Disorders of Sterol Metabolism
A number of disorders are now associated with various defects in the biosynthesis of cholesterol. Many of these were first described as dysmorphic syndromes before the underlying biochemical abnormality was identified. The prototype disorder is Smith-Lemli-Opitz syndrome.
Infants with Smith-Lemli-Optiz syndrome have a defect in the sonic hedgehog gene (Fig. 1.61). This gene is involved in limb formation and cholesterol biosynthesis. The biochemical error is a block in the final step of cholesterol formation, with deficiency of cholesterol and accumulation of the precursor 7-dehydrocholesterol. Typical dysmorphic features include upturned nose, low-set ears, and characteristic clenched hands. Affected patients typically have syndactyly of the second and third toes, and they can have polydactyly, presumably a direct effect of the gene defect. Some phenotypic findings, such as undervirilization of males, are attributable to cholesterol deficiency causing deficiency of cholesterol-based steroid hormones. In some cases, CNS findings improve with cholesterol supplementation.
There are a number of other disorders in other steps in cholesterol biosynthesis that have various physical and developmental findings. X-linked dominant chondrodysplasia punctata (Conradi-Hünermann-Happle syndrome) is believed lethal in males and is associated with mutations in sterol isomerase (emopamil-binding protein; EBP) in females. This results in elevated levels of 8-dehydrocholesterol and 8(9)-cholesterol. Findings include chondrodysplasia punctata, asymmetric limb shortening, scoliosis, and scaly erythematous rash along the lines of Blaschko in infancy that can change into ichthyosis, scarring alopecia, and pigmentary abnormalities.
FATS | Classification
M.H. Gordon, in Encyclopedia of Food Sciences and Nutrition (Second Edition), 2003
Sterols occur in the membranes of plants, animals, and microorganisms and are termed phytosterols, zoosterols, and mycosterols, respectively. Cholesterol is the main zoosterol, but sterols in plants commonly occur as mixtures with β-sitosterol, campesterol, and stigmasterol representing three of the major phytosterols. These sterols are all Δ5-sterols (Figure 6), but Δ7-sterols may also be present in small quantities (Table 1). Molecules with a sterol-type structure that lack an endocyclic double bond are termed sterols. Methyl sterols, also known as triterpenyl alcohol, have an additional methyl group at carbon-4 in the A-ring of the molecule. Methyl sterols and dimethylsterols commonly occur with sterols in plant membranes. Bacteria usually lack sterols in their membranes, but yeasts accumulate considerable quantities of sterols, which may represent up to 10% of the cellular dry weight. Algae produce a wide variety of sterols. (See CHOLESTEROL | Properties and Determination.)
Figure 6. Sterol structure. Reproduced from Lipids, Encyclopaedia of Food Science, Food Technology and Nutrition, Macrae R, Robinson RK and Sadler MJ (eds), 1993, Academic Press.
Total sterols (%)Composition (%)aIIIIIIIVVVIVIIVIIIIXX
Data from Itoh T, Tamura T and Matsumoto T (1973) Sterol composition of 19 vegetable oils. Journal of the American Oil Chemists' Society 50: 122–125.β