biochemistry Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, a ...

, an ether lipid refers to any

lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...

in which the lipid "tail" group is attached to the

glycerol Glycerol () is a simple triol compound. It is a colorless, odorless, sweet-tasting, viscous liquid. The glycerol backbone is found in lipids known as glycerides. It is also widely used as a sweetener in the food industry and as a humectant in pha ...

backbone via an ether bond at any position. In contrast, conventional

glycerophospholipid Glycerophospholipids or phosphoglycerides are glycerol-based phospholipids. They are the main component of biological membranes in eukaryotic cells. They are a type of lipid, of which its composition affects membrane structure and properties. T ...

s and

triglycerides A triglyceride (from ''wikt:tri-#Prefix, tri-'' and ''glyceride''; also TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. Triglycerides are the main constituents of body fat in humans and oth ...

are tri

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

s. Structural types include: * Ether phospholipids: phospholipids are known to have ether-linked "tails" instead of the usual ester linkage. ** Ether on sn-1, ester on sn-2: "ether lipids" in the context of bacteria and eukaryotes refer to this class of lipids. Compared to the usual 1,2-diacyl-sn-glycerol (DAG), the sn-1 linkage is replaced with an ester bond.

Based on whether the sn-1 lipid is unsaturated next to the ether linkage, they can be further divided into ''alkenyl-acylphospholipids'' ("plasmenylphospholipid", 1-0-alk-1’-enyl-2-acyl-sn-glycerol) and ''alkyl-acylphospholipids'' ("plasmanylphospholipid"). This class of lipids have important roles in human cell signaling and structure.

** Ether on sn-2 and sn-3: this class with flipped

chirality Chirality () is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is distinguishable fro ...

on the phosphate connection is called an "archaeal ether lipid". With few (if any) exceptions, it is only found among

archaea Archaea ( ) is a Domain (biology), domain of organisms. Traditionally, Archaea only included its Prokaryote, prokaryotic members, but this has since been found to be paraphyletic, as eukaryotes are known to have evolved from archaea. Even thou ...

. The part excluding the phoshphate group is known as archaeol. * Ether analogues of triglycerides: 1-alkyldiacyl-sn-glycerols (alkyldiacylglycerols) are found in significant proportions in marine animals. * Other ether lipids: a number of other lipids not belonging to any of the classes above contain the ether linkage. For example, seminolipid, a vital part of the testes and sperm cells, has a ether linkage. The term "

plasmalogen Plasmalogens are a class of glycerophospholipid with a plasmenyl group linked to a lipid at the sn-1 position of the glycerol backbone. Plasmalogens are found in multiple domains of life, including Mammal, mammals, Invertebrate, invertebrates, p ...

" can refer to any ether lipid with a vinyl ether linkage, i.e. ones with a carbon-carbon

double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betw ...

next to the ether linkage. Without specification it generally refers to alkenyl-acylphospholipids, but "neutral plasmalogens" (alkenyldiacylglycerols) and "diplasmalogens" (dialkenylphospholipids) also exist.

In eukaryotes

Biosynthesis

The formation of the ether bond in mammals requires two enzymes, dihydroxyacetonephosphate acyltransferase (DHAPAT) and alkyldihydroxyacetonephosphate synthase (ADAPS), that reside in the

peroxisome A peroxisome () is a membrane-bound organelle, a type of microbody, found in the cytoplasm of virtually all eukaryotic cells. Peroxisomes are oxidative organelles. Frequently, molecular oxygen serves as a co-substrate, from which hydrogen perox ...

. Accordingly, peroxisomal defects often lead to impairment of ether-lipid production. The conversion of an ordinary saturated ether lipid into a plaminogen is achieved by plasmanylethanolamine desaturase ( PEDS1), which catalyzes an aerobic oxidation in the endoplamic reticulum. Monoalkylglycerol ethers (MAGEs) are also generated from 2-acetyl MAGEs (precursors of platelet-activating factor) by KIAA1363.

Functions

Structural

Plasmalogens as well as some 1-O-alkyl lipids are ubiquitous and sometimes major parts of the

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

s in

mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

s. The glycosylphosphatidylinositol anchor of mammalian proteins generally consist of an 1-O-alkyl lipid. 1-alkyldiacyl-''sn''-glycerols, i.e. the ether analog of

, also occur in animals. They are present in very small amounts in mammals. They are found in very high amounts in the livers of marine animals, both vertebrates like sharks (especially spiny dogfish and ratfish) and invertebrates like squids. They are also found in all corals.

Second messenger

Differences between the

catabolism Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipid ...

of ether glycerophospholipids by specific

phospholipase A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C, and D, which are distinguished by the type of reaction which they catalyze: *Phospholipase ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s might be involved in the generation of lipid

second messenger system 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 of cell signaling, encompassing both first me ...

s such as

prostaglandin Prostaglandins (PG) are a group of physiology, physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every Tissue (biology), tissue in humans and ot ...

s and

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 a precursor in the formation of leukotrienes, prostaglandins, and thromboxanes. Together with omega−3 fatty acids an ...

that are important in signal transduction. Ether lipids can also act directly in cell signaling, as the platelet-activating factor is an ether lipid signaling molecule that is involved in

leukocyte White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

function in the mammalian

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

Antioxidant

Another possible function of the plasmalogen ether lipids is as

antioxidant Antioxidants are Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants ...

s, as protective effects against

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

have been demonstrated in

cell culture Cell culture or tissue culture is the process by which cell (biology), cells are grown under controlled conditions, generally outside of their natural environment. After cells of interest have been Cell isolation, isolated from living tissue, ...

and these lipids might therefore play a role in serum lipoprotein metabolism. This antioxidant activity comes from the enol ether double bond being targeted by a variety of

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

Synthetic ether lipid analogs

Synthetic ether lipid analogs have cytostatic and cytotoxic properties, probably by disrupting membrane structure and acting as inhibitors of enzymes within signal transmission pathways, such as

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 ...

and phospholipase C. A toxic ether lipid analogue miltefosine has recently been introduced as an oral treatment for the tropical disease

leishmaniasis Leishmaniasis is a wide array of clinical manifestations caused by protozoal parasites of the Trypanosomatida genus ''Leishmania''. It is generally spread through the bite of Phlebotominae, phlebotomine Sandfly, sandflies, ''Phlebotomus'' an ...

, which is caused by

leishmania ''Leishmania'' () is a genus of parasitic protozoans, single-celled eukaryotic organisms of the trypanosomatid group that are responsible for the disease leishmaniasis. The parasites are transmitted by sandflies of the genus '' Phlebotomus'' ...

, a protozoal parasite with a particularly high ether lipid content in its membranes.

In archaea

The cell membrane of

consist mostly of ether phospholipids. These lipids have a flipped chirality compared to bacterial and eukaryotic membranes, a conundrum known as the " lipid divide". The "tail" groups are also not simply n-alkyl groups, but highly methylated chains made up of saturated isoprenoid units (e.g. phytanyl). Among different groups of archaea, diverse modifications on the basic archaeol backbone have emerged. * The two (usually C₂₀) tails can be linked together, forming a macrocyclic lipid. * Bipolar macrocyclic tetraether lipids (

caldarchaeol Caldarchaeol is a membrane-spanning lipid of the Terpenoid, isoprenoid glycerol dialkyl glycerol tetraether (Glycerol dialkyl glycerol tetraether, iGDGT) class, produced and used by archaea. Membranes made up of caldarchaeol are more stable since ...

), with two glycerol units connected by two C₄₀ "tail" chains, form

covalent A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atom ...

ly linked 'bilayers'. ** Some such covelant bilayers feature crosslinks between the two chains, giving an H-shaped molecule. ** Crenarchaeol is a tetraether backbone with cyclopentane and cyclohexane rings on the cross-linked "tail"s. See also glycerol dialkyl glycerol tetraether for more of this class * Some lipids replace the glycerol backbone with four-carbon polyols (tetriols). An example is a tetriol-diphytanyl diether.

In bacteria

Ether phospholipids are major parts of the cell membrane in anaerobic bacteria. These lipids can be variously 1-O-alkyl, 2-O-alkyl, or 1,2-O-dialkyl. Plasminogens also exist, but they are made by anaerobic reduction from an ester as opposed to the aerobic eukaryotic process. Some groups of bacteria have, like archaea, evolved tetraether lipids (so-called brGDGT). These differ from archaeal ones by their chirality and the non-isoprenoid structure.

References

External links

* {{Phospholipids Lipids