enzymology 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 ...

, a ceramide phosphoethanolamine synthase ( EC 2.7.8.-) is an

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 ...

that

catalyzes Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

the

chemical reaction A chemical reaction is a process that leads to the chemistry, chemical transformation of one set of chemical substances to another. When chemical reactions occur, the atoms are rearranged and the reaction is accompanied by an Gibbs free energy, ...

ceramide Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid joined by an amide bond. Ceramides are found in high concentrations within the cell membrane of Eukaryote, eukaryotic cells, since they are co ...

+ a phosphoethanolamine head group donor

\rightleftharpoons

a ceramide-phosphoethanolamine + side product Ceramide phosphoethanolamine (CPE) is a

sphingolipid Sphingolipids are a class of lipids containing a backbone of sphingoid bases, which are a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sp ...

consisted of a

and a phosphoethanolamine head group. Thus, this class of enzymes uses ceramide and a donor molecule for phosphoethanolamine as

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (aquatic environment), the earthy material that exi ...

s to produce a ceramide phosphoethanolamine and a side product. The head group donor for phosphoethanolamine can be either

phosphatidylethanolamine Phosphatidylethanolamine (PE) is a class of phospholipids found in biological membranes. They are synthesized by the addition of cytidine diphosphate-ethanolamine to diglycerides, releasing cytidine monophosphate. S-Adenosyl methionine, ''S''-Ade ...

or CDP-ethanolamine, thus the side product is either a 1,2-diacylglycerol or a CMP, respectively. This enzyme belongs to the family of

transferase In biochemistry, a transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups (e.g. a methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor). They are involved ...

s, specifically those transferring non-standard substituted

phosphate Phosphates are the naturally occurring form of the element phosphorus. 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 orthop ...

groups.

Mammalian Ceramide Phosphoethanolamine Synthases

In mammalian cells, two CPE synthase activities have been described, one resides in the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

, and the other one is associated with the

plasma 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 ...

.Ternes, P., Brouwers, J. F., van den Dikkenberg, J., and Holthuis, J. C. (2009) Sphingomyelin synthase SMS2 displays dual activity as ceramide phosphoethanolamine synthase. ''J. Lipid Res''. 50, 2270–2277Vacaru, A. M., Tafesse, F. G., Ternes, P., Kondylis, V., Hermansson, M., Browers, J. F. H. M., Somerharju, P., Rabouille, C., and Holthuis, J. C. (2009) Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis in the ER. J. Cell Biol. 185, 1013–1027 The endoplasmic reticulum-resident CPE synthase, SMSr, is identified as a monofunctional CPE synthase produces trace amounts of CPE. On the other hand, mammalian CPE synthase that is on the

, SMS2, is a bifunctional enzyme that produces both CPE and

sphingomyelin Sphingomyelin (SPH, ) 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 phosphoethanolamine hea ...

, thus also functioning as a

sphingomyelin synthase In enzymology, a sphingomyelin synthase () is an enzyme that catalysis, catalyzes the chemical reaction :a ceramide + a phosphatidylcholine \rightleftharpoons a sphingomyelin + a 1,2-diacyl-sn-glycerol or the reaction using phosphatidylethanola ...

. Both mammalian CPE synthases, SMS2 and SMSr, use

(PE) as head group donor and catalyzes the reaction :a

+ a

\rightleftharpoons

a ceramide-phosphoethanolamine + 1,2-diacylglycerol

Invertebrate Ceramide Phosphoethanolamine Synthases

SMSr protein is found in all organisms throughout the animal kingdom as a CPE synthase, yet it produces trace amounts of CPE.

Drosophila ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...

and a group of

invertebrates Invertebrates are animals that neither develop nor retain a vertebral column (commonly known as a ''spine'' or ''backbone''), which evolved from the notochord. It is a paraphyletic grouping including all animals excluding the chordate subphylum ...

lack SMS2 homologues.Vacaru AM, van den Dikkenberg J, Ternes P, Holthuis JC. Ceramide phosphoethanolamine biosynthesis in Drosophila is mediated by a unique ethanolamine phosphotransferase in the Golgi lumen. J Biol Chem. 2013 Apr 19;288(16):11520-30. . Epub 2013 Feb 28. ; This group of invertebrates synthesizes CPE using a particular enzyme called CPES. CPES uses CDP-ethanolamine rather than phosphatidylethanolamine as head group donor, thus catalyzes the reaction :a

+ a CDP-ethanolamine

\rightleftharpoons

a ceramide-phosphoethanolamine + CMP CPES uses a different reaction mechanism than the one

uses, but very similar to that of enzymes involved in

synthesis Synthesis or synthesize may refer to: Science Chemistry and biochemistry *Chemical synthesis, the execution of chemical reactions to form a more complex molecule from chemical precursors **Organic synthesis, the chemical synthesis of organi ...

of phosphatidyl ethanolamine ( EC 2.7.8.1) via the Kennedy pathway.KENNEDY EP, WEISS SB. The function of cytidine coenzymes in the biosynthesis of phospholipides. ''J Biol Chem''. 1956 Sep;222(1):193-214. .

References

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