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
Related conditions
- Primary carnitine deficiency
- Carnitine palmitoyltransferase II (CPT-II) deficiency
- Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
Related
- Carnitine (L-carnitine)
- Carnitine palmitoyltransferase I (CPT-I)
- Malonyl-CoA
- Palmitate (palmitic acid)
- Medium-chain acyl-CoA dehydrogenase (MCAD)
- Acetyl-CoA carboxylase (ACC)
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.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Carnitine shuttle (Reactome, 2026); Carnitine-acylcarnitine translocase deficiency: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); CPT2 gene: MedlinePlus Genetics (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).
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.