Phospholipase C (PLC) is a class of membrane-associated
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
s that cleave
phospholipid
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
s just before the
phosphate
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid .
The phosphate or orthophosphate ion is derived from phospho ...
group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role in
eukaryotic
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...
physiology
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...
, in particular
signal transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...
pathways. Phospholipase C's role in signal transduction is its cleavage of
phosphatidylinositol 4,5-bisphosphate
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of ...
(PIP
2) into
diacyl glycerol
A diglyceride, or diacylglycerol (DAG), is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Two possible forms exist, 1,2-diacylglycerols and 1,3-diacylglycerols. DAGs can act as sur ...
(DAG) and
inositol 1,4,5-trisphosphate
Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the ...
(IP
3), which serve as
second messengers
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form or cell signaling, encompassing both first me ...
. Activators of each PLC vary, but typically include
heterotrimeric G protein
Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a Heteromer, heterotrimeric complex. The biggest no ...
subunits, protein
tyrosine kinases
A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.
Tyrosine kinases belong to a larger cla ...
,
small G proteins, Ca
2+, and phospholipids.
There are thirteen kinds of mammalian phospholipase C that are classified into six isotypes (β, γ, δ, ε, ζ, η) according to structure. Each PLC has unique and overlapping controls over expression and subcellular distribution.
Variants
Mammalian variants
The extensive number of functions exerted by the PLC reaction requires that it be strictly regulated and able to respond to multiple extra- and intracellular inputs with appropriate kinetics. This need has guided the evolution of six isotypes of PLC in animals, each with a distinct mode of regulation. The pre-mRNA of PLC can also be subject to differential splicing such that a mammal may have up to 30 PLC enzymes.
* beta:
PLCB1
1-Phosphatidylinositol-4,5-bisphosphate phospholipase beta-1 is an enzyme that in humans is encoded by the ''PLCB1'' gene.
Function
The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol fro ...
,
PLCB2
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-2 is an enzyme that in humans is encoded by the ''PLCB2'' gene.
Function
The gene codes for the enzyme phospholipase C β2. The enzyme catalyzes the formation of inositol 1,4,5-tri ...
,
PLCB3
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-3 is an enzyme that in humans is encoded by the ''PLCB3'' gene.
The gene codes for the enzyme phospholipase C β3. The enzyme catalyzes the formation of inositol 1,4,5-trisphosphate an ...
,
PLCB4
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-4 is an enzyme that in humans is encoded by the ''PLCB4'' gene.
Function
The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol ...
* gamma:
PLCG1
Phospholipase C, gamma 1, also known as PLCG1,is a protein that in humans involved in cell growth, migration, apoptosis, and proliferation. It is encoded by the ''PLCG1'' gene and is part of the PLC superfamily.
Function
PLCγ1 is a cell grow ...
,
PLCG2
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-2 is an enzyme that in humans is encoded by the ''PLCG2'' gene.
Function
Enzymes of the phospholipase C family catalyze the hydrolysis of phospholipids to yield diacylglycerols an ...
* delta:
PLCD1
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-1 is an enzyme that in humans is encoded by the ''PLCD1'' gene.
PLCd1 is essential to maintain homeostasis of the skin.
See also
Phospholipase C
Phospholipase C (PLC) is a class of ...
,
PLCD3
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-3 is an enzyme that in humans is encoded by the ''PLCD3'' gene.
Function
This gene encodes a member of the phospholipase C family, which catalyze the hydrolysis of phosphatidylin ...
,
PLCD4
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase delta-4 is an enzyme that in humans is encoded by the ''PLCD4'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units o ...
* epsilon:
PLCE1
1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase epsilon-1 (PLCE1) is an enzyme that in humans is encoded by the ''PLCE1'' gene. This gene encodes a phospholipase enzyme (PLCE1) that catalyzes the hydrolysis of phosphatidylinositol-4,5-bis ...
* eta:
PLCH1,
PLCH2 PLCH may stand for:
* Plch, a municipality in the Czech Republic
* The Public Library of Cincinnati and Hamilton County
Cincinnati and Hamilton County Public Library (CHPL) is a public library system in the United States. In addition t ...
* zeta:
PLCZ1
* phospholipase C-like:
PLCL1,
PLCL2 PLCL may refer to:
* Park Lane College Leeds, a former British further education college, now part of Leeds City College
* ''Parker Lewis Can't Lose
''Parker Lewis Can't Lose'' is an American teen sitcom that originally aired on Fox from Sept ...
Bacterial variants
Most of the bacterial variants of phospholipase C are characterized into one of four groups of structurally related proteins. The toxic phospholipases C are capable of interacting with eukaryotic cell membranes and hydrolyzing phosphatidylcholine and sphingomyelin, ultimately leading to cell lysis.
*Zinc-metallophospholipases C: ''
Clostridium perfringens
''Clostridium perfringens'' (formerly known as ''C. welchii'', or ''Bacillus welchii'') is a Gram-positive, rod-shaped, anaerobic, spore-forming pathogenic bacterium of the genus '' Clostridium''. ''C. perfringens'' is ever-present in nature an ...
''
alpha-toxin, ''
Bacillus cereus
''Bacillus cereus'' is a Gram-positive rod-shaped bacterium commonly found in soil, food, and marine sponges. The specific name, ''cereus'', meaning "waxy" in Latin, refers to the appearance of colonies grown on blood agar. Some strains are ha ...
''
PLC (BC-PLC)
*Sphingomyelinases: ''B. cereus'', ''
Staphylococcus aureus
''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive ...
''
*Phosphatidylinositol-hydrolyzing enzymes: ''B. cereus'', ''
B. thuringiensis
''Bacillus thuringiensis'' (or Bt) is a gram-positive, soil-dwelling bacterium, the most commonly used biological pesticide worldwide. ''B. thuringiensis'' also occurs naturally in the gut of caterpillars of various types of moths and butterflie ...
'', ''
L. monocytogenes'' (PLC-A)
*Pseudomonad phospholipases C: ''
Pseudomonas aeruginosa
''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aerugi ...
'' (PLC-H and PLC-N)
Enzyme structure
![Comparison of C2 domain of mammalian PI-PLC in red and C2-like domain of Bacillus cereus in cyan](https://upload.wikimedia.org/wikipedia/commons/4/4f/Comparison_of_C2_domain_of_mammalian_PI-PLC_in_red_and_C2-like_domain_of_Bacillus_cereus_in_cyan.png)
In mammals, PLCs share a conserved core structure and differ in other domains specific for each family. The core enzyme includes a split
triosephosphate isomerase (TIM) barrel,
pleckstrin homology (PH) domain, four tandem
EF hand domains, and a
C2 domain
A C2 domain is a protein structural domain involved in targeting proteins to cell membranes. The typical version (PKC-C2) has a beta-sandwich composed of 8 beta sheet, β-strands that co-ordinates two or three calcium ions, which bind in a cavity ...
.
The TIM barrel contains the active site, all catalytic residues, and a Ca
2+ binding site. It has an autoinhibitory insert that interrupts its activity called an X-Y linker. The X-Y linker has been shown to occlude the active site, and with its removal PLC is activated.
The genes encoding
alpha-toxin (''Clostridium perfringens''), ''
Bacillus cereus
''Bacillus cereus'' is a Gram-positive rod-shaped bacterium commonly found in soil, food, and marine sponges. The specific name, ''cereus'', meaning "waxy" in Latin, refers to the appearance of colonies grown on blood agar. Some strains are ha ...
''
PLC (BC-PLC), and PLCs from ''
Clostridium bifermentans
''Paraclostridium bifermentans'', formerly known as ''Clostridium bifermentans'' and abbreviated CLOBI, is an anaerobic, motile, gram-positive bacterium.
Toxins and mosquito larvae
A certain subspecies, ''Clostridium bifermentans'' subsp. Malays ...
'' and ''
Listeria monocytogenes
''Listeria monocytogenes'' is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the host' ...
'' have been isolated and nucleotides sequenced. There is significant homology of the sequences, approximately 250 residues, from the N-terminus. Alpha-toxin has an additional 120 residues in the C-terminus. The C-terminus of the alpha-toxin has been reported as a “C2-like” domain, referencing the
C2 domain
A C2 domain is a protein structural domain involved in targeting proteins to cell membranes. The typical version (PKC-C2) has a beta-sandwich composed of 8 beta sheet, β-strands that co-ordinates two or three calcium ions, which bind in a cavity ...
found in eukaryotes that are involved in signal transduction and present in mammalian
phosphoinositide phospholipase C
Phosphoinositide phospholipase C (PLC, EC 3.1.4.11, triphosphoinositide phosphodiesterase, phosphoinositidase C, 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase, monophosphatidylinositol phosphodiesterase, phosphatidylinositol phosph ...
.
Enzyme mechanism
The primary catalyzed reaction of PLC occurs on an insoluble substrate at a lipid-water interface. The residues in the active site are conserved in all PLC isotypes. In animals, PLC selectively catalyzes the hydrolysis of the phospholipid
phosphatidylinositol 4,5-bisphosphate (PIP2) on the glycerol side of the phosphodiester bond. There is the formation of a weakly enzyme-bound intermediate, inositol 1,2-cyclic phosphodiester, and release of
diacylglycerol (DAG). The intermediate is then hydrolyzed to
inositol 1,4,5-trisphosphate (IP3). Thus the two end products are DAG and IP
3. The acid/base catalysis requires two conserved histidine residues and a Ca
2+ ion is needed for PIP
2 hydrolysis. It has been observed that the active-site Ca
2+ coordinates with four acidic residues and if any of the residues are mutated then a greater Ca
2+ concentration is needed for catalysis.
Regulation
Activation
Receptors that activate this pathway are mainly
G protein-coupled receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...
s coupled to the
Gαq subunit, including:
*
5-HT2 serotonergic receptors
*
α1 (Alpha-1) adrenergic receptors
The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta ...
[ Page 104]
*
Calcitonin receptor
The calcitonin receptor (CT) is a G protein-coupled receptor that binds the peptide hormone calcitonin and is involved in maintenance of calcium homeostasis, particularly with respect to bone formation and metabolism.
CT works by activating the G ...
s
*
H1 histamine receptors
The histamine receptors are a class of G protein–coupled receptors which bind histamine as their primary endogenous ligand.
There are four known histamine receptors:
* H1 receptor
* H2 receptor
* H3 receptor
* H4 receptor
Comparison
There ...
*
Metabotropic glutamate receptors
The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate rece ...
, Group I
*
M1,
M3, and
M5 muscarinic receptors
Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rece ...
* Thyroid-Releasing Hormone receptor in anterior pituitary gland
Other, minor, activators than G
αq are:
*
MAP kinase
A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase). MAPKs are involved in directing cellular responses ...
. Activators of this pathway include
PDGF
Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing blood v ...
and
FGF.
[
* βγ-complex of ]heterotrimeric G-protein
Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a heterotrimeric complex. The biggest non-structura ...
s, as in a minor pathway of growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
release by growth hormone-releasing hormone
Growth may refer to:
Biology
* Auxology, the study of all aspects of human physical growth
* Bacterial growth
* Cell growth
* Growth hormone, a peptide hormone that stimulates growth
* Human development (biology)
* Plant growth
* Secondary growth ...
.[GeneGlobe -> GHRH Signaling]
Retrieved on May 31, 2009
* Cannabinoid receptor
Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid recepto ...
s
Inhibition
*Small molecule U73122: aminosteroid, putative PLC inhibitor. However, the specificity of U73122 has been questioned. It has been reported that U73122 activates the phospholipase activity of purified PLCs.
*Edelfosine
Edelfosine (ET-18-O-CH3; 1-octadecyl-2-''O''-methyl-glycero-3-phosphocholine) is a synthetic alkyl-lysophospholipid (ALP). It has antineoplastic (anti-cancer) effects.
Like all ALPs, it incorporates into the cell membrane and does not target t ...
: lipid-like, anti-neoplastic agent (ET-18-OCH3)
*Autoinhibition of X-Y linker in mammalian cells: It is proposed that the X-Y linker consists of long stretches of acidic amino acids that form dense areas of negative charge. These areas could be repelled by the negatively charged membrane upon binding of the PLC to membrane lipids. The combination of repulsion and steric constraints is thought to remove the X-Y linker from near the active site and relieve auto-inhibition.
*Compounds containing the morpholinobenzoic acid scaffold belong to a class of drug-like phosphatidylcholine-specific PLC inhibitors.
*''o''-phenanthroline: heterocyclic organic compound, known to inhibit zinc-metalloenzymes
*EDTA: molecule that chelates Zn2+ ions and effectively inactivates PLC, known to inhibit zinc-metalloenzymes
Biological function
PLC cleaves the phospholipid
Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
phosphatidylinositol 4,5-bisphosphate
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of ...
(PIP2) into diacyl glycerol
A diglyceride, or diacylglycerol (DAG), is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Two possible forms exist, 1,2-diacylglycerols and 1,3-diacylglycerols. DAGs can act as sur ...
(DAG) and inositol 1,4,5-trisphosphate
Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the ...
(IP3). Thus PLC has a profound impact on the depletion of PIP2, which acts as a membrane anchor or allosteric regulator and an agonist for many lipid-gated ion channels
Lipid-gated ion channels are a class of ion channels whose conductance of ions through the membrane depends directly on lipids. Classically the lipids are membrane resident anionic signaling lipids that bind to the transmembrane domain on the inn ...
. PIP2 also acts as the substrate for synthesis of the rarer lipid phosphatidylinositol 3,4,5-trisphosphate (PIP3), which is responsible for signaling in multiple reactions. Therefore, PIP2 depletion by the PLC reaction is critical to the regulation of local PIP3 concentrations both in the plasma membrane and the nuclear membrane.
The two products of the PLC catalyzed reaction, DAG and IP3, are important second messengers that control diverse cellular processes and are substrates for synthesis of other important signaling molecules. When PIP2 is cleaved, DAG remains bound to the membrane, and IP3 is released as a soluble structure into the cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
. IP3 then diffuses through the cytosol to bind to IP3 receptors, particularly calcium channel
A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels.
Comparison tables
The following tables e ...
s in the smooth endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...
(ER). This causes the cytosolic concentration of calcium to increase, causing a cascade of intracellular changes and activity.[ In addition, calcium and DAG together work to activate ]protein kinase C
In cell biology, Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...
, which goes on to phosphorylate other molecules, leading to altered cellular activity. End-effects include taste, tumor promotion, as well as vesicle exocytosis, superoxide
In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of the ...
production from NADPH oxidase
NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) is a membrane-bound enzyme complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white ...
, and JNK
c-Jun N-terminal kinases (JNKs), were originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to the mitogen-activated protein kinase family, and are ...
activation.
Both DAG and IP3 are substrates for the synthesis of regulatory molecules. DAG is the substrate for the synthesis of phosphatidic acid Phosphatidic acids are anionic phospholipids important to cell signaling and direct activation of lipid-gated ion channels. Hydrolysis of phosphatidic acid gives rise to one molecule each of glycerol and phosphoric acid and two molecules of fatty ac ...
, a regulatory molecule. IP3 is the rate-limiting substrate for the synthesis of inositol polyphosphates, which stimulate multiple protein kinases, transcription, and mRNA processing.
Regulation of PLC activity is thus vital to the coordination and regulation of other enzymes of pathways that are central to the control of cellular physiology.
Additionally, phospholipase C plays an important role in the inflammation pathway. The binding of agonists such as thrombin
Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma- ...
, epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
, or collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...
, to platelet
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
surface receptors can trigger the activation of phospholipase C to catalyze the release of arachidonic acid
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachi ...
from two major membrane phospholipids, phosphatidylinositol
Phosphatidylinositol (or Inositol Phospholipid) consists of a family of lipids as illustrated on the right, where red is x, blue is y, and black is z, in the context of independent variation, a class of the phosphatidylglycerides. In such molecul ...
and phosphatidylcholine
Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup.
They are a major component of biological membranes and can be easily obtained from a variety of readily available sources, such as egg yolk or soyb ...
. Arachidonic acid can then go on into the cyclooxygenase pathway (producing prostoglandins (PGE1, PGE2, PGF2), prostacyclins (PGI2), or thromboxanes
Thromboxane is a member of the family of lipids known as eicosanoids. The two major thromboxanes are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6-membered ether-containing ring.
Thromboxane is named for its ...
(TXA2)), and the lipoxygenase pathway (producing leukotrienes
Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase.
Leukotrienes ...
(LTB4, LTC4, LTD4, LTE4)).
The bacterial variant ''Clostridium perfringens'' type A produces alpha-toxin. The toxin has phospholipase C activity, and causes hemolysis
Hemolysis or haemolysis (), also known by several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo o ...
, lethality, and dermonecrosis. At high concentrations, alpha-toxin induces massive degradation of phosphatidylcholine
Phosphatidylcholines (PC) are a class of phospholipids that incorporate choline as a headgroup.
They are a major component of biological membranes and can be easily obtained from a variety of readily available sources, such as egg yolk or soyb ...
and sphingomyelin
Sphingomyelin (SPH, ˌsfɪŋɡoˈmaɪəlɪn) is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide, or a ethano ...
, producing diacylglycerol and ceramide
Ceramides are a family of waxy lipid molecules. A ceramide is composed of N-acetylsphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make up ...
, respectively. These molecules then participate in signal transduction pathways. It has been reported that the toxin activates the arachidonic acid cascade in isolated rat aorta. The toxin-induced contraction was related to generation of thromboxane A2 from arachidonic acid. Thus it is likely the bacterial PLC mimics the actions of endogenous PLC in eukaryotic cell membranes.
See also
* Glycosylphosphatidylinositol diacylglycerol-lyase A trypanosomal enzyme.
* Phosphatidylinositol diacylglycerol-lyase Another related bacterial enzyme
* Phosphoinositide phospholipase C
Phosphoinositide phospholipase C (PLC, EC 3.1.4.11, triphosphoinositide phosphodiesterase, phosphoinositidase C, 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase, monophosphatidylinositol phosphodiesterase, phosphatidylinositol phosph ...
The main form found in eukaryotes, especially mammals.
* Zinc-dependent phospholipase C
In molecular biology, zinc-dependent phospholipases C is a family of bacterial phospholipases C enzymes, some of which are also known as alpha toxins.
''Bacillus cereus'' contains a monomeric phospholipase C (PLC) of 245 amino-acid residues. ...
family of bacterial enzymes that includes the alpha toxins of ''C. perfringens
''Clostridium perfringens'' (formerly known as ''C. welchii'', or ''Bacillus welchii'') is a Gram-positive, rod-shaped, anaerobic, spore-forming pathogenic bacterium of the genus ''Clostridium''. ''C. perfringens'' is ever-present in nature and ...
'' (also known as lecithinase Lecithinase is a type of phospholipase that acts upon lecithin.
It can be produced by ''Clostridium perfringens'', ''Staphylococcus aureus'', ''Pseudomonas aeruginosa'' or ''Listeria monocytogenes''. ''C. perfringens'' alpha toxin (lecithinase) c ...
), ''P. aeruginosa P. is an abbreviation or acronym that may refer to:
* Page (paper), where the abbreviation comes from Latin ''pagina''
* Paris Herbarium, at the ''Muséum national d'histoire naturelle''
* ''Pani'' (Polish), translating as Mrs.
* The ''Pacific Repo ...
'', and '' S. aureus''.
References
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EC 3.1.4