Zymogens - Online Tutor, Practice Problems & Exam Prep

Zymogens, or proenzymes, are inactive enzyme precursors that can be activated through proteolytic cleavage, a crucial post-translational modification. Examples include trypsinogen and chymotrypsinogen, which are stored in cells to prevent self-digestion. Once secreted, they become active enzymes, facilitating protein breakdown in the digestive system. This regulation of enzyme activity is vital for cellular integrity, ensuring that hydrolytic enzymes do not damage cellular proteins. Understanding zymogens highlights their role in metabolic processes and enzyme regulation, essential for maintaining homeostasis in biological systems.

Zymogens

In this video, we're going to introduce zymogens. So zymogens are also sometimes referred to as proenzymes. And so zymogens or proenzymes are just inactive enzyme precursors that have the potential and can be converted into active enzymes. But, again, zymogens or proenzymes are inactive enzyme precursors themselves, and so they are not active enzymes but can be converted into active enzymes. Now activation of a zymogen usually occurs via cleavage of peptide bonds. And so we already know from our previous lesson videos that proteolytic cleavage is a type of post-translational modification that regulates protein activity. And so notice down below in our image on the left-hand side, what we have is the raw protein immediately after translation, and some proteins are zymogens immediately after translation, which means that they are inactive enzyme precursors. And so zymogens can be activated into their active form, usually through proteolytic cleavage, which is why we have these scissors right here. And notice that activation will result in the active form of our protein, and of course, the inactive forms are going to be cleaved off.

Now, it's important to know that zymogens usually begin with the prefix pro or they end in the suffix o gen. And so over here on the right, what we have is a table with some examples of zymogens, which are again inactive enzyme precursors themselves. And we also have the site of synthesis. And so notice that a lot of digestive enzymes that are synthesized in either the stomach or the pancreas are going to have zymogens. And so notice that, pepsinogen, chymotrypsinogen, and trypsinogen all end in the suffix o gen, and so that indicates that these are the zymogens, the inactive enzyme precursors, of pepsin, chymotrypsin, and trypsin, peptidases that we know are active enzymes from our previous lesson videos. And also notice that procarboxypeptidase and proelastase begin with the prefix pro, which indicates that these are also zymogens, inactive enzyme precursors for the active form of the enzymes carboxypeptidase and elastase, which are also peptidases themselves. And so in our next lesson video, we're going to talk about exactly why it is that these zymogens are so important for life and important for regulating protein activity. So I'll see you guys in our next video.

Zymogens

So from way back in our previous lesson videos, we already know that both trypsin and chymotrypsin are peptidases that act as digestive enzymes. And so what we learned in our last lesson video is that both trypsin and chymotrypsin are digestive enzymes with classic examples of zymogens. And so notice down below in our image on the left-hand side towards the top in red, we have a structure that represents the inactive zymogen called trypsinogen. And we know that it is a zymogen because it ends in the suffix "ogen". And so we know that inactive zymogens are typically activated through proteolytic cleavage, which requires a peptidase to cleave off a small portion of the trypsinogen molecule. But in the process, it generates this green molecule right here that we know as the active trypsin peptidase.

And so notice down below on the bottom half of our image we have a similar representation where this red structure right here represents the inactive zymogen known as chymotrypsinogen, which again ends with the suffix "ogen", so we know it is a zymogen. And so we again know that inactive zymogens are typically activated through proteolytic cleavage, which involves a peptidase that will cleave off small portions of the chymotrypsinogen molecule, but in the process, it generates this green molecule right here that we know as the active chymotrypsin peptidase. And so notice that the chymotrypsinogen molecule has these disulfide bonds here in blue. Even through proteolytic cleavage, these disulfide bonds are not altered.

Now the question arises as to why these zymogens are so important for cells? Well, it turns out that it's actually super critical for cells to store these hydrolytic enzymes, such as trypsin and chymotrypsin, as inactive zymogens because otherwise, they could potentially kill the cell. And so notice that, up above in this image right here, what we have is this green circle here that represents our eukaryotic cell and within the eukaryotic cell we have this purple circle that represents a vesicle or a granule and within this granule, notice that we have the same exact trypsinogen molecule that we had on the left.

Inside of the cell, notice that the protein is going to be stored in its zymogen form where it is inactive. And that's a good thing because otherwise, if it were in the active trypsin form, then the trypsin could potentially be cleaving the proteins within the cell and that could potentially kill the cell. And so within the cell, it's stored as the inactive trypsinogen or inactive zymogen. And then the protein, the inactive zymogen can be secreted to the outside of the cell, essentially into the stomach, through the process of exocytosis. And, once the inactive zymogen is in the stomach, then notice that it can be activated into its active trypsin form where it can begin to break down the proteins that we've eaten inside of our stomachs.

And so again, this is all showing how by storing enzymes as zymogens, cells are able to regulate the enzymes' activity and make sure that the enzymes are not going to kill or destroy their own proteins. And so again, by storing these enzymes as zymogens, this is really a form of regulating the enzymes' activity. Which is again why we're talking about the zymogens right now. And so, this here concludes our lesson on zymogens and we'll be able to get some practice utilizing the concepts that we've learned in our next couple of videos. So I'll see you guys there.

How is chymotrypsinogen converted to chymotrypsin?

• A. A protein kinase-catalyzed phosphorylation converts chymotrypsinogen to chymotrypsin.
• B. An increase in [Ca²⁺] promotes the conversion.
• C. Proteolysis of chymotrypsinogen forms chymotrypsin.
• D. Two inactive chymotrypsinogen dimers pair to form an active chymotrypsin tetramer.

Why are most digestive enzymes produced as zymogens?

• A. To prevent digestion of cellular enzymes that would destroy the cell.
• B. So that the inactive enzyme can be transported in the bloodstream.
• C. Because the zymogen has a higher affinity for its substrate.
• D. Because the zymogen can't be post-translationally modified.

Which of the following is a zymogen that can be converted to a peptidase that hydrolyzes peptide bonds adjacent to lysine and arginine?

• A. Chymotrypsin.
• B. Pepsin.
• C. Pepsinogen.
• D. Trypsin.
• E. Trypsinogen.
• F. Proelastase.

Here’s what students ask on this topic:

What are zymogens and how are they activated?

Zymogens, also known as proenzymes, are inactive enzyme precursors that can be converted into active enzymes. Activation typically occurs through proteolytic cleavage, a process where specific peptide bonds within the zymogen are cleaved. This cleavage is a type of post-translational modification that regulates protein activity. For example, trypsinogen is a zymogen that becomes the active enzyme trypsin after cleavage. This activation mechanism ensures that enzymes are only active when and where they are needed, preventing potential damage to the cell.

Why is it important for cells to store enzymes as zymogens?

Storing enzymes as zymogens is crucial for cellular integrity. Active enzymes, especially hydrolytic ones like trypsin and chymotrypsin, can degrade cellular proteins and potentially kill the cell if not properly regulated. By storing these enzymes in their inactive zymogen form, cells prevent unwanted proteolytic activity. Once secreted outside the cell, such as into the digestive system, zymogens can be activated to perform their functions. This regulation ensures that enzymes are active only in appropriate environments, maintaining cellular and systemic homeostasis.

What are some examples of zymogens and their active forms?

Common examples of zymogens include trypsinogen, chymotrypsinogen, pepsinogen, procarboxypeptidase, and proelastase. These zymogens are inactive enzyme precursors that become active enzymes upon proteolytic cleavage. For instance, trypsinogen is converted into trypsin, chymotrypsinogen into chymotrypsin, and pepsinogen into pepsin. These active enzymes play vital roles in digestion by breaking down proteins into smaller peptides and amino acids. The naming convention often includes the prefix 'pro-' or the suffix '-ogen' to indicate their inactive zymogen form.

How does the activation of zymogens contribute to enzyme regulation?

The activation of zymogens is a key mechanism in enzyme regulation. By synthesizing enzymes in an inactive form, cells can control when and where these enzymes become active. This is particularly important for enzymes that could be harmful if active within the cell, such as digestive enzymes. Proteolytic cleavage, which activates zymogens, ensures that enzymes are only activated in specific conditions, such as in the digestive tract. This spatial and temporal regulation prevents cellular damage and allows for precise control over metabolic processes.

What role do zymogens play in the digestive system?

Zymogens play a crucial role in the digestive system by ensuring that digestive enzymes are activated only when needed. For example, trypsinogen and chymotrypsinogen are zymogens secreted by the pancreas into the small intestine. Once in the intestine, they are activated to trypsin and chymotrypsin, respectively, which then break down dietary proteins into peptides and amino acids. This activation mechanism prevents the enzymes from digesting proteins within the pancreas or other tissues, thereby protecting the body's own cells from damage.