Insulin is a hormone made up of two distinct peptide chains called the A chain and the B chain, which are connected by disulfide bonds formed between sulfur atoms of cysteine residues. The **A chain contains 21 amino acids**, and the **B chain contains 30 amino acids**, making the entire insulin molecule a protein of 51 amino acids in total. These two chains are derived from a larger precursor molecule called proinsulin, which initially consists of 74 amino acids. Proinsulin undergoes enzymatic cleavage to remove a connecting segment known as the C-peptide, leaving the A and B chains linked together to form active insulin.
The **peptide sequence of the A chain** is:
**Gly-Ile-Val-Glu-Gln-Cys-Cys-Thr-Ser-Ile-Cys-Ser-Leu-Tyr-Gln-Leu-Glu-Asn-Tyr-Cys-Asn**
This sequence includes two cysteine residues that form disulfide bonds with cysteines on the B chain, stabilizing the insulin structure.
The **peptide sequence of the B chain** is:
**Phe-Val-Asn-Gln-His-Leu-Cys-Gly-Ser-His-Leu-Val-Glu-Ala-Leu-Tyr-Leu-Val-Cys-Gly-Glu-Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Thr**
Within this sequence, cysteine residues form disulfide bridges with the A chain cysteines, creating a three-dimensional structure essential for insulin’s biological activity.
These two chains are linked by **two interchain disulfide bonds**, and the A chain also contains an **intrachain disulfide bond** between two of its cysteine residues, which helps maintain its folded shape.
The primary structure—the exact order of amino acids in these chains—is critical because it determines how insulin folds into its functional three-dimensional shape. This folding allows insulin to bind to its receptor on cell surfaces, triggering the regulation of glucose metabolism in the body.
To summarize the peptide sequences clearly:
| Chain | Number of Amino Acids | Peptide Sequence (Single-letter code) |
|——-|———————–|————————————————————|
| A | 21 | G I V E Q C C T S I C S L Y Q L E N Y C N |
| B | 30 | F V N Q H L C G S H L V E A L Y L V C G E R G F F Y T P K T |
The insulin molecule’s structure is highly conserved across species, with minor variations in amino acid sequences in animals like bovines or porcines, but the human insulin sequence is the standard for therapeutic use.
Insulin is synthesized in the pancreas as proinsulin, which folds and forms the correct disulfide bonds before the C-peptide is removed, leaving the mature insulin molecule ready for secretion. This process ensures that insulin is biologically active and capable of regulating blood sugar levels effectively.
Understanding the peptide sequence of insulin is fundamental in biochemistry and medicine, especially for designing insulin analogues used in diabetes treatment. These analogues often involve slight modifications to the amino acid sequence to alter insulin’s absorption, duration, or activity while preserving its core structure and function.
