[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Phosphoenolpyruvate carboxykinase (PEPCK)

[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# Phosphoenolpyruvate carboxykinase (PEPCK)

PEPCK turns oxaloacetate into phosphoenolpyruvate using GTP; it is a key gluconeogenic enzyme switched on by glucagon and off by insulin.

Updated 2026-11-01

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## Key facts

- Oxaloacetate + GTP → phosphoenolpyruvate + GDP + CO₂.
- Together with pyruvate carboxylase it goes around the irreversible pyruvate kinase step; the pair costs 2 high-energy bonds per pyruvate.
- It is regulated by the amount of enzyme (transcription), not allosterically: glucagon (cAMP) and cortisol induce it; insulin represses it.
- There is a cytosolic form (PCK1, the main one in the liver) and a mitochondrial form (PCK2).

**EC number**
[4.1.1.32](https://www.enzyme-database.org/query.php?ec=4.1.1.32)

**Genes**
PCK1, PCK2

**Structure (PDB)**
[1KHF](https://www.rcsb.org/structure/1KHF)

## Regulation

- Induction: glucagon, adrenaline, cortisol and thyroid hormone.
- Repression: insulin.

## Inhibitors and toxins

- 3-Mercaptopicolinate (experimental)

## Clinical notes

- In adipose tissue PEPCK serves glyceroneogenesis: it forms glycerol 3-phosphate to re-esterify fatty acids.
- Excess glucocorticoids (Cushing syndrome or long-term therapy) increase PEPCK and blood glucose.
- Cytosolic PEPCK deficiency is very rare and causes fasting hypoglycaemia.

## Pathways

- [Gluconeogenesis](https://durgical.com/en/biochemistry/pathways/gluconeogenesis/)

## Related conditions

- [Cushing syndrome](https://durgical.com/en/conditions/cushing-syndrome/)
- [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/)

## Related

- [Pyruvate carboxylase](https://durgical.com/en/biochemistry/enzymes/pyruvate-carboxylase/)
- [Pyruvate](https://durgical.com/en/biochemistry/molecules/pyruvate/)
- [Fructose-1,6-bisphosphatase (FBPase-1)](https://durgical.com/en/biochemistry/enzymes/fructose-1-6-bisphosphatase/)
- [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/)

## Test yourself

Think of the answer, then tap the question to see it.

## Which nucleotide does PEPCK use as its phosphate source?

GTP; that is why gluconeogenesis spends 2 GTP per glucose.

## How does insulin regulate PEPCK?

It represses PCK1 gene transcription and lowers the amount of enzyme.

## Why does excess cortisol raise blood glucose?

Among other effects it induces PEPCK and glucose-6-phosphatase and increases hepatic gluconeogenesis.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [PCK1: Phosphoenolpyruvate carboxykinase, cytosolic [GTP] (human)](https://www.uniprot.org/uniprotkb/P35558/entry) (UniProt, 2026); [1KHF: PEPCK complex with PEP](https://www.rcsb.org/structure/1KHF) (RCSB Protein Data Bank, 2026); [Gluconeogenesis](https://reactome.org/PathwayBrowser/#/R-HSA-70263) (Reactome, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/biochemistry/enzymes/phosphoenolpyruvate-carboxykinase/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/phosphoenolpyruvate-carboxykinase/