CYP27C1

CYP27C1 (cytochrome P450, family 27, subfamily C, polypeptide 1) is a protein that in humans is encoded by the ''CYP27C1'' gene. The Enzyme Commission number (EC) for this protein is EC 1.14.19.53. The full accepted name is ''all-trans-''retinol 3,4-desaturase and the EC number 1 classifies CYP27C1 as a oxidoreductase that acts on paired donor by reducing oxygen. It is also identifiable by the UniProt code Q4G0S4.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids.

The main function of the CYP27C1 enzyme is conversion of vitamin A₁ (all-''trans'' retinol) to vitamin A₂ (all-''trans'' 3,4-dehydroretinal).

Activity

The basic reaction for CYP27C1 is as follows:

:''all-trans''-retinol + 2 reduced adrenodoxin + 2 H⁺ + O₂ = ''all-trans''-3,4-didehydroretinol + 2 oxidized adrenodoxin + 2 H₂O.

The initial substrate for this reaction is ordinary retinol, which can come from a number of vitamers all known as vitamin A.

The catalytic efficiency of CYP27C1 was assessed for all ''trans''-retinol, retinal, and retinoic acid, and was highest for retinol, indicating that this enzyme is primed to convert vitamin A₁ to A₂. It does also convert all ''trans'' retinal, retinoic acid, and 11-''cis'' retinal.

Regulation

Thyroid hormones (TH) may play a role in inducing this change, as TH receptors have been shown to regulate CYP27C1 within the retinal pigment epithelium. TH nuclear receptors ''thraa^-I-'', ''thrab^-I-'', and ''thrb^-I-'' were needed for the successful conversion of vitamin A, however, no one receptor was identified as being absolutely necessary.

Structure

CYP27C1 is predicted to have many alpha helices and to be globular in shape. It is unclear where the active site lies in the protein, but there is a low confidence loop region that would be able to fit a molecule of retinol.

Function in humans

CYP27C1 catalyzes 3,4-desaturation of retinoids, particularly all-''trans''-retinol (vitamin A₁) to all-''trans'' 3,4-dehydroretinal (vitamin A₂). The enzyme is unusual among mammalian P450s in that the predominant oxidation is a desaturation and in that hydroxylation represents only a minor pathway - the enzyme catalyzes 3- and 4-hydroxylation as minor events. The enzyme is located in human skin epidermis.

The function of the enzyme was only discovered in 2016. Before that, it was considered an "orphan" enzyme. An orphan enzyme is an enzyme activity that has been experimentally characterized but for which there is no known amino-acid or nucleotide sequence data.

One of the functions in humans also involves negatively regulating lung cancer cell proliferation by means of regulating the IGF-1R/Akt/p53 signaling pathways. Researches found that CYP27C1 knock-downs in mice led to increased tumor cell proliferation, colony formation, and tumor burden. Vinorelbine, a chemotherapy drug used to treat lung cancer, could potentially be a novel substrate for CYP27C1.

Function in fish

Despite being found in human skin, CYP27C1 is also found in other mammals, birds, fish and amphibians. CYP27C1 is responsible for shifting photosensitivity by converting vitamin A₁ to vitamin A₂ in the rhodopsin in fish eyes. In zebrafish and lamprey, CYP27C1 is expressed in the retinal pigment epithelium. The replacement of A₁ by A₂ broadens the range of the spectral absorption bandwidth and shifts the sensitivity towards red. This conversion also decreases photosensitivity.

In Pacific salmonids in particular, Coho salmon parr shift vitamin A₁/A₂ ratio in their rod visual pigments in accordance with temperature and day length. A₂ increases during winter and decreases in summer. The increased density ofA₂ in winter may reduce the parr's ability to see and respond to near-infrared light, as occurs in zebrafish, when there is less light availability. The seasonal differences in retinal expression in rods are indicative of plasticity in spectral scope driven by environmental conditions.

Similar shifts in vitamin A₁ to A₂ along with increased CYP7C1 expression in juvenile lampreys indicate that red-shifted vision is an ancestrally evolved mechanism that helped fish adapt to different spectral climates during ontogeny. Differences in expression of CYP27C1 in the same species of lamprey in different areas further support that CYP27C1 is used in sensory plasticity and offer insights into the evolutionary history of the function of CYP27C1.

Recently, the gene sequence for CYP27C1 has been isolated, as least in goldfish.This gene is 540 amino acids long in ''Carassius auratus'' and has a GenBank reference number of XP-026113677.1. This length is similar to other CYP reductases and is an average length for a protein.

Popular culture

CYP27C1 is the topic of the comic Sherman's lagoon for May 26, 2016. In response to Hawthorne's inquiry about the chemical, Ernest explains that it is an enzyme that enhances ability to see infrared light, allowing fish to see better in murky waters. Ernest can see however that Hawthorne is more interested in how to synthesize it commercially.

References

Further reading

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External links

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{{Cytochrome P450
Cytochrome P450