Cathepsin
Encyclopedia
Cathepsins are protease
s: protein
s that break apart other proteins, found in many types of cell
s including those in all animals. There are approximately a dozen members of this family, which are distinguished by their structure, catalytic mechanism, and which proteins they cleave. Most of the members become activated at the low pH found in lysosomes. Thus, the activity of this family lies almost entirely within those organelles. There are, however, exceptions such as cathepsin K, which works extracellularly after secretion by osteoclasts in bone resorption.
Cathepsins have a vital role in mammalian cellular turnover, e.g. bone resorption
. They degrade polypeptide
s and are distinguished by their substrate
specificites.
. The cathepsin A activity in lysates of metastatic lesions of malignant melanoma is significantly higher than in primary focus lysates. Cathepsin A increased in muscles moderately affected by muscular dystrophy and denervating diseases.
. Cathepsin B is also involved in apoptosis as well as degradation of myofibrillar proteins in myocardial infarction
.
and laminin
. High levels of this enzyme in tumor cells seems to be associated with greater invasiveness.
database (e.g. via PubMed
) is from the Journal of Biological Chemistry
in 1949.
However, references within this article indicate that cathepsins were first identified and named around the turn of the 20th century. Much of this earlier work was done in the laboratory of Max Bergmann
, who spent the first several decades of the century defining these proteases.
Protease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
s: protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s that break apart other proteins, found in many types of cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s including those in all animals. There are approximately a dozen members of this family, which are distinguished by their structure, catalytic mechanism, and which proteins they cleave. Most of the members become activated at the low pH found in lysosomes. Thus, the activity of this family lies almost entirely within those organelles. There are, however, exceptions such as cathepsin K, which works extracellularly after secretion by osteoclasts in bone resorption.
Cathepsins have a vital role in mammalian cellular turnover, e.g. bone resorption
Bone resorption
Bone resorption is the process by which osteoclasts break down bone and release the minerals, resulting in a transfer of calcium from bone fluid to the blood....
. They degrade polypeptide
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s and are distinguished by their substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
specificites.
Classification
- Cathepsin ACathepsin ACathepsin A is an enzyme which is classified both as a cathepsin and a carboxypeptidase. In humans, it is encoded by the CTSA gene.- Function :...
(serine proteaseSerine proteaseSerine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...
) - Cathepsin BCathepsin BCathepsin B is an enzymatic protein belonging to the peptidase families. In humans, it is coded by the CTSB gene.- Function :...
(cysteine proteaseCysteine proteaseProteases are enzymes that degrade polypeptides. Cysteine proteases have a common catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic dyad. The first step is deprotonation of a thiol in the enzyme's active site by an adjacent amino acid with a basic side chain, usually a...
) - Cathepsin CCathepsin CCathepsin C also known as dipeptidyl peptidase I is a lysosomal exo-cysteine protease belonging to the peptidase C1 family...
(cysteine protease) - Cathepsin D (aspartyl protease)
- Cathepsin E (aspartyl protease)
- Cathepsin F (cysteine proteinase)
- Cathepsin GCathepsin GCathepsin G is an enzymatic protein belonging to the peptidase or protease families. In humans, it is coded by the CTSG gene.The protein encoded by this gene, a member of the peptidase S1 protein family, is found in azurophil granules of neutrophilic polymorphonuclear leukocytes...
(serine protease) - Cathepsin H (cysteine protease)
- Cathepsin KCathepsin KCathepsin K, abbreviated CTSK, is an enzyme which in humans is encoded by the CTSK gene.- Function :The protein encoded by this gene is a lysosomal cysteine protease involved in bone remodeling and resorption...
(cysteine protease) - Cathepsin L1 (cysteine protease)
- Cathepsin L2 (or V) (cysteine protease)
- Cathepsin OCathepsin OCathepsin O is an enzyme that in humans is encoded by the CTSO gene.- Function :Cathepsin O is a cysteine protease and a member of the cathepsin family and papain superfamily. This proteolytic enzyme is involved in cellular protein degradation and turnover...
(cysteine protease) - Cathepsin SCathepsin SCathepsin S, also known as CTSS, is a protein which in humans is encoded by the CTSS gene.The protein encoded by this gene, a member of the peptidase C1 family, is a lysosomal cysteine protease that may participate in the degradation of antigenic proteins to peptides for presentation on MHC class...
(cysteine protease) - Cathepsin W (cysteine proteinase)
- Cathepsin Z (or X) (cysteine protease)
Clinical significance
Cathepsins have been implicated in:- CancerCancerCancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
- StrokeStrokeA stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
- Alzheimer's diseaseAlzheimer's diseaseAlzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, - ArthritisArthritisArthritis is a form of joint disorder that involves inflammation of one or more joints....
- EbolaEbolaEbola virus disease is the name for the human disease which may be caused by any of the four known ebolaviruses. These four viruses are: Bundibugyo virus , Ebola virus , Sudan virus , and Taï Forest virus...
, Cathepsin L and to a lesser extent cathepsin B have been found to be necessary for the virus to enter host cells. - COPDChronic obstructive pulmonary diseaseChronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...
- Chronic periodontitisChronic periodontitisChronic periodontitis is a common disease of the oral cavity consisting of chronic inflammation of the periodontal tissues that is caused by accumulation of profuse amounts of dental plaque.-Diagnosis:...
- Several ocular disorders: keratoconusKeratoconusKeratoconus , is a degenerative disorder of the eye in which structural changes within the cornea cause it to thin and change to a more conical shape than its normal gradual curve....
, retinal detachmentRetinal detachmentRetinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blindness. It is a medical emergency.The retina is a...
, age-related macular degeneration, and glaucomaGlaucomaGlaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
.
Cathepsin A
Deficiencies in this protein are linked to multiple forms of galactosialidosisGalactosialidosis
Galactosialidosis is a lysosomal storage disease.It is associated with cathepsin A.-External links:*...
. The cathepsin A activity in lysates of metastatic lesions of malignant melanoma is significantly higher than in primary focus lysates. Cathepsin A increased in muscles moderately affected by muscular dystrophy and denervating diseases.
Cathepsin B
Cathepsin B seems to actually break down the proteins which cause amyloid plaque, the root of Alzheimer's symptoms, and may even be a pivotal part of the natural defense against this disease used by people who do not get it. Overexpression of the encoded protein, which is a member of the peptidase C1 family, has been associated with esophageal adenocarcinoma and other tumors. Cathepsin B has also been implicated in the progression of various human tumors including ovarian cancerOvarian cancer
Ovarian cancer is a cancerous growth arising from the ovary. Symptoms are frequently very subtle early on and may include: bloating, pelvic pain, difficulty eating and frequent urination, and are easily confused with other illnesses....
. Cathepsin B is also involved in apoptosis as well as degradation of myofibrillar proteins in myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
.
Cathepsin D
Cathepsin D (an aspartyl protease) appears to cleave a variety of substrates such as fibronectinFibronectin
Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...
and laminin
Laminin
Laminins are major proteins in the basal lamina , a protein network foundation for most cells and organs...
. High levels of this enzyme in tumor cells seems to be associated with greater invasiveness.
History
The earliest record of "cathepsin" found in the MEDLINEMEDLINE
MEDLINE is a bibliographic database of life sciences and biomedical information. It includes bibliographic information for articles from academic journals covering medicine, nursing, pharmacy, dentistry, veterinary medicine, and health care...
database (e.g. via PubMed
PubMed
PubMed is a free database accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine at the National Institutes of Health maintains the database as part of the Entrez information retrieval system...
) is from the Journal of Biological Chemistry
Journal of Biological Chemistry
The Journal of Biological Chemistry is a weekly peer-reviewed scientific journal that was established in 1905. Since 1925 it is published by the American Society for Biochemistry and Molecular Biology. It covers research in any area of biochemistry or molecular biology. The editor-in-chief is...
in 1949.
However, references within this article indicate that cathepsins were first identified and named around the turn of the 20th century. Much of this earlier work was done in the laboratory of Max Bergmann
Max Bergmann
Max Bergmann was a Jewish-German biochemist. He was the first to use the Carboxybenzyl protecting group for the synthesis of oligopeptides.-Life and work:Bergmann was born in Fürth, Bavaria, Germany on February 12, 1886....
, who spent the first several decades of the century defining these proteases.
External links
- The MEROPSMeropsMerops may refer to:* Merops , a genus of bee-eaters.* MEROPS, an on-line database for peptidases.It may also refer to several figures from Greek mythology:* King of Ethiopia, husband of Clymene, who lay with Helios and bore Phaethon...
online database for peptidases and their inhibitors: A01.010