Disease relevance of DESMOSTEROL

• The average increase in desmosterol was higher in intracerebral gliomas than in neurinomas of the trigeminal nerve [1].
• In this report we examine the macrophage ACAT reactivity of the shellfish sterol, desmosterol, and other sterols found in man because of shellfish ingestion or in association with the foam cell diseases sitosterolemia and cerebrotendinous xanthomatosis (CTX) [2].
• Desmosterol and delta 8-lathosterol were also identified in both the bile and the gallstones [3].
• Desmosterol in human and experimental brain tumors in tissue culture [4].
• Since desmosterol might substitute for cholesterol in neuronal membranes without detriment, the present study was undertaken to examine the possibility that this drug-induced epilepsy was related to changes in other brain lipids [5].

High impact information on DESMOSTEROL

• Steryl ester mass accumulation in desmosterol-treated human macrophages was 10-fold greater than in control cells and 3-fold greater than in cholesterol-treated cells [2].
• These data suggest that: (a) the shellfish sterols desmosterol and 24-methylene cholesterol may be atherogenic; and (b) the excessive foam cell formation seen in sitosterolemia and CTX cannot be explained by ACAT hyperreactivity of their associated sterols [2].
• Similarly, desmosterol increased only slightly in developing normal trigeminal nerve compared to the high levels observed in developing cerebrum [1].
• Desmosterol in rat central and peripheral nervous systems during normal and neoplastic growth [1].
• Desmosterol bound to purified LXRalpha and LXRbeta in vitro and supported the recruitment of steroid receptor coactivator 1 [6].

Chemical compound and disease context of DESMOSTEROL

• In dogs, a high incidence of severe cataracts with an early onset was induced by 20 and 40 mg/kg, po of 34-250 despite the lack of desmosterol or 7-dehydro-cholesterol in serum [7].
• We measured serum cholesterol precursors (squalene, delta 8-cholestenol, desmosterol, lathosterol, cholestanol) and plant sterols (campesterol, sitosterol, and avenasterol) from 11 patients (one man) with primary biliary cirrhosis (PBC) and 13 healthy women matched for age and weight [8].

Biological context of DESMOSTEROL

• SCP-2 overexpression also reduced high density lipoprotein-cholesterol secretion and apoA-I gene expression by 70% and doubled the rate of plasma membrane desmosterol conversion to cholesterol [9].
• These changes suggest that desmosterol and both n-3 and n-6 polyunsaturated fatty acids may have important roles in sexual maturation [10].
• In contrast, cholesterol precursors downstream from lanosterol, i.e., desmosterol and 7-dehydrocholesterol, completely replaced cholesterol in supporting NS-1 cell growth [11].
• 4. Location of this 3H label in the desmosterol showed that dealkylation of the clionasterol involved 3H migration from C-25 to C-24 [12].
• The large number of double bonds in DHA, six, and in desmosterol, two, may contribute to the membrane fluidity necessary for the motility of the sperm tails [13].

Anatomical context of DESMOSTEROL

• In astrocyte membranes, desmosterol and cholesterol were the predominant sterols [14].
• Unique lipids of primate spermatozoa: desmosterol and docosahexaenoic acid [15].
• Previously we demonstrated high concentrations of desmosterol and docosahexaenoic acid (DHA, 22:6 n-3) in monkey testes and sperm [13].
• In order to determine whether hydration of the delta 24 bond of desmosterol contributes to the formation of the regulatory oxysterol, 25-hydroxycholesterol, [3H]desmosterol was incubated with two cultured cell lines and the labeled products were analyzed [16].
• However, the main sterol synthesized in astrocytes was desmosterol, followed by lanosterol and cholesterol [17].

Associations of DESMOSTEROL with other chemical compounds

• The site of inhibition was determined to be distal to the formation of mevalonic acid since aphidicolin also inhibited the incorporation of [14C]mevalonolactone into desmosterol but had no effect on the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.34) or the incorporation of [14C]acetate into total nonsaponifiable lipids [18].
• An additional three oxysteroids, the 25,26-hydroxy derivatives of lanosterol, zymosterol, and desmosterol, respectively, were generated in vitro by CYP27A1-transfected bacteria [19].
• The inhibition of sterol (24)-reductase was confirmed in rat liver microsomes by using (14)C-labelled desmosterol as the substrate [20].
• In lanosterol- and desmosterol-containing membranes, the DPPC and sterol diffusion coefficients are somewhat higher [21].
• Fasting insulin correlated with desmosterol (r = 0.286, P = 0.015) and lathosterol (r = 0.248, P = 0.037) even when the rates of WBGU and body mass index (BMI) were controlled for [22].

Gene context of DESMOSTEROL

• Both parents had mildly increased levels of desmosterol in plasma (mother: 1.4 mcg/ml; father: 1.8 mcg/ml), consistent with heterozygosity for DHCR24 deficiency [23].
• In brain, levels of cholesterol, desmosterol and 7-dehydrodesmosterol are reduced in shiverer and quaking, but not in trembler 60-day-old dysmyelinating mutant mice [24].
• A CH25H enzyme inhibitor, desmosterol, increases basal cell number but has no significant effect on vitamin D3 treated cells [25].
• DHCR7 deficiency impairs both cholesterol and desmosterol production, resulting in elevated 7DHC/8DHC levels, typically decreased cholesterol levels and, importantly, developmental dysmorphology [26].
• Michaelis-Menten kinetics are observed with DHA which has an apparent Km of 32 microM, while desmosterol inhibits sulfotransferase activity at high concentrations [27].

Analytical, diagnostic and therapeutic context of DESMOSTEROL

• This inhibition was accompanied by an accumulation of radioactivity in an intermediate which coeluted with authentic desmosterol upon high performance liquid chromatography (HPLC) [28].
• Oxygenation of desmosterol occurred in both Dede and L cell cultures to give a mixture of 24(R)- and 24(S)-25-epoxy-cholesterol [16].
• Comparison of the animal model with human syndromes, including limb osseous and skeleton perturbations, suggests a combination of desmosterol and Delta8 unsaturated sterols as being involved in the deleterious influence on limb bone formation [29].
• Sperm DHA concentration was positively correlated to sperm motility, to sperm count, and to the desmosterol-to-cholesterol ratio [30].
• Identification of desmosterol was based on retention times with two gas liquid chromatography (GLC) columns and verified by GC-mass spectrometry [31].

References