BIO ALGEBRA OF LIVING ORGANISMS

(Bio Mathematical Lab of Sikander Aqeel) 

CHAPTER [3] PROTEINS  

Proteins  

THE PRIMARY STRUCTURE OF INSULIN

A study of the primary structure of the protein hormone insulin elucidates chemical events that occur in the biosynthesis of insulin from precursor forms in the pancreatic islet cells, Insulin is initially produced in a form known as preproinsulin, which is converted to an intermediate size protein proinsulin, in the endoplasmic reticulum by an enzyme-catalyzed hydrolysis of the NH3-terminal 23 amino acids in the preproinsulin, 

The polypeptide NH2-terminal fragment is apparently necessary to facilitate membarne during its biosynthesis, the proinsulin molecule is then a substrate for a second enzyme which catalyzes the hydrolysis of two intrachain peptide bonds in proinsulin, resulting in the cleavage of a 30 amino acids segment from within the polypeptide chain, the active insulin product of these proteolytic hydrolysis consists of two small polypeptide chain that are covalently held together by cystine disulfide bonds,   

AMINO ACIDS SEQUENCE OF HUMAN INSULIN (12/21/2016)     

The primary structure of proinsulin contain from 78 (dog) to 86 amino acids, (Human, horse, rat) synthesis of the primary structure of proinsulin is followed by the folding of polypeptide chain into its native three-dimensional structure with formation of its three-dimension disulfide (Cystine) bonds, these disulfide bonds are the same as those shown in the primary structure of its product protein, in which two of these cystine bonds become inter chain bonds, whereas in pro-insulin they were inter chain bonds,  

SEQUENCE OF HUMAN INSULIN 

Variation in positions A8, A9, A10, and B30 of Insulin 

1 = COOH-terminal = 45.25 mole = all A position 

2 = NH2-terminal = 16.5 mole = B end position  

3 = Human = A = (Thr 121.25 m/g) (Ser 106.75) (Ile 134.25) and B = (Thr 121.25) 

A8 POSITIONS OF AMINO ACIDS

  = a2 / b2 = c2 

  = a2 (Human Thr) / b2 (COOH-terminal) = c2 

  = a2 (121.25)    / b2 (45.25) = c2   

  = a / b = (14701.5625) / b (2047.5625) = c2 

  = a / b = 7.18 = c2 

  = a / b = 7.18 + 0.82 (hydrolyze) = 8 

  = a / b = A8 Position 

A9 POSITIONS

  = a2 / b2 = c2 

  = a2 (Human Ser) / b2 (COOH-terminal) = c2 

  = a2 (106.75)    / b2 (45.25) = c2   

  = a / b = (11395.5625) / b (2047.5625) = c2 

  = a / b = 5.56 = c2 

  = a / b = 5.56 + 3.44 (H3 hydrolyze) = 9 

  = a / b = A9 Position  

A10 POSITIONS

  = a2 / b2 = c2 

  = a2 (Human Ile) / b2 (COOH-terminal) = c2 

  = a2 (134.25)    / b2 (45.25) = c2   

  = a / b = (18023.0625) / b (2047.5625) = c2 

  = a / b = 8.80 = c2 

  = a / b = 8.80 + 1.2 (H1 hydrolyze) = 10 

  = a / b = A10 Position 

B30 POSITIONS

  = a2 / b2 = c2 

  = a2 (Human Thr) / b2 (NH2-terminal) = c2 

  = a2 (121.25)    / b2 (16.5) = c2   

  = a / b = (14701.5625) / b (272.25) = c2 

  = a / b = 54.00 = c2 

  = a / b = 54.00 - 24 (C2 of helix) = 30  

  = a / b = B30 Position of insulin 

The C-peptide hydrolyzed from the proinsulin molecule is further processed in the pancreatic islet cells by peptides enzymes that act to hydrolyze a dipeptide from the COOH-terminal and a second dipeptide from NH2-terminal ends of the C-peptide, Stoichiometric amount of the modified C-peptide and insulin are secreted into the blood,