyruvate into acetyl-CoA for entry into the TCA cycle. Although the TCA cycle supports endurance activities, it is still active during a sprint to some extent. However, the immediate energy needs of the sprint are primarily met through glycolysis, so this enzyme is not strongly inhibited during the sprint.
D. Phosphofructokinase-1 (PFK-1) – PFK-1 is a key enzyme in glycolysis and is highly active during intense exercise like sprinting. Inhibiting PFK-1 would impair ATP production, making it unlikely to be inhibited during the sprint.
E. Lactate Dehydrogenase – This enzyme converts pyruvate into lactate under anaerobic conditions. During a sprint, lactate production increases due to high glycolytic activity, so this enzyme remains active, not inhibited.
20. Which of the following enzymes is activated by the product of beta-oxidation of even-chain fatty acids?
A. Fructose-1,6-bisphosphatase
B. Pyruvate carboxylase
C. Pyruvate dehydrogenase complex
D. Phosphofructokinase-1 (PFK-1)
E. Lactate dehydrogenase
Correct Answer: B. Pyruvate Carboxylase. Acetyl-CoA, the product of beta-oxidation, is a key activator of pyruvate carboxylase. Pyruvate carboxylase catalyzes the conversion of pyruvate to oxaloacetate in the mitochondria, which is crucial for replenishing the TCA cycle and promoting gluconeogenesis. This ensures that oxaloacetate is available to maintain glucose production during fasting or low-carbohydrate states when fatty acid oxidation is active.
Incorrect Options:
A. Fructose-1,6-bisphosphatase – This enzyme is involved in gluconeogenesis, but it is not directly activated by acetyl-CoA. Its activity is regulated by other factors, such as the levels of fructose-2,6-bisphosphate and energy status.
C. Pyruvate Dehydrogenase Complex – Acetyl-CoA inhibits the pyruvate dehydrogenase complex to prevent pyruvate from being converted into more acetyl-CoA, thus redirecting pyruvate toward gluconeogenesis instead.
D. Phosphofructokinase-1 (PFK-1) – PFK-1 is a key enzyme in glycolysis, but its activity is inhibited by high levels of ATP and citrate, which accumulate during fatty acid oxidation. It is not activated by acetyl-CoA.
E. Lactate Dehydrogenase – This enzyme converts pyruvate to lactate under anaerobic conditions. It is not regulated by acetyl-CoA and plays no direct role in fatty acid metabolism.
21. A 25-year-old female fell unconscious at a cocktail party. She had been avoiding meals to fit into a tight gown and collapsed shortly after consuming her first glass of wine. Which of the following metabolic processes is most likely occurring in this individual in this state?
A. Hexokinase is inhibited by glucose 6-phosphate
B. PFK-1 is activated by fructose 2,6-bisphosphate
C. PFK-2 is activated by insulin
D. Pyruvate kinase is activated by fructose 1,6-bisphosphate
E. Pyruvate kinase is phosphorylated in the liver
Correct Answer: E. Pyruvate kinase is phosphorylated in the liver. In a fasted state, the body relies on gluconeogenesis to maintain blood glucose levels, and glycolysis is suppressed in the liver. Glucagon levels rise, leading to the phosphorylation and inhibition of pyruvate kinase in the liver. This inhibition conserves pyruvate for gluconeogenesis rather than its conversion to acetyl-CoA for energy production. Alcohol consumption increases NADH levels, further suppressing gluconeogenesis and exacerbating hypoglycemia.
Incorrect Options:
A. Hexokinase is inhibited by glucose 6-phosphate – This inhibition does occur in cells with adequate glucose levels, but it is not the key regulatory response to fasting and alcohol-induced hypoglycemia.
B. PFK-1 is activated by fructose 2,6-bisphosphate – Fructose-2,6-bisphosphate activates PFK-1, promoting glycolysis. However, in the fasting state with elevated glucagon levels, fructose-2,6-bisphosphate is low, and PFK-1 is inhibited, suppressing glycolysis to prioritize glucose conservation.
C. PFK-2 is activated by insulin – Insulin activates PFK-2, increasing fructose-2,6-bisphosphate and promoting glycolysis. However, in this case, fasting and glucagon dominance would inhibit PFK-2, reducing fructose-2,6-bisphosphate levels.
D. Pyruvate kinase is activated by fructose 1,6-bisphosphate – While fructose-1,6-bisphosphate normally activates pyruvate kinase, glucagon-mediated phosphorylation inhibits pyruvate kinase during fasting, thus reducing glycolysis.
