[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Carnitine shuttle

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

# Carnitine shuttle

The inner mitochondrial membrane does not let long-chain acyl-CoA through: carnitine carries it across in four steps.

Updated 2026-11-01

## Key facts

- CPT-I (outer membrane) → CACT translocase (inner membrane) → CPT-II (inner face).
- CPT-I is the control point: malonyl-CoA inhibits it.
- Short- and medium-chain fatty acids (under 12 C) do not need the shuttle.
- Shuttle defects cause hypoketotic hypoglycaemia, cardiomyopathy or rhabdomyolysis.

## In detail

- 1. In the cytosol acyl-CoA synthetase activates the fatty acid to acyl-CoA.
- 2. CPT-I swaps CoA for carnitine and forms acylcarnitine in the intermembrane space.
- 3. Carnitine-acylcarnitine translocase (CACT, SLC25A20 gene) brings acylcarnitine in and takes a free carnitine out.
- 4. CPT-II, on the inner face of the inner membrane, puts CoA back: acyl-CoA ready for β-oxidation.
- 5. Free carnitine returns to the cytosol through the same translocase and is reused.
- Diagnosis: on the acylcarnitine profile, CPT-I gives high free carnitine and low long acylcarnitines; CACT and CPT-II give high long acylcarnitines (C16, C18:1).

**Also called**
Carnitine system, Acyl transport into mitochondria

## Clinical notes

- CPT1A deficiency: hypoglycaemia and hepatomegaly in infants; fatty acids without ketones.
- CPT-II deficiency: the adult form gives muscle pain and dark urine (rhabdomyolysis) with prolonged exercise or fasting.
- CACT deficiency: severe in the newborn, with arrhythmias and hyperammonaemia.

## Pathways

- [Fatty acid β-oxidation](https://durgical.com/en/biochemistry/pathways/fatty-acid-oxidation/)

## Related conditions

- [Primary carnitine deficiency](https://durgical.com/en/conditions/primary-carnitine-deficiency/)
- [Carnitine palmitoyltransferase II (CPT-II) deficiency](https://durgical.com/en/conditions/carnitine-palmitoyltransferase-ii-deficiency/)
- [Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency](https://durgical.com/en/conditions/medium-chain-acyl-coa-dehydrogenase-deficiency/)

## Related

- [Carnitine (L-carnitine)](https://durgical.com/en/biochemistry/molecules/carnitine/)
- [Carnitine palmitoyltransferase I (CPT-I)](https://durgical.com/en/biochemistry/enzymes/carnitine-palmitoyltransferase-i/)
- [Malonyl-CoA](https://durgical.com/en/biochemistry/molecules/malonyl-coa/)
- [Palmitate (palmitic acid)](https://durgical.com/en/biochemistry/molecules/palmitate/)
- [Medium-chain acyl-CoA dehydrogenase (MCAD)](https://durgical.com/en/biochemistry/enzymes/medium-chain-acyl-coa-dehydrogenase/)
- [Acetyl-CoA carboxylase (ACC)](https://durgical.com/en/biochemistry/enzymes/acetyl-coa-carboxylase/)

## Test yourself

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

## In what order do the carnitine shuttle proteins act?

CPT-I on the outer membrane, CACT translocase in the inner one and CPT-II on the inner face of the inner membrane.

## Which shuttle step does malonyl-CoA regulate?

CPT-I, the rate-limiting step of long-chain β-oxidation.

## Which fatty acids do not need the carnitine shuttle?

Short- and medium-chain ones, which cross on their own and are activated in the matrix.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/biochemistry/topics/carnitine-shuttle/)

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

Sources: [Carnitine shuttle](https://reactome.org/PathwayBrowser/#/R-HSA-200425) (Reactome, 2026); [Carnitine-acylcarnitine translocase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/carnitine-acylcarnitine-translocase-deficiency/) (MedlinePlus, US National Library of Medicine, 2026); [CPT2 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/cpt2/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

[← All of biochemistry](https://durgical.com/en/biochemistry/)

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

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