Protease enzymes - Nature Cures®

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Proteases are enzymes that break down proteins in the body to form amino acids allowing them to enter the bloodstream. This then makes them available to build all the proteins the body needs. Protease is also called peptidase, proteinase, or proteolytic enzyme.

The three stages of protein digestion

The stomach produces pepsin, a protease that begins protein digestion.
The pancreas produces proteases like trypsin, which are released into the small intestine to break down proteins.
The small intestine also contains and produces proteases, such as peptidases, to continue breaking down proteins into amino acids.

Proteases are useful in the body by helping to fight bacterial infections and parasites. There are also used in the treatment of arthritis, cancer and immune disorders.

Deficiency of protease

A deficiency in protease can cause many disorders such as constipation, digestive disorders, high blood pressure, hypoglycaemia and pancreas disorders.

Natural sources of protease enzymes in alphabetical order

Artichoke flowers (cardosin and cinarase)
Asparagus (asparagine peptide lyases)
Banana (actinidain)
Brine pickles (non-pasteurised has proteolytic activity from a complex microbial community)
Cheese (chymosin, pepsin, rennet)
Figs (actinidain and ficin)
Ginger (zingibain)
Honey (trypsin, chymotrypsin and peptidase)
Kefir (has proteolytic activity from a complex microbial community)
Kimchi (has proteolytic activity from a complex microbial community)
Kiwi fruit (actinidain
Legumes (legumain)
Mango (cysteine and serine proteases such as actinidain)
Milk (plasmin)
Miso (has proteolytic activity from a complex microbial community)
Papaya (actinidain and papain)
Pineapple (actinidain and bromelain)
Thistle (cardosin and cinarase)
Sauerkraut (has proteolytic activity from a complex microbial community)
Yoghurt (has proteolytic activity from a complex microbial community)

Classification of protease enzymes

The classification of proteases is based on the structure of their catalytic site and the key amino acid residue used as a nucleophile in the catalytic mechanism. Catalytic mechanisms are the step-by-step processes a catalyst uses to speed up a chemical reaction. They are categorised into seven classes based on their catalytic mechanism.

The seven mechanistic classes of proteases

Asparagine peptide lyases use an asparagine residue
Aspartyl proteases use an aspartate residue
Cysteine proteases use a cysteine residue
Glutamic proteases use a glutamate residue.
Metalloproteases use a metal ion, typically zinc
Serine proteases use a serine residue
Threonine proteases use a threonine residue

Asparagine peptide lyases

Asparagine peptide lyases are proteolytic enzymes that perform intramolecular self-cleavage of a peptide bond using an asparagine residue as a nucleophile, rather than the typical water molecule used by other proteases.

Aspartyl proteases

Cathepsin D is a lysosomal enzyme that performs protein degradation, activates precursors to biologically active proteins, and is involved in cellular processes like apoptosis, cell proliferation, and autophagy and is also implicated in diseases, including neurodegenerative disorders like Alzheimer’s and Parkinson’s diseases, as well as various cancers.
Cathepsin E is involved with protein degradation and acts as an anticancer protease by inducing apoptosis in tumour cells and preventing them from growing and spreading.
Pepsin is a digestive enzyme in the stomach that starts breaking down proteins into smaller peptides and amino acids.
Renin is an enzyme produced by the kidneys that plays a crucial role in regulating blood pressure and fluid balance.

Cysteine proteases

Cysteine proteases, also known as thiol proteases, are enzymes that degrade proteins and have many other functions as listed below.

Bromelain is found in pineapple juice and in the pineapple stem. It causes the body to make substances that fight pain and swelling. Bromelain also contains chemicals that interfere with tumour cell replication and can induce cancer cell death and slow blood clotting.
Calpains are calcium dependant and believed to play a role in the cell cycle and cell mobility. Cell type-specific functions have also been implicated, such as in neurons.
Caspase breaks down proteins and regulates programmed cell death (apoptosis) and inflammation.
Cathepsin B functions in the breakdown of proteins within cells, but also has roles in the immune response, hormone activation and bone turnover. It is also involved in pathological processes, such as the progression of diseases like cancer, by affecting cell death and inflammation.
Cathepsin C functions by activating other proteases, particularly serine proteases in immune and inflammatory cells. This activation is crucial for immune defence, inflammation and wound healing.
Cathepsin F is involved in protein degradation, cellular senescence, and may play a role in diseases such as cancer, autoimmune disorders, and aging-related skin conditions.
Cathepsin H has roles inprocessing peptide neurotransmitters, regulating cell migration and cancer metastasis, and playing a role in immune responses. It also has roles in both aminopeptidase and endopeptidase (protein-cutting) activities. It is expressed in many organs, including the brain, liver, lungs and pancreas.
Cathepsin K degrades type I collagen and is essential for bone resorption by osteoclasts. It also plays a fundamental role in bone remodelling.
Cathepsin L is one of the key proteases upregulated in granulosa cells of ovulatory follicles mediating follicular rupture during ovulation. Studies have indicated that cathepsin L could be a promising therapeutic target for the prevention and treatment of COVID-19.
Cathepsin O is involved in protein degradation and turnover, and it can also degrade extracellular matrix proteins like fibrinogen at acidic ph. It is also the innate immune response and in the degradation of bone matrix and collagen, similar to related enzymes.
Cathepsin S allows foreign protein fragments (antigens) to be properly loaded onto MHC II molecules for presentation to T cells, which is a key step in initiating an adaptive immune response. It also plays a role in processes involving tissue remodelling.
Cathepsin V is involved in protein degradation, including elastin and other extracellular matrix components. It plays roles in immune functions, such as processing major histocompatibility complex class II molecules, and in generating neuropeptides like enkephalin and neuropeptide Y.
Cathepsin W plays a role in immune regulation and viral infections by participating in protein processing and degradation. It is found in immune cells like CD8+ T cells and natural killer cells.
Cathepsin X regulates processes like cell migration, adhesion, and immune responses. It is involved in activating immune cells, such as T-lymphocytes, through its interaction with integrin receptors, and it can play a role in diseases like cancer and neurodegenerative disorders.
Legumain found in legumes and other seeds can cleave proteins to degrade or activate them. It can also act like a ligase and join molecules together. Legumain can also inhibit osteoblast differentiation by degrading fibronectin which involves the bones.
Papain breaks down proteins into smaller peptides and amino acids. It is derived from the latex found in raw, unripe papaya fruit.

Glutamic proteases

Glutamic proteases are enzymes that break down proteins, primarily found in fungi, and are involved in various biological processes, including pathogenicity and disease.

Aspergilloglutamic peptidase from the fungi Aspergillus niger
Scytalidoglutamic peptidase from the fungi Scytalidium lignicola

Metalloproteases

Break down proteins, such as collagen found in the spaces between cells in tissues. Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases.

Collagenases are responsible for breaking down interstitial collagens.
Gelatinases degrade gelatine, denatured collagen, and other non-fibrillar collagens like types IV and V.
Stromelysins degrade proteoglycans, fibronecti, and laminin.
Matrilysins degrade a wide variety of extracellular matrix molecules which are structural and signalling molecules secreted by cells that provide support for tissues and regulate cellular functions.
Membrane-type (MT)-MMPs play a crucial role in cell-surface-mediated ECM remodelling and can activate other matrix metalloproteinases (MMPs) which is crucial for processes like tissue repair, wound healing and development.

Serine proteases

Cathepsin A acts as a protective protein, interacting with other enzymes to prevent them from breaking down prematurely.
Cathepsin G has a dual role in the immune system, acting both to clear pathogens and regulate inflammation. However, it can also have detrimental effects in autoimmune diseases, chronic inflammation, and cancer.
Chymotrypsin is an enzyme in the small intestines that breaks down large proteins and polypeptides into smaller peptides
Elastase is a pancreatic enzyme that breaks down proteins like elastin.
Granzymes are enzymes that trigger apoptosis (programmed cell death) in target cells.
Kallikreins are involved in various physiological processes including blood pressure regulation and inflammation.
Penicillin acylase is an enzyme found in bacteria, fungi and yeast.
Plasmin is an enzyme that breaks down blood clots.
Thrombin is an enzyme crucial for blood clotting by converting fibrinogen to fibrin.
Tissue plasminogen activator (tPA) is an enzyme involved in dissolving blood clots.
Trypsin is a digestive enzyme produced by the pancreas that breaks down proteins in the small intestine into smaller peptides and amino acids, which the body can then absorb.

Threonine proteases

Glycosylasparaginase is a lysosomal amidase enzyme that plays a key role in the final stages of glycoprotein degradation. A deficiency in this enzyme causes the lysosomal storage disorder known as aspartylglucosaminuria.
Proteasomes are protein recycling machines that break down unwanted proteins into smaller peptides through a process called proteolysis.
Heat Shock Locus V (peptidase component) and Heat Shock Locus U (ATPase component) complex. (HslVU) is responsible for maintaining cellular protein homeostasis by degrading damaged, abnormal, or short-lived regulatory proteins in an energy-dependent manner. It is an ATP-dependent proteolytic complex present in certain bacteria and in the mitochondrion of some primordial eukaryotes, including deadly parasites.

NOTE: Cathepsin V is also known as Cathepsin L2. Cathepsin X is also known as Cathepsin Z (or sometimes Cathepsin P).

All these enzymes play vital roles in cellular processes such as protein degradation, immune response, and bone remodelling. Any dysfunction of these enzymes can be associated with various diseases, including cancer and neurodegenerative disorders.

External references

For more information about the 1000 listed proteases also termed as peptidases, proteinases and proteolytic enzymes see The MEROPS Database

Reference for Cathepsin L and Covid-19

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