• Proteolysis of dietary protein begins in stomach through the action of pepsin, protease, non-specific hydrolysis
• Pepsin - active enzyme

Originally synthesized as an inactive zymogen, pepsinogen

Hydrolyzes proteins in a random, non-specific manner, that is not linked to specific protein sequence

• Pepsinogen - inactive zymogen

zymogen is defined as an inactive substance which is converted into an enzyme when activated by another enzyme

Extra 44 amino acids blocks the active site Must be clipped away -> when it hits the low pH in the stomach -> unfolds (autoproteolysis)

Synthesized and released into stomach

Activated by low pH in the stomach

• Low pH breaks salt bridges to make this extra piece vulnerable to proteolysis
• Extra 44 amino acids become vulnerable to pepsinogen
• Pepsinogen undergoes autoproteolysis
• Benefits of low pH - activation of pepsinogen and denaturation of dietary proteins to random coils, which are more accessible to protease
• pH 7.3 -> pH 2
• Aspartate is protonated

There is aspartate in the active site that are responsible for catalytic activity of pepsin

No longer binds to lysine

• Salt bridge between lysine and aspartate is broken, protein unfolds enough for the inhibitory section of the zymogen to be vulnerable to proteolysis
• Pepsin is a random cleaver - no AA sequence it favors