Mutations in this enzyme are responsible for the wide range of defects present in SLOS. In another pathway leading to cholesterol synthesis, DHCR7 is required for the reduction of 7-Dehydrodesmosterol to desmosterol. Regulation
Regulation of cholesterol synthesis is complex and occurs primarily through the enzyme HMG-CoA reductase (catalyst of the rate-limiting step). It involves a feedback loop that is sensitive to cellular levels of cholesterol. The four main steps of regulation are:
The synthesis of the enzyme HMG-CoA reductase is controlled by sterol regulatory element binding protein (SREBP). This is a transcription factor that is inactive when cholesterol levels are high, and active when cholesterol levels are low. When cholesterol levels fall, SREBP is released from the nuclear membrane or endoplasmic reticulum, it then migrates to the nucleus and causes the transcription of the HMG-CoA reductase gene. The translation (creating the enzyme from the mRNA transcript) of HMG-CoA reductase is inhibited by derivatives of mevalonate and by dietary cholesterol. The degradation of HMG-CoA reductase is tightly controlled. The part of the enzyme that is bound to the endoplasmic reticulum senses signals, such as increased cholesterol levels, that lead to its degradation or proteolysis. When HMG-CoA reductase is phosphorylated, its activity decreases. This means cholesterol synthesis is reduced when cell energy (ATP) levels are low. Function
Cholesterol is an important lipid involved in metabolism, cell function, and structure. It is a structural component of the cell membrane, such that it provides structure and regulates the fluidity of the phospholipid bilayer. Furthermore, cholesterol is a constituent in lipid rafts.
Erythrokeratodermia variabilis (also known as "erythrokeratodermia figurata variabilis", "keratosis extremitatum progrediens", "keratosis palmoplantaris transgrediens et progrediens",: 509  "Mendes da Costa syndrome", "Mendes da Costa type erythrokeratodermia", and "progressive symmetric erythrokeratoderma") is a rare autosomal dominant disorder that usually presents at birth or during the first year of life. To date, it is thought to be caused by mutations in genes encoding for connexin channels proteins in the epidermis, leading to the misregulation of homeostasis in keratinocytes.One type is characterized by generalized, persistent, brown hyperkeratosis with accentuated skin markings, while a second type is localized, with involvement that is limited in extent and characterized by sharply demarcated, hyperkeratotic plaques. : 565 It can be associated with GJB3 and GJB4. It was characterized in 1925. See also
List of cutaneous conditions


== References ==