Preproinsulin

Ribosomes feed the growing amino acid chain (preproinsulin) directly into the ER where the signal peptide (red) is immediately cleaved off by the signal peptidase (red triangle) to yield proinsulin. This is later processed further to mature and active insulin. Cell components and proteins in this image are not to scale.

Preproinsulin

Preproinsulin represents the primary translational product of the INS gene. Serving as a precursor molecule in the insulin synthesis pathway, it comprises a peptide chain of 110 amino acids in length. Distinctively, preproinsulin is characterized by a signal peptide attached to its N-terminus.

Insulin Synthesis Pathway

The journey from the INS gene product to the biologically active endocrine hormone, insulin, entails several stages. The synthesis begins with the formation of preproinsulin, which subsequently undergoes various transformations to result in the mature insulin hormone.

From Preproinsulin to Proinsulin

Though preproinsulin serves as an initial step in the synthesis process, it remains biologically inactive. The molecule is then processed by signal peptidases, which meticulously remove its signal peptide from the N-terminus. This results in the formation of proinsulin, which is a more direct precursor to insulin.

Proinsulin to Insulin

The proinsulin molecule undergoes a further transformation to yield the bioactive hormone, insulin. This transition requires the removal of the connecting peptide, commonly referred to as the C-peptide.

Cellular Presence and Medicinal Usage

Intriguingly, the presence of preproinsulin within a cell is almost negligible. The reason behind this scarcity is the immediate removal of the signal peptide, a process intrinsically linked with the translocation of the protein into the endoplasmic reticulum (ER). As a result of this swift processing, preproinsulin doesn't get the opportunity to accumulate in significant amounts within the cell.

Moreover, from a medicinal perspective, preproinsulin rarely finds application, particularly when compared to its subsequent forms. Insulin, the mature product, remains a widely utilized therapeutic agent. Similarly, proinsulin, being a stable intermediate within the ER, also holds relevance in the medicinal arena.

See Also

• INS gene
• Endocrine hormones
• Insulin therapy

Preproinsulin Resources
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