Structural Biochemistry/Enzyme/Zymogen

Definition


A zymogen(also denoted as a proenzyme) is a group of proteins that can also be described as an inactive enzyme. Since it is an inactive precursor, it does not hold any catalytic activity. These zymogens can be activated by chemical processes such as cleaving, hydrolysis, along with other biochemical changes that cleave the inactive enzyme to make it active. These biochemical processes often occurs in a lysosome, where cleavage reveals the active site. Exposure of active site allow the enzyme to become active and function to catalyze reactions. The reason for cells to secrete inactive enzymes is to prevent unwanted destruction of cellular proteins. It is only when the conditions are right that zymogens become activated into enzymes. There are specialized zymogenic cells that work only to synthesize and store zymogens in inactive form, ready to send to the parts of the body at need.

Examples
Examples of zymogens include:

Pepsinogen

Pepsinogen, inactive precursor form of pepsin, is secreted by Chief cells in the stomach. Pepsinogen is activated by Hydrochloric acid (secretion from Parietal cells) because Hydrochloric acid provides the necessary acidic environment for which pepsin works best. Once pepsinogen becomes pepsin, it is responsible for the breakdown of food. The difference between pepsinogen and pepsin is that its primary structure has an additional 44 amino acids. The activation of pepsinogen to pepsin makes pepsin available to catalyze pepsinogen further to cleave it into more pepsin.

Trypsinogen

Trypsinogen is the inactive form of trypsin. It is secreted by the pancreas and found in pancreatic juice. Once activated in the duodenum, trypsin cleaves peptide chains at the carboxyl side of the amino acids lysine and arginine unless they are preceding a proline. The importance of trypsin is its ability to cleave other zymogens such as chymotripsinogen and procarboxypeptidase.

Chymotrypsinogen

Once chymotrypsinogen is cleaved by trypsin, and reacted with Chymotrypsin produces a fully active enzyme, Chymotrypsin. Chymotrypsin is found in the digestive system of mammals, as well as other organisms. It works by cleaving peptides at the carboxyl end of aromatic amino acids (Tryptophan, Tyrosin, and Phenylalanine)



Procarboxypeptidase

Procarboxypeptidase, which is the inactive form of carboxypeptidase, is converted to the active form by trypsin and enteropeptidase. It is secreted by the pancreas. Only some forms of carboxypeptidase are initially produced in the inactive form. However, the advantage of this mechanism is to ensure that the enzymes are not immediately exhausted before digestion.

Nuclease

Nuclease is an enzyme which can break phosphodiester bonds between nucleotides in a DNA sequence. Nucleases contain a general range of enzymes such as endonucleases. Nucleases vary in the DNA sequences they cut as certain phosphodiester bonds are cleaved in such a way that may not always completely symmetrical.

Pancreatic amylase

Pancreatic Amylase is an enzyme that converts complex sugars such as starches and polysaccharides of carbohydrates into simpler sugars during digestion. Amylase hydrolyzes starch, glycogen, and dextrin to form in all three instances glucose, maltose, and the limit-dextrins. Amylase is mainly secreted by the salivary glands, but some may also be found in the pancreas that also help aid in digestion.

Lipase

Lipase is the active form of prolipase. Once activated, the water soluble enzyme is the catalyst for the hydrolysis ester bonds in water-insoluble, lipid substrates. This action is what classifies lipases as a subclass of the esterases. It cleaves fats into monoglycerides, fatty acids, and glycerols. The lipase also is essential in the process of digestion, as well as the transport and processing of dietary lipids in almost all organisms.

Proelastase

Proelastease is the inactive form of elastase. The activation of Proelastease is initially done through the simple cleavage of multiple sub-unit residues that bind to the central structure of the protein structure. The cleavage disrupts the hydrophobic interactions of the tertiary structure, allowing the polar regions of the enzyme to respond to digestion. Proleastease is distinct from Chymotrypsin through isolation by chromatography reveals that this structure is highly resistant and further stabilized by internal hydrogen bonding. Activation of proelastase and propeptidase with trypsin changed their electrophoretic mobilities. The activated proelastase migrated at the same rate as authentic, pure elastase.The proenzymes that were originally highly insoluble could be solubilized by treatment with alumina Cγ gel.

Enteropeptidase

Enteropeptidase is produced within the walls of the small intestines secreted by the duodenum glands. This enzyme proteolytically activates trypsinogen to trypsin which simultaneously activates other digestive enzymes as well. Enteropeptidase cleaves at the C-terminal end of trypsinogen which activates the enzyme, turning trypsinogen into trypsin. Most of Enteropeptidase is consisted of disulfide bonds within the larger chain forming the catalytic subunits.

Caspase

Caspases are a family of cysteine proteases that play essential roles in apoptosis, necrosis, and inflammation. Caspases plays an important role in cells for apoptosis (programmed death) during the development and other stages of adult life. Caspases are also known as "executioner" proteins because of this role that they play in the cell.

Prothrombin

Prothrombin(Zymogen) is the precursor to the enzyme Thrombin which in turn converts fibrinogen in to fibrin. Fibrin is the protein responsible for blood clotting and tissue restoration during a tissue rupture. Fibrinogen is the substrate to thrombin and when activated by thrombin it becomes Fibrin a non-soluble glycol protein. Fibrimogen has a linearly symmetrical structure, containing a central cleavage site and a at both ends it has what is known as a globular unit which comes after a designated region alpha. The globular region has 2 “connection sites” Beta and Gamma. These 2 sites have the ability to connect to 2 other fibrin proteins, this allows the proteins to connect and make a lattice like structure making it a strong structure known as a cross linked fibrin clot.

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Angiotensin

Angiotensin is an oligopeptide that causes blood vessels to constrict and increased blood pressure. It also stimulates the release of aldosterone from the adrenal cortex. It is a hormone and a powerful dipsogen.