Ceramide synthase 4 (CerS4) is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

that in humans is encoded by the CERS4 gene and is one of the least studied of the

ceramide synthase In enzymology, sphingosine N-acyltransferases (ceramide synthases (CerS), ) are enzymes that catalyze the chemical reaction of synthesis of ceramide: :acyl-CoA + sphingosine \rightleftharpoons CoA + N-acylsphingosine Thus, the two substrates of ...

Function and distribution

CerS4 synthesizes

ceramides 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 u ...

containing C18-22

fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...

s in a

fumonisin B1 Fumonisin B1 is the most prevalent member of a family of toxins, known as fumonisins, produced by several species of '' Fusarium'' molds, such as '' Fusarium verticillioides'', which occur mainly in maize (corn), wheat and other cereals. Fumonis ...

-independent manner. It is expressed at highest levels in

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

leukocyte White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mul ...

heart The heart is a muscular organ found in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon diox ...

and

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

, although at much lower levels than other ceramide synthases.

Tissue and cellular distribution

CerS4 (TRH1) mRNA was found in all tissues and is strongly expressed in skin and muscle

Clinical significance

In a 2009 study of

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...

, total ceramide synthase levels were increased in malignant tissue, and CerS4 was one of three ceramide synthases to show an increase in

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...

levels. A significant correlation was found between CerS4 and CerS2/ CerS6 expression. Unlike

CerS1 Ceramide synthase 1 also known as LAG1 longevity assurance homolog 1 is an enzyme that in humans is encoded by the ''CERS1'' gene. Function This gene encodes a member of the bone morphogenetic protein (BMP) family and the TGF-beta superfamil ...

and

CerS5 Ceramide synthase 5 (CerS5) is the enzyme encoded in humans by the CERS5 gene. Function CerS5 robustly synthesizes C16-ceramide, which is often considered to be an important pro-apoptotic ceramide. De novo ceramide synthesis is an essential trig ...

, CerS4 does not sensitize cells to chemotherapeutic drugs. CerS4 may also be involved in the control of

body weight Human body weight is a person's Mass versus weight, mass or weight. Strictly speaking, body weight is the measurement of weight without items located on the person. Practically though, body weight may be measured with clothes on, but without shoe ...

and

food intake Eating (also known as consuming) is the ingestion of food, typically to provide a heterotrophic organism with energy and to allow for growth. Animals and other heterotrophs must eat in order to survive — carnivores eat other animals, herb ...

. Upon administration of

leptin Leptin (from Greek λεπτός ''leptos'', "thin" or "light" or "small") is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate energy balance by inhibiting hunger, which in turn dimi ...

, a decrease in ceramide levels was observed in

rat Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include '' Neotoma'' ( pack rats), '' Bandicota'' (bandico ...

white adipose tissue White adipose tissue or white fat is one of the two types of adipose tissue found in mammals. The other kind is brown adipose tissue. White adipose tissue is composed of monolocular adipocytes. In humans, the healthy amount of white adipose t ...

, as were expression levels of a number of genes in the

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

metabolic pathway, including CerS2 and CerS4. CerS4 expression was also found to be elevated in the

brain The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head ( cephalization), usually near organs for special ...

of an Alzheimer's disease

mouse model A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...

References

{{reflist, 2 Human proteins Integral membrane proteins