During fasting, when glycogen stores have been depleted, the body begins to synthesise glucose from

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Question prompts the metabolic shift that occurs during prolonged fasting when liver glycogen is depleted and the body needs to maintain blood glucose.

Option a: amino acids. In early to mid fasting, gluconeogenesis primarily uses glucogenic substrates, with amino acids (especially alanine and glutamine) supplying carbon skeletons to form glucose. This pathway is well established as a key source of substrates for hepatic glucose production when glycogen is scarce. The amino groups are typically disposed of via urea cycle while carbon skeletons feed gluconeogenesis.

Option b: fatty acids. Fatty acids themselves cannot be converted into pyruvate or oxaloacetate to form glucose in humans. Instead they are oxidized for energy (via acetyl-CoA and the TCA cycle) and generate acetyl-CoA, but this acetyl-CoA cannot be used to generate net glucose. Thus, fatty acids do not contribute directly to gluconeogenesis as substrates for glucose production.

Option c: acetyl-CoA. Although acetyl-CoA enters the TCA cycle and is central to energy production, it cannot serve as a net gluconeogenic substrate to produce glucose in humans because the pyruvate dehydrogenase step makes acetyl-CoA unable to be converted back to phosphoenolpyruvate for gluconeogenesis. Hence, acetyl-CoA cannot be directly used to make glucose.

Option d: ketone bodies. Ketone bodies are produced during prolonged fasting from acetyl-CoA and serve as alternative fuels for tissues like brain and muscle. They are not gluconeogenic substrates themselves; they are an energy source, not a carbon source for hepatic glucose output.

In summary, among the listed options, amino acids are the gluconeogenic substrates that support glucose synthesis during fasting when glycogen is depleted, whereas fatty acids, acetyl-CoA, and ketone bodies do not provide glucose carbon directly.

During fasting, when glycogen stores have been depleted, the body begins to synthesise glucose from

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