Energy cost of gluconeogenesis (per glucose synthesized) How many high-energy nucleoside triphosphates are directly consumed in the gluconeogenic pathway to synthesize 1 mole of glucose from 2 moles of pyruvate?

Introduction / Context:
Gluconeogenesis is the anabolic reversal of glycolysis that synthesizes glucose from non-carbohydrate precursors such as lactate, alanine, and glycerol. Because it runs against the thermodynamic grain of glycolysis’s irreversible steps, it consumes high-energy phosphate bonds. Knowing the exact ATP/GTP cost is essential for metabolic accounting and clinical biochemistry.

Given Data / Assumptions:

• Starting point: 2 pyruvate → 1 glucose.
• Bypasses of irreversible glycolytic steps require energetic input.
• NADH requirements are not counted as ATP equivalents here.

Concept / Approach:

The pathway consumes ATP and GTP at key steps: pyruvate carboxylase uses ATP to form oxaloacetate; phosphoenolpyruvate carboxykinase uses GTP to form PEP; two ATP equivalents are also required at 3-phosphoglycerate kinase (twice per glucose). Summing these nucleotide costs yields the total energy investment.

Step-by-Step Solution:

Verification / Alternative check:

Standard biochemistry references agree on the tally: 4 ATP + 2 GTP + 2 NADH per glucose synthesized from pyruvate/lactate sources.

Why Other Options Are Wrong:

Options A, B, and E underestimate the required energy; Option C misallocates nucleotides (3 GTPs not used in the canonical route). Only 4 ATP + 2 GTP matches the pathway stoichiometry.

Common Pitfalls:

Counting NADH as ATP here, or forgetting that each of the duplicated steps occurs twice per glucose (because two 3-carbon molecules are processed).

Final Answer:

4 ATPs and 2 GTPs per glucose