Correct Answer: C. Hepatic glycogenolysis
At 7 am, approximately 11 hours have elapsed since the 8 pm dinner. During this overnight fasting period, dietary glucose is no longer available, and blood glucose must be maintained through endogenous sources. The liver is the primary organ responsible for glucose homeostasis during fasting. Within the first 8–12 hours of fasting (postabsorptive state), hepatic glycogenolysis is the dominant mechanism. The liver breaks down its stored glycogen (which contains ~100–120 g of glucose equivalents) via the enzyme glycogen phosphorylase, releasing glucose-1-phosphate, which is converted to glucose-6-phosphate and then to free glucose via glucose-6-phosphatase. This free glucose is released into the bloodstream to maintain fasting blood glucose levels (typically 70–100 mg/dL). Gluconeogenesis becomes increasingly important only after 12–24 hours of fasting, when hepatic glycogen stores are depleted. At the 11-hour mark in this scenario, glycogenolysis remains the primary source, making it the most physiologically accurate answer. This is a classic fasting state glucose homeostasis question testing understanding of the temporal sequence of metabolic fuel utilization.
Why the other options are wrong
A. Dietary glucose — This is wrong because 11 hours have elapsed since the last meal (8 pm dinner to 7 am). Dietary glucose is only available during the absorptive state (postprandial period), which typically lasts 3–4 hours after eating. By 7 am, all dietary glucose has been absorbed and the patient is in the postabsorptive (fasting) state, requiring endogenous glucose production. B. Hepatic gluconeogenesis — While gluconeogenesis does occur during fasting, it is NOT the primary source at 11 hours. Gluconeogenesis becomes the dominant glucose source only after hepatic glycogen is depleted (typically after 12–24 hours of fasting). At 11 hours, glycogenolysis is still the major contributor. Choosing this reflects a misunderstanding of the temporal hierarchy of fasting metabolism. D. Muscle glycogenolysis — This is incorrect because muscle glycogen cannot directly contribute to blood glucose. Muscle lacks glucose-6-phosphatase, the enzyme required to convert glucose-6-phosphate to free glucose. Muscle glycogen is used only for muscle's own energy needs via glycolysis. Only the liver can release free glucose into the bloodstream during fasting.
High-Yield Facts
- Hepatic glycogenolysis is the primary glucose source during the first 8–12 hours of fasting; gluconeogenesis becomes dominant only after 12–24 hours.
- Glucose-6-phosphatase is present only in liver and kidney, allowing them to release free glucose; muscle and brain lack this enzyme.
- Fasting blood glucose (70–100 mg/dL) is maintained by hepatic glycogenolysis in the postabsorptive state; failure leads to hypoglycemia.
- Hepatic glycogen stores (100–120 g) are sufficient for 8–12 hours of fasting; prolonged fasting requires gluconeogenesis from lactate, amino acids, and glycerol.
- Postabsorptive state begins 3–4 hours after eating; at 11 hours post-meal, the body is firmly in fasting metabolism.
Mnemonics
FASTING GLUCOSE TIMELINE (Early to Late) 0–8 hrs: Glycogenolysis (liver glycogen abundant) → 8–24 hrs: Gluconeogenesis (glycogen depleting) → >24 hrs: Gluconeogenesis + Ketogenesis (glycogen depleted, protein catabolism). At 11 hours, you're in the glycogenolysis window. G6Pase Location Rule Liver & Kidney = G6Pase present = Release glucose to blood. Muscle & Brain = No G6Pase = Glucose trapped for own use. This is why only liver/kidney can be glucose sources during fasting.
NBE Trap
NBE often pairs "fasting state" with "gluconeogenesis" to trap students who memorize that gluconeogenesis is important during fasting, without understanding that glycogenolysis dominates in the first 12 hours. The temporal distinction is critical.
Clinical Pearl
In Indian clinical practice, understanding this hierarchy is crucial for managing hypoglycemia in fasting patients (common during Ramadan fasting or in malnourished populations). Early fasting hypoglycemia suggests glycogenolysis failure (liver disease, glycogen storage disorders), while late fasting hypoglycemia suggests gluconeogenesis failure (severe malnutrition, critical illness).
_Reference: Guyton & Hall Textbook of Medical Physiology, Ch. 71 (Insulin, Glucagon, and Diabetes Mellitus); Harper's Biochemistry, Ch. 20 (Carbohydrate Metabolism)_