In the final step of cholesterol synthesis, 7-dehydrocholesterol reductase (DHCR7) reduces the double bond at C7-8 of 7-dehydrocholesterol to yield cholesterol. Mutations of DHCR7 cause Smith-Lemli-Opitz syndrome (SLOS). Over 100 different mutations of DHCR7 have been identified in SLOS patients. SLOS is a classical multiple malformation, mental retardation syndrome, and was the first human malformation syndrome shown to result from an inborn error of cholesterol synthesis. This paper reviews the biochemical, molecular, and mutational aspects of DHCR7.
If the enzyme encoded by HSD11 is not responsible for 11β-hydroxysteroid dehydrogenase activity in the distal renal tubule, what then is its physiological function? This enzyme is present at very high levels in human liver, the main site of cortisone reduction, so it may function primarily as a reductase in vivo . Because HSD11 is widely expressed, it has also been suggested that the encoded enzyme functions to protect the glucocorticoid (Type II) receptor in various tissues from excessive concentrations of cortisol ( Whorwood et al ., 1992, 1993 ).