Cholestnol is a physiological sterol in animals, but occurs in far lower concentrations than does cholesterol. The chemical structure of cholestanol resembles that of cholesterol, missing only a double bond at the 5-6 position of the B-ring. The large difference in these concentrations has made it difficult to investigate the role of cholestanol in the body. The accumulation of cholestanol was reported by Menkes in CTX patients, which suggested a pathological role of cholestanol in reverse of its physiological function.
Figure 1. Three-dimensional structures of cholesterol (upper) and cholestanol (lower).
Cholestanol is a physiological substance that is synthesized in the body from cholesterol with 4-cholesten-3-one as an intermediate, and exists universally at the concentration of 1/500 to 1/800 of cholesterol. The absence of sterol 27-hydroxylase activity in CTX patients increases the flow of substrate through the minor route from 7a-hydroxy-4-cholesten-3-one (pathway c) to 4-cholesten-3-one (pathway a) through cholesta-4,6-dien-3-one.
Figure 2. Metabolic pathway of cholesterol to bile acid and cholestanol.
The similarity in structure with cholesterol and low concentrations has caused cholestanol to go largely unnoticed. However, in the hereditary disease cerebrotendinous xanthomatosis (CTX), cholestanol deposition causes several symptoms. Tendon xanthomas, cerebellar ataxia, pyramidal sign, cataracts, and mental retardation were the reported symptoms, but few patients developed all of the symptoms, making a consistent diagnosis difficult. Therefore, a biochemical diagnosis was needed to provide objective diagnostic criteria for the hereditary disease. Initially scientists used cholestanol concentrations in serum as the diagnostic criteria, but now another method is to demonstrate the lack of mitochondrial sterol 27-hydroxylase activities. In addition, incomplete oxidation of the cholesterol side chain leads to excretion of large amounts of C27-bile alcohols in bile, feces, and urine. Detection of such abnormal bile alcohols is also helpful for the diagnosis of CTX.
The low concentrations and structural similarity to cholesterol have made it difficult to separate and analyze cholestanol in biological specimens. Because of its accuracy and specificity, we developed a high-performance liquid chromatography (HPLC) assay for the quantitative analysis of cholestanol.
With integrated set of separation, characterization, identification and quantification systems featured with excellent robustness & reproducibility, high and ultra-sensitivity, Creative Proteomics provides reliable, rapid and cost-effective cholestanol targeted metabolomics services.
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