Q.38 Which of the following statements about endogenous synthesis of insulin are
correct?
P. Insulin is synthesized as preproinsulin.
Q. Preproinsulin is converted to proinsulin.
R. Single-site cleavage of proinsulin eliminates C chain.
S. Mature insulin consists of disulphide-linked A and B chains.
(A) P, Q, and R
(B) P, Q, and S
(C) P, R, and S
(D) Q, R, and S
Insulin is synthesized initially as preproinsulin in pancreatic beta cells, which undergoes processing to form mature insulin. The correct statements about its endogenous synthesis are P, Q, and S, making option (B) the right answer for this CSIR NET-style question.
Statement Analysis
P: Insulin is synthesized as preproinsulin.
This holds true as translation of the insulin gene produces preproinsulin, a 110-amino-acid precursor with an N-terminal signal peptide, B chain, C-peptide, and A chain.
Q: Preproinsulin is converted to proinsulin.
Signal peptidase cleaves the signal peptide in the endoplasmic reticulum, yielding proinsulin, which folds with disulfide bonds.
R: Single-site cleavage of proinsulin eliminates C chain.
This is incorrect since two cleavages occur: proprotein convertase 1/3 at the B-C junction and proprotein convertase 2 at the C-A junction, releasing C-peptide.
S: Mature insulin consists of disulphide-linked A and B chains.
Proinsulin processing removes C-peptide, leaving the 21-amino-acid A chain and 30-amino-acid B chain linked by two interchain disulfide bonds.
Option Evaluation
| Option | Statements | Correct? | Reason |
|---|---|---|---|
| (A) P, Q, R | Includes incorrect R | No | R misstates cleavage sites |
| (B) P, Q, S | All accurate steps | Yes | Matches biosynthesis pathway |
| (C) P, R, S | Includes incorrect R | No | R is false |
| (D) Q, R, S | Includes incorrect R | No | R is false |
Insulin biosynthesis represents a key pathway in molecular biology, vital for CSIR NET Life Sciences preparation. Endogenous insulin synthesis begins with preproinsulin translation in pancreatic beta cells, progressing through proinsulin folding and cleavage to yield mature hormone.
Biosynthesis Pathway
Preproinsulin features a signal peptide directing it to the endoplasmic reticulum, where cleavage forms proinsulin with B-C-A chains and disulfide bonds. Proinsulin then moves to the Golgi for packaging into granules.
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Two endoproteases (PC1/3, PC2) execute cleavages at dibasic sites.
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Carboxypeptidase E trims residues post-cleavage.
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Equimolar insulin and C-peptide result.
Common Exam Misconceptions
Many confuse single-site cleavage (false for C-peptide removal) with the actual two-site process. Mature insulin retains A-B linkage via disulfides, excluding C chain.
This pathway underscores protein processing in biotechnology and genetics, aligning with CSIR NET topics like enzyme kinetics and genetic engineering.
