2. Would the pI values of the animal insulins be the same as, greater than, or l

Question

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.

Case 4 The Structure of Insulin Focus concepts The three dimensional structure of insulin is examined and sequences of various animal insulins are compared Prerequisites Amino acid structure . Protein architecture Basic immunology Background Diabetics lack the protein insulin, which is produced by the pancreatic ß-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 irn 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 4.1. A schematic diagram of the structure of insulin is shown in Figure 4.1 Table 4.1: Variation in positions A8, A9, A10, B1, B2, B27 and B30 of insulin. (All other amino acids are the same.) A9 A10 B27 B30 B1 Phe Phe Phe Phe Phe Phe B2 Va ThrThr Val ThrAla Va ThrAla Va ThrAla Va ThrSer Va ThrAla Ala SerAla Ala Species A8 human n Thr er Val Cow pig horse rabbit Thr Ser Thr Gly ir er 0 Thr Ser chicken His Asn Thr duck Glu AsnPro Ala Ser Thr

Explanation / Answer

Human insulin is closest in structure and function with cow or pig insulin and only differs in three amino acids from cow's insulin and one in pig. The pI values is usually similar between human and all other animal insulins except chicken and duck. Since chicken and duck insulin has 7 and 6 amino acid differences respectively with human insulin. The pI of human insulin is approx. 5.4 and that of cow and pig is 5.7 and 6.0 respectively. The chicken insulin is more basic whereas duck insulin is morr acidic.

The immune system has the capability of distinguishing betweem human insulin and animal insulin. Both of their insulins differ from one another in one or more amino acids in the peptide chain. The immune system can spot the difference and produce allergic responses.

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