The structure of the DHCR7 rat gene is very similar to the structure of the human gene.The highest levels of DHCR7 expression have been detected in the adrenal gland, the testis, the liver and in brain tissue. Its expression is induced by decreased sterol concentrations via sterol regulatory binding proteins (SREBP). There is also evidence that its activity may be regulated by tissue specific transcription, and alternative splicing.As outlined above, the enzyme DHCR7 catalyzes the reduction of 7DHC to cholesterol, as well as the reduction of 7-dehydrodesmosterol to desmosterol. It requires NADPH as a cofactor for this reduction, and may involve the activity of cytochrome-P450 oxidoreductase. It is also thought to contain iron. DHCR7 is an integral membrane protein of the endoplasmic reticulum, and computer models have predicted up to nine transmembrane domains. DHCR7 is most efficient at reducing 7DHC, but it is known to reduce the carbon 7 double bond of other sterols, indicating a range of substrate specificity. The human version of this enzyme is predicted to have a molecular weight of 54,489 kDa, and an isoelectric point of 9.05.The amino acid sequence that encodes DHCR7 is predicted to contain 475 amino acids, as well as several protein motifs. It contains multiple sterol reductase motifs, as would be expected given its function. It contains a potential sterol-sensing domain (SSD), whose function is unknown but thought to be necessary for binding sterol substrates. It also includes multiple sites of phosphorylation, including potential protein kinase C and tyrosine kinase sites (regulatory enzymes responsible for phosphorylation).
For example, reduced levels of neurosteroids may be seen in SLOS. These are lipids which take part in signaling within the brain, and must be produced within the brain itself. They are responsible for interacting with nuclear steroid receptors, and bind to neurotransmitter-gated ion channels. Specifically, they modulate the effects of GABA and NMDA receptors, resulting in calming effects, improved memory, and more. Thus, given that some characteristics of SLOS are the opposite of these effects (hyperactivity, anxiety), a reduction in neurosteroids could influence both neurological development and behaviour. Furthermore, as outlined above, cholesterol is an important aspect in Hedgehog signaling. With lower levels of cholesterol, hedgehog proteins would not undergo the necessary covalent modification and subsequent activation. This would result in impaired embryonic development, and may contribute to the observed physical birth defects in SLOS. One particular hedgehog signaling protein, sonic hedgehog (SHH), is important in the pattern of the central nervous system, facial features, and limbs. Other hedgehog proteins may be involved in the development of the genital tract and the skeleton.The altered sterol levels in SLOS are particularly relevant to cell membranes, which are made primarily of lipids. SLOS patients may show cell membranes with abnormal properties or composition, and reduced cholesterol levels greatly affect the stability and proteins of lipid rafts. Despite their structural similarity, 7DHC is unable to replace cholesterol in lipid rafts. In addition, a lack of cholesterol contributes to the increased fluidity of the cell membrane, and may cause abnormal granule secretions.