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

# UCP1 (thermogenin)

UCP1 is a proton channel in brown fat: it lets the gradient discharge without making ATP, so the energy leaves as heat.

Updated 2026-11-01

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## Key facts

- It sits in the inner mitochondrial membrane of brown adipose tissue, plentiful in newborns (between the shoulder blades, neck, around the kidneys).
- Cold activates the sympathetic pathway: noradrenaline → β₃ receptor → lipolysis; the released fatty acids open UCP1.
- Cytosolic purine nucleotides (ATP, ADP, GDP) keep it closed.
- It is the basis of non-shivering thermogenesis in the newborn.

**Also called**
Uncoupling protein 1, Thermogenin

**Genes**
UCP1

**Structure (PDB)**
[8J1N](https://www.rcsb.org/structure/8J1N)

## Regulation

- Activators: long-chain fatty acids released by noradrenaline-driven lipolysis.
- Inhibitors: purine nucleotides; chronic cold raises its expression (and “beige” fat).

## Inhibitors and toxins

- ATP, ADP, GTP and GDP (physiological)

## Clinical notes

- Preterm babies have little brown fat and lose heat easily; the incubator makes up for what UCP1 cannot produce.
- On FDG-PET, cold-activated brown fat takes up glucose in the neck and supraclavicular area and can mimic lesions.
- 2,4-Dinitrophenol imitates its effect without control (structure 8J1N shows it bound to UCP1).

## Pathways

- [Electron transport chain and oxidative phosphorylation](https://durgical.com/en/biochemistry/pathways/electron-transport-chain-and-oxidative-phosphorylation/)

## Related conditions

- [Obesity](https://durgical.com/en/conditions/obesity/)

## Related

- [Uncouplers of oxidative phosphorylation](https://durgical.com/en/biochemistry/topics/uncouplers-of-oxidative-phosphorylation/)
- [Chemiosmosis and the proton gradient](https://durgical.com/en/biochemistry/topics/chemiosmosis-and-the-proton-gradient/)
- [ATP synthase (complex V)](https://durgical.com/en/biochemistry/enzymes/atp-synthase/)

## Test yourself

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

## What does UCP1 do with the proton gradient?

It discharges it by returning H⁺ to the matrix without passing through ATP synthase: the energy is released as heat.

## Which adrenergic receptor activates thermogenesis in brown fat?

β₃; noradrenaline triggers lipolysis and the fatty acids open UCP1.

## Which molecules keep UCP1 closed?

Cytosolic purine nucleotides such as ATP and GDP.

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

Sources: [UCP1: Mitochondrial brown fat uncoupling protein 1 (human)](https://www.uniprot.org/uniprotkb/P25874/entry) (UniProt, 2026); [8J1N: Structure of human UCP1 in the DNP-bound state](https://www.rcsb.org/structure/8J1N) (RCSB Protein Data Bank, 2026); [Mitochondrial Uncoupling](https://reactome.org/PathwayBrowser/#/R-HSA-166187) (Reactome, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/biochemistry/enzymes/ucp1/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/ucp1/