Denaturation of proteins

Because of their secondary and tertiary structures, most proteins are resistant to digestive enzymes — few bonds are accessible to the proteolytic enzymes that catalyse hydrolysis of peptide bonds. However, apart from covalent links formed by reaction between the side-chains of lysine and aspartate or glutamate, and disulphide bridges, the native structure of proteins is maintained by relatively weak non-covalent forces: ionic interactions, hydrogen bonding and van der Waals forces.

Like all molecules, proteins vibrate, and as the temperature increases so the vibration increases. Eventually, this vibration disrupts the weak non-covalent forces that hold the protein in its organized structure. When this happens, proteins frequently become insoluble. This is the process of denaturation — a loss of the native structure of the protein. In denatured proteins most of the peptide bonds are accessible to digestive enzymes, and consequently denatured (i.e. cooked) proteins are more readily hydrolysed to their constituent amino acids. Gastric acid is also important, as relatively strong acid will also disrupt hydrogen bonds and denature proteins.


Protein digestion occurs by hydrolysis of the peptide bonds between amino acids. There are two main classes of protein digestive enzymes (proteases), with different specificities for the amino acids forming the peptide bond to be hydrolysed, as shown in Table 4.2:

  • Endopeptidases cleave proteins by hydrolysing peptide bonds between specific amino acids throughout the molecule.
  • Exopeptidases remove amino acids one at a time from either the amino or carboxyl end of the molecule, again by the hydrolysis of the peptide bond.

The first enzymes to act on dietary proteins are the endopeptidases: pepsin in the gastric juice and trypsin, chymotrypsin and elastase secreted by the pancreas into the small intestine. (The different specificities of trypsin, chymotrypsin and elastase are discussed in section 2.2.1.)

The result of the combined action of the endopeptidases is that the large protein molecules are broken down into a number of smaller polypeptides with a large number of amino and carboxy terminals for the exopeptidases to act on. There are two classes of exopeptidase:

  • Carboxypeptidases, secreted in the pancreatic juice, release amino acids from the free carboxyl terminal of peptides.
  • Aminopeptidases, secreted by the intestinal mucosal cells, release amino acids from the amino terminal of peptides.

Table 4.2 Protein digestive enzymes

Secreted by


Endopeptidases Pepsin





Gastric mucosa Adjacent to aromatic amino acid, leucine or methionine

Pancreas Lysine or arginine esters

Pancreas Aromatic esters

Pancreas Neutral aliphatic esters

Intestinal mucosa Trypsinogen ^ trypsin


Carboxypeptidases Aminopeptidases Tripeptidases Dipeptidases

Pancreas Intestinal mucosa Mucosal brush border Mucosal brush border

Carboxy-terminal amino acids Amino-terminal amino acids Tripeptides Dipeptides Activation of zymogens of proteolytic enzymes

The proteases are secreted as inactive precursors (zymogens) — this is essential if they are not to digest themselves and tissue proteins before they are secreted. In each case the active site of the enzyme is masked by a small region of the peptide chain which has to be removed for the enzyme to have activity. This is achieved by hydrolysis of a specific peptide bond in the precursor molecule, releasing the blocking peptide and revealing the active site of the enzyme.

Pepsin is secreted in the gastric juice as pepsinogen, which is activated by the action of gastric acid, and also by the action of already activated pepsin. In the small intestine, trypsinogen, the precursor of trypsin, is activated by the action of a specific enzyme, enteropeptidase (sometimes known by its obsolete name of enterokinase), which is secreted by the duodenal epithelial cells; trypsin can then activate chymotrypsinogen to chymotrypsin, proelastase to elastase, procarboxypeptidase to carboxypeptidase and proaminopeptidase to aminopeptidase. Absorption of the products of protein digestion

The end-product of the action of endopeptidases and exopeptidases is a mixture of free amino acids, di- and tripeptides and oligopeptides, all of which are absorbed: • Free amino acids are absorbed across the intestinal mucosa by sodium-dependent active transport, as occurs in the absorption of glucose and galactose (see Figure 4.9). There are a number of different amino acid transport systems with specificity for the chemical nature of the side-chain (large or small neutral, acidic or basic — see Figure 4.18). Similar group-specific amino acid transporters occur in the renal tubules (for reabsorption of amino acids filtered at the glomerulus) and for uptake of amino acids into tissues. The various amino acids carried by any one transporter compete with each other for absorption and tissue uptake.

  • Dipeptides and tripeptides enter the brush border of the intestinal mucosal cells, where they are hydrolysed to free amino acids, which are then transported into the bloodstream.
  • Relatively large peptides may be absorbed intact, either by uptake into mucosal epithelial cells (the transcellular route) or by passing between epithelial cells (the paracellular route). Many such peptides are large enough to stimulate antibody formation — this is the basis of allergic reactions to foods.

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  • sari
    Does metabolism denature protein?
    1 year ago

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