Gluconeogenesis: Making Glucose When You’re Fasting – MCAT Essentials

What happens when you run out of glucose but still need energy? Your body makes its own through a process called gluconeogenesis. It’s not just a reversed glycolysis—there are unique enzymes, key checkpoints, and regulatory controls the MCAT wants you to understand. Let’s break it down clearly.

🧬 Gluconeogenesis: Where and When?

  • Occurs in: Liver (mostly), kidneys (minor role)

  • Activated during: Fasting, starvation, intense exercise

  • Hormonal trigger: ↑ Glucagon, ↓ Insulin

  • Purpose: Maintain blood glucose for brain/RBCs

🧠 MCAT Tip: Brain and red blood cells rely on glucose. That’s why this pathway matters!

🔄 Glycolysis vs Gluconeogenesis

Feature Glycolysis Gluconeogenesis
Overall direction Glucose → Pyruvate Pyruvate → Glucose
Energy Produces ATP Consumes ATP, GTP, NADH
Key tissue All cells Liver, kidney
Hormonal control Insulin activates Glucagon activates

🔬 Key Enzymes to Know

Step Blocked in Glycolysis Enzyme in Gluconeogenesis Notes
Pyruvate → PEP Pyruvate carboxylase → PEPCK Requires ATP and GTP
Fructose-1,6-bisP → F6P Fructose-1,6-bisphosphatase Major regulation point
G6P → Glucose Glucose-6-phosphatase Final step, only in liver/kidney

🧠 These 3 bypass enzymes are MCAT favorites.

🧪 MCAT Passage Application

Example Question:

“A defect in glucose-6-phosphatase leads to hypoglycemia...”
→ Gluconeogenesis is blocked → glucose can't exit liver

Experimental Setup:

“Cells treated with glucagon increase PEPCK activity...”
→ Indicates active gluconeogenesis in response to fasting signal

🎯 Final MCAT Tips

  • Don’t memorize every step—focus on unique enzymes and regulation

  • Recognize how it’s different from glycolysis (ATP use, tissue, direction)

  • Know when and why the body uses this process (e.g., fasting, hormone cues)

  • Watch for hormonal context: glucagon = think gluconeogenesis

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