Enzymes can be regulated by transfer of a molecule or atom from a donor to an amino acid side chain that serves as the acceptor of the transferred molecule. Another way of regulating an enzyme is by altering the amino acid sequence itself by proteolytic cleavage.
Many enzymes are activated or inactivated by the transfer of inorganic phosphate from ATP to an acceptor—for example, the side‐chain oxygen of serine. The combination of protein phosphorylation by kinases and dephosphorylyation by phosphatases can afford a fine level of control over enzyme activity.
Why doesn't chymotrypsin digest us from the inside out? After all, it can digest many proteins, including our own. One answer is that chymotyrpsin is synthesized in the pancreas as an inactive form, termed chymotrypsinogen,
in which form it is transported to the duodenum (the part of the small intestine, located just after the stomach). These inactive forms of enzymes are called zymogens.
Chymotrypsinogen in the duodenum is converted to chymotrypsin by the related serine protease trypsin, which prefers to cut proteins at the carboxy side of basic amino acids. Two small segments of chymotrypsinogen are removed to make chymotrypsin.
Many proteins are synthesized in an inactive form and are only activated at a particular site in the cell or the body. Besides digestive enzymes, the proteins (called factors) involved in blood clotting circulate in the bloodstream as zymogens. The first proteins in the pathways are activated by trauma or tissue damage. The activated proteins cleave other zymogens to active enzymes, which in turn cleave other factors. Ultimately, the protein fibrinogen is cleaved to fibrin, the protein component of the clot.