CYP4F22 (cytochrome P450, family 4, subfamily F, polypeptide 22) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''CYP4F22''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. This gene encodes a member of the

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

superfamily of

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. The cytochrome P450 proteins are

monooxygenase Monooxygenases are enzymes that incorporate one hydroxyl group (−OH) into substrates in many metabolic pathways. In this reaction, the two atoms of dioxygen are reduced to one hydroxyl group and one H2O molecule by the concomitant oxidation of ...

s which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This gene is part of a cluster of cytochrome P450 genes on chromosome 19 and encodes an enzyme thought to play a role in the 12(R)-

lipoxygenase Lipoxygenases () (LOX) are a family of (non- heme) iron-containing enzymes, more specifically oxidative enzymes, most of which catalyze the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene into ce ...

pathway. Mutations in this gene are the cause of ichthyosis lamellar type 3.

Activity

CYP4F22, like other CYP4F proteins, is a Cytochrome P450 omega hydroxylase, i.e. an enzyme that metabolizes fatty acids to their omega

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...

derivatives (see

Omega oxidation Omega oxidation (ω-oxidation) is a process of fatty acid metabolism in some species of animals. It is an alternative pathway to beta oxidation In biochemistry and metabolism, beta oxidation (also β-oxidation) is the catabolic process by which fa ...

). This hydroxylation may: a) produce a biologically important signaling molecule such as occurs in the metabolism of 20-carbon straight chain

polyunsaturated fatty acid In biochemistry and nutrition, a polyunsaturated fat is a fat that contains a polyunsaturated fatty acid (abbreviated PUFA), which is a subclass of fatty acid characterized by a backbone with two or more carbon–carbon double bonds. Some polyunsa ...

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 ...

, to 20-Hydroxyeicosatetraenoic acid, b) inactivate a biologically important product such as the metabolism of the arachidonic acid metabolite, 5-oxo-eicosatetraenoic acid, to its ~100-fold less potent product, 5-oxo-20-hydroxy-eicosatetraenoic acid, or c) be the first step in the further metabolism of

xenobiotics A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...

or natural compounds CYP4F22 serves the latter function. It is a type 1

Integral membrane protein An integral, or intrinsic, membrane protein (IMP) is a type of membrane protein that is permanently attached to the biological membrane. All transmembrane proteins can be classified as IMPs, but not all IMPs are transmembrane proteins. IMPs comp ...

located 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 ...

of cells in the

stratum granulosum The stratum granulosum (or granular layer) is a thin layer of cells in the epidermis lying above the stratum spinosum and below the stratum corneum ( stratum lucidum on the soles and palms).James, William; Berger, Timothy; Elston, Dirk (2005) ''A ...

of mammalian, including human, skin where it functions to attach an omega hydroxyl residue to fatty acids that are exceptionally long, 28 or more carbons, i.e. the very long chain fatty acids (VLCFA). These VLCFA targets need not be free fatty acids but also can be acylated in an

amide bond In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent any group, typically organyl groups or hydrogen atoms. The amide group is called a p ...

sphingosine Sphingosine (2-amino-4-trans-octadecene-1,3-diol) is an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, which forms a primary part of sphingolipids, a class of cell membrane lipids that include sphingomyelin, an important phosphol ...

to form an acyl

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 ...

Function

CYP4F22 omega hydroxylates the VLCFA in esterified omega-oxyacyl-sphingosine complex to form an esterified omega-hydroxyacyl-sphingosine complex. This step is critical for delivering the

wax Waxes are a diverse class of organic compounds that are lipophilic, malleable solids near ambient temperatures. They include higher alkanes and lipids, typically with melting points above about 40 °C (104 °F), melting to give lo ...

-like, extremely

hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...

VLCFA to the

stratum corneum The stratum corneum (Latin language, Latin for 'horny layer') is the outermost layer of the epidermis (skin), epidermis. Consisting of dead tissue, it protects underlying tissue from infection, dehydration, chemicals and mechanical stress. It is ...

near the skin surface. It is these skin surface VLCFA which create and maintain the skin's ability to function as a water barrier. CYP4F22, like many of the CYP4F series of CYPs, may prove to serve other functions but its role in hydroxylating VLCFA in the skin's water barrier function, as defined in genetic studies (see below), has dominated research on it.

Genetic studies

A small number of newborns with

Congenital ichthyosiform erythroderma A birth defect is an abnormal condition that is present at birth, regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth ...

have been found to have autosomal recessive lose of function mutations in CYP4F22. Of the varies subtypes of congenital ichthyosiform erythroderma, these mutations have been associated almost exclusively with the

Lamellar ichthyosis Lamellar ichthyosis, also known as ichthyosis lamellaris and nonbullous congenital ichthyosis, is a rare inherited skin disorder, affecting around 1 in 600,000 people. Presentation Affected babies are born in a collodion membrane – a shiny, wa ...

subtype.

Activity

Function

Genetic studies

References

Further reading