Case Study 1 The Structure of Insulin
The three dimensional structure of insulin is examined and sequences of various animal insulins are compared.
• • • Amino acid structure Protein architecture Basic immunology
Diabetics lack the protein insulin, which is produced by the pancreatic β-cells of the islets of Langerhans. Insulin stimulates uptake of glucose from the blood into the tissues. Diabetes is treated by replacing the missing insulin. Human insulin is produced industrially by recombinant bacteria, but before this method was available, animal insulin was used instead. Insulin consists of two polypeptide chains, an A chain and a B chain, joined together by disulfide bonds. The smaller of the two chains is referred to as the A chain and is 21 amino acids long in humans. The second chain is referred to as the B chain and is 30 amino acids long in humans. Insulin from various animals is similar to, but not identical to human insulin, as illustrated in Table. A schematic diagram of the structure of insulin is shown in Figure. Table: Variation in positions A8, A9, A10, B1, B2, B27 and B30 of insulin. (All other amino acids are the same.) Species human cow pig horse rabbit dog chicken duck A8 Thr Ala Thr Thr Thr Thr His Glu A9 Ser Ser Ser Gly Ser Ser Asn Asn A10 Ile Val Ile Ile Ile Ile Thr Pro B1 Phe Phe Phe Phe Phe Phe Ala Ala B2 Val Val Val Val Val Val Ala Ala B27 Thr Thr Thr Thr Thr Thr Ser Ser B30 Thr Ala Ala Ala Ser Ala Ala Thr
1. What animals would serve as the best sources of insulin to be used for treating diabetics? Explain your answer. 2. Would the pI values of the animal insulins be the same as, greater than, or less than human insulin?
3. Some people developed allergies to the animal insulin because their immune systems recognized the proteins as foreign. Explain why the immune system would be able to distinguish animal insulin from human insulin. 4. A SDS-PAGE gel is run of proinsulin...
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