Proinsulin
Single-chain precursor of insulin containing A chain, B chain, and connecting C-peptide, cleaved to release mature insulin.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C400H612N106O117S6 |
| Molecular Weight | 9389 Da |
| CAS Number | 9035-68-1 |
| Peptide Class | Prohormone (86 amino acids) |
| Processing | PC1/3 and PC2 cleavage |
Structure
Proinsulin is the 86-amino acid single-chain precursor of insulin, consisting of the B chain (30 aa), connecting peptide (C-peptide, 31 aa), and A chain (21 aa). It folds in the endoplasmic reticulum with three disulfide bonds (two interchain, one intrachain A chain), then is processed in secretory granules.
Mechanism of Action
Proinsulin has ~5-10% of insulin’s biological activity due to reduced receptor binding. In the Golgi, prohormone convertases PC1/3 and PC2 cleave at dibasic residues (Arg-Arg and Lys-Arg), releasing C-peptide and mature insulin. Equimolar amounts of insulin and C-peptide are stored in secretory granules.
Clinical Applications
- Insulin biosynthesis marker: Elevated proinsulin indicates beta-cell stress
- Type 2 diabetes: Disproportionate proinsulin secretion (processing defect)
- Insulinoma: Elevated proinsulin-to-insulin ratio
- Proinsulin intermediates: Des-31,32 and des-64,65 forms as biomarkers
Pharmacology
- Activity: 5-10% of insulin receptor binding
- Half-life: 17-20 minutes (longer than insulin)
- Processing: Sequential cleavage by PC1/3 then PC2
- Secretion: 3-5% of secreted proinsulin is unprocessed
References
- Steiner, D.F. (1978). On the role of the proinsulin C-peptide. Diabetes, 27, 145-148.
- Rhodes, C.J. (2005). Processing of the insulin molecule. Diabetes, 54, S1-S6.
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