Physiology of metabolism: what is the overall function of gluconeogenesis in human biochemistry under fasting or carbohydrate-restricted states?

Introduction / Context:
Gluconeogenesis synthesizes glucose from non-carbohydrate precursors, sustaining obligate glucose users (e.g., red blood cells, parts of the kidney medulla) when dietary carbohydrate is scarce.

Given Data / Assumptions:

• Physiological settings: fasting, prolonged exercise, low-carbohydrate diet.
• Key substrates: lactate, glycerol, glucogenic amino acids.
• Organs: liver (primary), kidney cortex (significant in prolonged fasting).

Concept / Approach:
Multiple inputs feed gluconeogenesis: lactate via the Cori cycle, glycerol from lipolysis, and amino acids (especially alanine and glutamine) from proteolysis. The goal is to maintain euglycemia when glycogen is depleted.

Step-by-Step Solution:
1) Lactate recycling: lactate → pyruvate → glucose in the liver reduces lactic acidosis risk and supports working muscle (Cori cycle).2) Glycerol usage: glycerol → glycerol-3-phosphate → dihydroxyacetone phosphate enters gluconeogenesis after lipolysis.3) Amino acids: transamination/deamination provide carbon skeletons (e.g., alanine → pyruvate; glutamine → oxaloacetate).4) Outcome: maintain plasma glucose for tissues with limited fatty acid oxidation, such as brain (partially) and RBCs (completely dependent).

Verification / Alternative check:
During overnight fasts, hepatic glycogen supports glucose; as fasting prolongs, gluconeogenesis predominates with renal contribution increasing, consistent with stable glucose levels in healthy adults.

Why Other Options Are Wrong:
Each single statement is true but incomplete; taken together they capture the full function, hence “All of the above.”

Common Pitfalls:
Equating gluconeogenesis with only one substrate (e.g., lactate) or forgetting renal gluconeogenesis during prolonged fasting.

Final Answer:
All of the above