Introduction to chemistry of proteins

Denaturation of Proteins

Proteins have finite lifetimes. They are also subjected to environmental damages like oxidation, proteolysis, denaturation and other irreversible modifications.

Denaturation involves the destruction of the higher-level structural organization (20, 30 and 40) of protein with the retention of the primary structure by the action of denaturing agents.

A denatured protein loses its native physico-chemical and biological properties since the bonds that stabilize the protein are broken down. 

Thus, the polypeptide chain unfolds itself and remain in solution in the unfolded state. The denatured protein may retain its biological activity by refolding (renaturing) when the denaturing agent is removed.

Factors that Affect Denaturation

Denaturing agents

1. physical factors

Temperature, pressure, mechanical shear force, ultrasonic vibration and ionizing radiation causes the protein to lose its biological activity.

2. Chemical factors

Acids and alkalis, organic solvents (actone, ethanol), detergents (cleaning agents), certain amides urea, guandidine hydrochloride, alkaloids, and heavy metal salts (Hg, Cu, Ba, Zn, Cd…) Cause the denaturation.

 Properties of a Denatured Protein

a). An increase in number of reactive and functional group in the composition of the native protein molecule (side chain group of amino acids, COOH, NH₂, SH, OH … etc).

B. Reduced solubility and pronounced propensity for precipitation this occurs due to loss of the hydration shell and the unfolding of protein molecules with concomitant exposure of hydrophobic radicals and neutralization of charged polar groups.

C. Configurational alteration of the protein molecule.

D. Loss of biological activity evoked by the disarrangement of the native structural molecular organization.

E. Access of proteolytic enzymes in comparison with the native protein 

Clinical Application of Denaturation

The amounts of proteins found in the urine, serum, CSF are utilized to assess various pathological conditions. The appearance of proteins like Albumin and Globulin in the urine can be detected by precipitating them using ammonium sulphate. 

This could be used to asses the degree of kidney impairment and glomerular permeability.

In some disease, abnormal proteins may be present in plasma and be filtered at the glomeruli. The most important member is Bence-jons’ protein which is most often associated with multiple myeloma. 

So, recognition of such protein in the urine may be useful in the diagnosis of the disease.