Chemical Identity

Property	Value
Name	β-Endorphin
Gene	POMC (chromosome 2p23.3)
Sequence	Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu
Length	31 amino acids
N-terminal	YGGFM (Met-enkephalin sequence)
MW	3465.0 Da
PDB Structures	1JNR (NMR), 2B5R (NMR)

POMC Processing

POMC (241 aa)
    → ACTH (1-39) → α-MSH (1-13) + CLIP (18-39)
    → β-LPH (1-91) → γ-MSH (1-11) + β-endorphin (1-31)
    → β-MSH (1-18) + β-LPH (42-91)

Tissue-Specific Processing

Tissue	Products	Enzymes
Anterior pituitary	ACTH, β-LPH	PC1/3
Intermediate lobe	α-MSH, β-endorphin	PC2
Hypothalamus	β-endorphin, α-MSH	PC2
Immune cells	β-endorphin	PC2

Receptor

Mu-Opioid Receptor (MOR)

• Gene: OPRM1 (chromosome 6q25)
• G-protein: Gαi → ↓cAMP, ↑K⁺ conductance, ↓Ca²⁺ conductance
• Selectivity: β-endorphin has high affinity for MOR (Kd ~0.3 nM)
• Distribution: Brain (periaqueductal gray, thalamus, cortex), spinal cord

Physiological Functions

Analgesia

• β-endorphin is the most potent endogenous analgesic
• Mechanism: Activates MOR in periaqueductal gray (PAG) → descending inhibition
• Duration: ~30-60 minutes (longer than enkephalins)
• “Runner’s high”: Exercise-induced β-endorphin release

Euphoria and Reward

• Euphoric: Produces intense feelings of well-being
• Addiction: β-endorphin release contributes to drug reward
• Placebo analgesia: Expectation → β-endorphin release

Other Functions

• Stress response: Released during acute stress
• Immune modulation: Suppresses immune function
• GI motility: Reduces intestinal motility

Clinical Significance

Opioid Agonists (Mimicking β-endorphin)

Drug	Route	Indication
Morphine	Oral/IV	Severe pain
Fentanyl	IV/transdermal	Severe pain
Oxycodone	Oral	Moderate-severe pain
Methadone	Oral	Opioid maintenance therapy

Naltrexone (Opioid Antagonist)

• Blocks MOR → prevents β-endorphin effects
• Indications: Alcohol dependence, opioid overdose

Manufacturing

• SPPS (Fmoc): Standard solid-phase synthesis
• Purification: RP-HPLC
• Characterization: Mass spectrometry, NMR
• Short t½: Requires modified analogs for clinical use

References

1. Li CH, Chung D. “Primary structure of the β-endorphin.” PNAS 78:7536-7540, 1981. doi:10.1073/pnas.78.12.7536
2. Goldstein A, et al. “β-Endorphin: a new brain peptide with opiate-like activity.” Science 197:1096-1098, 1977.
3. Helmstetter FJ, et al. “β-Endorphin and the central control of pain.” Progress in Brain Research 103:165-175, 1995.
4. Zubieta JK, et al. “Endogenous opioid release after emotional challenge.” Biological Psychiatry 53:116-125, 2003.
5. Bodnar RJ, et al. “β-Endorphin and pain.” Progress in Brain Research 103:221-229, 1995.