Carboxypeptidase
Encyclopedia
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....
enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that hydrolyzes
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
(cleaves) the peptide bond
Peptide bond
This article is about the peptide link found within biological molecules, such as proteins. A similar article for synthetic molecules is being created...
of an amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
residue
Residue (chemistry)
In chemistry, residue is the material remaining after a distillation or an evaporation, or to a portion of a larger molecule, such as a methyl group. It may also refer to the undesired byproducts of a reaction....
at the carboxy-terminal (C-terminal) end. (Contrast with an aminopeptidase
Aminopeptidase
Aminopeptidase is a zinc-dependent enzyme produced and secreted by glands of the small intestine. It helps the enzymatic digestion of proteins. Additional digestive enzymes produced by these glands include dipeptidases, maltase, sucrase, lactase, and enterokinase.Aminopeptidases catalyze the...
, which cleaves peptide bonds at the other end of the residue.) Humans, animals, and plants contain several types of carboxypeptidases that have diverse functions ranging from catabolism to protein maturation.
Functions
The first carboxypeptidases studied were those involved in the digestionDigestion
Digestion is the mechanical and chemical breakdown of food into smaller components that are more easily absorbed into a blood stream, for instance. Digestion is a form of catabolism: a breakdown of large food molecules to smaller ones....
of food (pancreatic carboxypeptidases A1, A2, and B). However, most of the known carboxypeptidases are not involved in catabolism
Catabolism
Catabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides, and amino...
; they help to mature proteins (e.g., Post-translational modification) or regulate biological processes. For example, the biosynthesis of neuroendocrine peptides such as insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
requires a carboxypeptidase. Carboxypeptidases also function in blood clotting, growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
production, wound healing
Wound healing
Wound healing, or cicatrisation, is an intricate process in which the skin repairs itself after injury. In normal skin, the epidermis and dermis exists in a steady-state equilibrium, forming a protective barrier against the external environment...
, reproduction, and many other processes.
By active site mechanism
Carboxypeptidases are usually classified into one of several families based on their active site mechanism.- Enzymes that use a metal in the active site are called "metallo-carboxypeptidases" (EC number 3.4.17).
- Other carboxypeptidases that use active site serineSerineSerine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
residues are called "serine carboxypeptidases" (EC number 3.4.16). - Those that use an active site cysteineCysteineCysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
are called "cysteine carboxypeptidase" (or "thiolThiolIn organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...
carboxypeptidases")(EC number 3.4.18).
These names do not refer to the selectivity of the amino acid that is cleaved.
By substrate preference
Another classification system for carboxypeptidases refers to their substrate preference.- In this classification system, carboxypeptidases that have a stronger preference for those amino acids containing aromatic or branchedBranched-chain amino acidsA branched-chain amino acid is an amino acid having aliphatic side-chains with a branch...
hydrocarbon chains are called carboxypeptidase ACarboxypeptidase ACarboxypeptidase A usually refers to the pancreatic exopeptidase which hydrolyzes peptide bonds of C-terminal residues with aromatic or aliphatic side chains...
(A for aromatic/aliphatic). - Carboxypeptidases that cleave positively charged amino acids (arginineArginineArginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
, lysineLysineLysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
) are called carboxypeptidase BCarboxypeptidase BCarboxypeptidase B is a carboxypeptidase that preferentially acts upon basic amino acids, such as arginine and lysine.-External links:* The MEROPS online database for peptidases and their inhibitors:...
(B for basicBase (chemistry)For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...
).
A metallo-carboxypeptidase that cleaves a C-terminal glutamate from the peptide N-acetyl-L-aspartyl-L-glutamate is called "glutamate carboxypeptidase".
A serine carboxypeptidase that cleaves the C-terminal residue from peptides containing the sequence -Pro-Xaa (Pro is proline, Xaa is any amino acid on the C-terminus of a peptide) is called "prolyl carboxypeptidase".
Activation
Some, but not all, carboxypeptidases are initially produced in an inactive form; this precursor form is referred to as a procarboxypeptidase. In the case of pancreatic carboxypeptidase A, the inactive zymogenZymogen
A zymogen is an inactive enzyme precursor. A zymogen requires a biochemical change for it to become an active enzyme. The biochemical change usually occurs in a lysosome where a specific part of the precursor enzyme is cleaved in order to activate it...
form - pro-carboxypeptidase A - is converted to its active form - carboxypeptidase A - by the enzyme enteropeptidase
Enteropeptidase
Enteropeptidase is an enzyme produced by cells of the duodenum and involved in human digestion. It is secreted from intestinal glands following the entry of ingested food passing from the stomach...
. This mechanism ensures that the cells wherein pro-carboxypeptidase A is produced are not themselves digested.
See also
- Carboxypeptidase ECarboxypeptidase ECarboxypeptidase E, also known as carboxypeptidase H and enkephalin convertase, is an enzyme that in humans is encoded by the CPE gene....
- Carboxypeptidase ACarboxypeptidase ACarboxypeptidase A usually refers to the pancreatic exopeptidase which hydrolyzes peptide bonds of C-terminal residues with aromatic or aliphatic side chains...
- Enzyme category EC numberEC numberThe Enzyme Commission number is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze....
3.4 - Thrombin-activatable fibrinolysis inhibitor aka plasma carboxypeptidase B2
- bacterial transpeptidaseTranspeptidaseA transpeptidase is a bacterial enzyme that cross-links the peptidoglycan chains to form rigid cell walls. This enzyme is also known by several other names including DD-peptidase, DD-transpeptidase, D-alanyl-D-alanine carboxypeptidase and serine-type D-Ala-D-Ala carboxypeptidase...
, an alanine carboxypeptidase - bradykinin is broken down among other enzymes by carboxypeptidase N
- D-Ala carboxypeptidase is a penicillin-binding protein
- PhenylalaninePhenylalaninePhenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
might inhibit carboxypeptidase A