Insulin is a hormone that manages the body’s use of glucose. As a protein, it is constructed from amino acids arranged in a specific order, known as the amino acid sequence, which dictates the protein’s structure and function. Understanding this sequence is fundamental to comprehending how insulin works and how its absence or malfunction can impact health.
Decoding Insulin: The Amino Acid Blueprint
Human insulin is a protein composed of 51 amino acids organized into two separate polypeptide chains. The A chain consists of 21 amino acids, and the B chain contains 30. These two chains are connected at two different points by chemical links called disulfide bonds, which form between specific cysteine amino acids.
The structure is stabilized by a third disulfide bond located within the A chain, creating a loop. This network of bonds gives the insulin molecule its specific three-dimensional shape. This shape is directly related to its ability to bind to receptors on cells, and any deviation in the sequence can impair its function.
Unveiling the Code: A Scientific Milestone
Determining insulin’s amino acid sequence was a significant scientific achievement of the 1950s. A team led by biochemist Frederick Sanger took on the challenge, ultimately providing the first definitive proof that proteins have a defined, unchangeable sequence of amino acids.
His team broke the insulin molecule into smaller fragments and developed methods to identify the amino acids at their ends. By analyzing how these pieces overlapped, they reconstructed the full sequence of both the A and B chains.
For this accomplishment, Sanger was awarded the Nobel Prize in Chemistry in 1958. His discovery that a protein has a specific, genetically determined structure opened the door for molecular biology, paving the way for sequencing other proteins and entire genomes.
Insulin Across Species: An Evolutionary Tale
While insulin’s function is conserved across the animal kingdom, its exact amino acid sequence varies. For instance, porcine (pig) insulin differs from human insulin by only a single amino acid in the B chain, while bovine (cow) insulin has three differences.
These small differences reflect evolutionary history, as closely related species have more similar insulin sequences. Before genetic engineering, insulin extracted from the pancreases of pigs and cows was the primary treatment for people with diabetes.
Because animal insulins are so similar to the human version, they function in the human body, though the slight differences could sometimes trigger an immune response. Comparing these sequences provided a source for treatment and offered insights into the molecular relationships between species.
From Sequence to Solution: Medical and Technological Breakthroughs
Knowing the precise amino acid sequence of human insulin was the foundation for developing synthetic “human” insulin. Using recombinant DNA technology, scientists in the late 1970s inserted the human insulin gene into bacteria, turning them into microscopic factories for the hormone.
The resulting product, first marketed in 1982 as Humulin, was identical to insulin from the human body. This eliminated the immune reactions associated with animal insulins and made a safer, more reliable supply available to people with diabetes.
This knowledge also allows researchers to identify mutations in the insulin gene (INS) that cause rare forms of diabetes. By pinpointing how a specific change in the amino acid sequence affects the protein’s structure, scientists can better understand the molecular basis of these diseases and develop new insulin analogs.