What is the Difference Between Caspase and Procaspase

The key difference between caspase and procaspase is that caspase is an active protease enzyme that is essential in apoptosis or programmed cell death, while procaspase is an inactive protease enzyme that is an inactive precursor of caspase.

Proteases are enzymes that catalyze the breakdown of peptide bonds in proteins. This reaction is called proteolysis. Proteases catalyze the conversion of large proteins into smaller peptides and single amino acids.  There are several types of proteases, such as acid, neutral, and alkaline proteases. These proteases can be obtained from plants, animals, and microorganisms. They are also found in viruses. Proteases have independently evolved multiple times in such a way that different classes of proteases can perform the same reaction by using completely different catalytic mechanisms. Caspase and procaspase are two types of proteases. Caspases are essential in apoptosis, while procaspases are the inactive precursors of caspases in cells.

CONTENTS

1. Overview and Key Difference
2. What is Caspase 
3. What is Procaspase
4. Similarities – Caspase and Procaspase
5. Caspase vs Procaspase in Tabular Form
6. Summary – Caspase vs Procaspase

What is Caspase?

Caspase is an active protease enzyme that plays an essential role in programmed cell death. It is known as caspase because of its specific cysteine protease activity. A cysteine in the active site of this enzyme nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. There are around 12 confirmed caspases in humans that perform a variety of cellular functions. There are different types of caspases as initiator, executioner, inflammatory, and other.

Figure 01: Caspase

The role of this enzyme in programmed cell death was first identified in 1993. Activation of caspase ensures that cellular components are degraded in a controlled manner. Caspase catalyzes cell death with minimal effects on surrounding tissues. This enzyme also has roles such as pyroptosis and necroptosis in programmed cell death. These forms of cell death are important for protecting an organism from cellular stress signals and pathogenic attacks. Furthermore, this enzyme has some other identified roles such as cell proliferation, tumour suppression, cell differentiation, and axon guidance and ageing. However, the overactivation of some caspases, such as caspase-3 can lead to excessive cell death. This condition is observed in several neurodegenerative diseases like Alzheimer’s disease.

What is Procaspase?

Procaspase is an inactive protease enzyme. Procaspase is an inactive zymogen that is only activated following an appropriate stimulus. The post-translational level control allows rapid and tight regulation of this enzyme. The activation process involves dimerization or often oligomerization of procaspases. Followed by the dimerization process, the procaspase is cleaved into a small subunit and a large subunit. The large and small subunits associate with each other to form an active heterodimer caspase.

Figure 02: Procaspase

The active enzyme often exists as a heterotetramer in the biological environment where a procaspase dimer is cleaved together to form a heterotetramer. Moreover, the dimerization step facilitates the activation of initiator procaspase and inflammatory procaspase. Dimerization is facilitated by binding to adaptor proteins via protein-protein interaction motifs that are in these procaspases. These motifs are called death folds. The cleavage of initiator procaspase takes place autoproteolytically, whereas initiator procaspase cleaves executioner procaspase.

What are the Similarities Between Caspase and Procaspase?

• Caspase and procaspase are two types of proteases.
• Both are proteins made up of amino acids.
• They have similarities in structure.
• They are found in humans and other mammals such as mice.
• Both are very important for cellular functions.

What is the Difference Between Caspase and Procaspase?

Caspase is an active protease enzyme important for programmed cell death, while procaspase is the inactive precursor of caspase. So, this is the key difference between caspase and procaspase. Moreover, caspase is a comparatively smaller molecule, while procaspase is a comparatively larger molecule.

The below infographic lists the differences between caspase and procaspase in tabular form for side by side comparison.

Summary – Caspase vs Procaspase

Proteases are the enzymes that break down the peptide bonds of proteins. Caspase and procaspase are two types of proteases. Caspase is an active protease enzyme, while procaspase is an inactive protease enzyme. Thus, this is the key difference between caspase and procaspase.

Reference:

1. Li, J, and J Yuan. “Caspases in Apoptosis and Beyond.” Nature News, Nature Publishing Group, 20 Oct. 2008.
2. “Procaspase 8.” An Overview | ScienceDirect Topics.

Image Courtesy:

1. “Caspase 3 final” By Tsgupta – Own work (CC BY-SA 4.0) via Commons Wikimedia
2. “Processing of procaspase-8” By Aina Estany – processing of procaspase-8 (CC BY-SA 4.0) via Commons Wikimedia

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