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Foundation Sciences · Biochemistry

Gluconeogenesis

⏱️ 45–60 minutes read 📖 Biochemistry

Hepatic (and renal) synthesis of glucose from lactate, glycerol and glucogenic amino acids during fasting; reciprocally regulated with glycolysis via PFK-2/F2,6BP.

📌 Learning Objectives

  • Describe the key principles of gluconeogenesis.
  • Explain the clinical relevance of gluconeogenesis.
  • Recognise common conditions linked to gluconeogenesis in MLA-style scenarios.

📋 Overview

Hepatic (and renal) synthesis of glucose from lactate, glycerol and glucogenic amino acids during fasting; reciprocally regulated with glycolysis via PFK-2/F2,6BP. This topic integrates with pathology, pharmacology and clinical medicine and is frequently tested in UK medical school exams and the MLA.

🔬 Basic Science

Hepatic (and renal) synthesis of glucose from lactate, glycerol and glucogenic amino acids during fasting; reciprocally regulated with glycolysis via PFK-2/F2,6BP. Detailed mechanisms, regulation and molecular interactions underpin both normal physiology and disease.

🏥 Clinical Relevance

Failure → fasting hypoglycaemia (von Gierke disease, alcohol-induced hypoglycaemia via NADH excess).

🧪 Investigations

Relevant laboratory tests, imaging or histological examination are used as appropriate to the clinical context.

💊 Management

Management is condition-specific; principles include addressing the underlying biochemical/structural derangement, supportive care and targeted therapy where available.

Revision Resources – expand the sections below for high-yield notes, exam pearls, key facts and further reading.

🎯 MLA High-Yield Notes & Quick Revision ⌄
High-yield topic for the UK MLA — frequently appears in SBA questions linking biochemistry concepts to clinical presentations and management decisions.
Applying biomedical science to clinical practice Diagnosis and investigation Pathophysiology of common conditions
  • Hepatic (and renal) synthesis of glucose from lactate, glycerol and glucogenic amino acids during fasting
  • reciprocally regulated with glycolysis via PFK-2/F2,6BP.
⭐ Exam Pearls ⌄
⭐ High Yield
Key enzymes: pyruvate carboxylase, PEPCK, F1,6-bisphosphatase, glucose-6-phosphatase
Occurs mainly in liver, ~10% kidney cortex
Substrates: lactate (Cori cycle), alanine (Cahill), glycerol
Glucagon ↑ / insulin ↓
💡 Clinical Pearl
: Failure → fasting hypoglycaemia (von Gierke disease, alcohol-induced hypoglycaemia via NADH excess).
⚠️ Exam Tip — Common Mistakes
Confusing gluconeogenesis with related but distinct mechanisms.
Memorising pathways without linking to clinical disease.
🔑 Key Facts ⌄
Key enzymes: pyruvate carboxylase, PEPCK, F1,6-bisphosphatase, glucose-6-phosphatase
Occurs mainly in liver, ~10% kidney cortex
Substrates: lactate (Cori cycle), alanine (Cahill), glycerol
Glucagon ↑ / insulin ↓
Metformin inhibits hepatic gluconeogenesis
📚 References ⌄
  1. BMJ Best Practice
  2. Robbins Basic Pathology
  3. Lippincott Illustrated Reviews: Biochemistry
  4. Wheater's Functional Histology
  5. NICE guidance where applicable.

Further Resources

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