Insulin bovine, structure

Fig.l. Insulin. Primary structure of sheep insulin. Human (H) and bovine (B) insulin differ from sheep insulin in the sequence region A8 to 10 in addition, in human insulin, the C-terminal alanine of the B-chain is replaced by threonine. 

The treatment of type 1 diabetes is the subcutaneous injection of insulin, as insulin cannot be administered orally because it would be broken down in the stomach due to the low pH. Initially, animal insulin was used in the treatment of diabetes, since bovine and porcine insulin are structurally similar to human insulin. Nowadays, most of the insulin used in the treatment of diabetes is human insulin produced via recombinant DNA (see Ch. 27). There are a number of insulin formulations available, e.g. short-, intermediate- or long-acting and biphasic (a mixture short- and intermediate-acting insulin), and these are described in more detail in Chapter 27. There is a range of therapy protocols indicated, based on the individual condition of the patient. 

Sanger also determined the sequence of the A chain and identified the cysteine residues involved in disulfide bonds between the A and B chains as well as in the disulfide linkage within the A chain. The complete insulin structure is shown in Figure 27.11. The structure shown is that of bovine insulin (from cattle). The A chains of human insulin and bovine insulin differ in only two amino acid residues then B chains are identical except for the amino acid at the C terminus. 

Mature insulin consists of two polypeptide chains connected by two interchain disulfide linkages. The A-chain contains 21 amino acids, whereas the larger B-chain is composed of 30 residues. Insulins from various species conform to this basic structure, while varying slightly in their amino acid sequence. Porcine insulin (5777 Da) varies from the human form (5807 Da) by a single amino acid, whereas bovine insulin (5733 Da) differs by three residues. 

Fig. 17 (a) Chemical structure of polythiophene poly((3,3"-di[(S)-5-amino-5-carbonyl-3-oxapen-tyl]-[2,2 5 2"])-5-,5"-terthiophenylene hydrochloride), PONT, (b) Emission spectra of 6.5 pM PONT—HC1 (on a chain basis) in 25 mM HC1 (black spectrum), 25 mM HC1 with 5.0 pM of native bovine insulin (blue spectrum), 25 mM HC1 with 5.0 pM fibrillar bovine insulin (red spectrum). The emission spectra were recorded with excitation at 400 nm [31]... 

The significance of Sanger s work is immense. It proved for the first time that the structure of a protein is unique that is, aU molecules of bovine insulin, for example, possess the same sequence of amino acids along the polypeptide chains. This sequence has no obvious order, but it is unique. This singular finding requires that there is a genetic code information encoded in a molecule which specifies the sequence of amino acids in the insulin molecule and, for that matter, in all protein molecules. 

The formation of three disulfide bonds in bovine insulin brings parts of the chain that are distant in terms of amino acid sequence into close proximity in the three-dimensional structure of the protein. 

F ig U re 10.2 The primary structure of bovine insulin. This molecule possesses two polypeptide chains, labeled A and B. These are joined by two disulfide bridges between Cys amino acid residues. There is a third disulfide bridge linking two Cys residues in the A chain. 

Before we take leave of primary structures for proteins, there is one last, important realization. Proteins serving the same function in different species may have different primary structures. For example, the primary structures of bovine, ovine, and human insulins are not quite the same. They are closely related but not identical. Different species have discovered different protein solutions for the same biological problem. 

Insulin is a polypeptide hormone that consists of two peptide chains bonded by two disulfide bonds. The two chains are designated A and B. The A chain consists of 21 amino acids with a third internal disulfide bond, and the chain contains the remaining 30 amino acids. All vertebrates produce insulin and the structure is similar in these species. For example, the insulin produced in humans and porcine species differs by only one amino acid, and humans and bovine insulin differ by three amino acids. Insulin plays a crucial role in several physiological processes. These include the regulation of sugar in the body, fatty acid synthesis, formation of triglycerides, and amino acid synthesis. 

P. D. Walker and P. G. Mezey, Can. /. Chem., 72,2531 (1994)Realistic, Detailed Images of Proteins and Tertiary Structure Elements Ab Initio Quality Electron Density Calculations for Bovine Insulin. 

Wen et al. (1994) investigated the Raman optical activity of poly-L-lysine both as the random coil and the a-helix. They compared these spectra to the spectra of bovine serum albumin and insulin and arrived at the conclusion that tertiary structure of proteins can be readily deduced from the ROA spectra. 

Structures of human proinsulin and insulin. Insulin is derived from proinsulin by cleavage at the dipeptides Arg-Arg and Lys-Arg to give A and B chains held together by disulfide bonds. In the pig, B30 is Ala. In the cow, A8 is Ala, AlO is Val, and B30 is Ala. Bovine and porcine insulins are used extensively in clinical practice. 

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