| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Lipoproteins do not influence cholesterol synthesis in freshly isolated rat hepatocytes, cautionary note Geelen, M. J., A. C. Beynen, et al. (1991), Int J Biochem 23(3): 347-51. Abstract: 1. Suspensions of freshly isolated rat hepatocytes were used to study the effects of native and derivatized lipoproteins on the rate of cholesterogenesis. 2. Short-term incubation of the hepatocytes with a variety of lipoproteins failed to modify the rate of cholesterol synthesis as determined by the incorporation of tritium from tritiated water into cholesterol after separation from other lipids by thin-layer chromatography. 3. Neither an increase in the cholesterol content of the particles (beta-very-low-density lipoproteins) nor derivatization of the lipoproteins (lactosylated-low-density lipoproteins or high-density lipoproteins associated with a tris-galactoside-terminated cholesterol derivative) nor cholesterol-containing liposomes were effective in this respect. 4. Whether this behaviour represents an artefact of the isolated hepatocyte preparation is unknown yet. |
| Lipoproteins in familial dysbetalipoproteinemia. Variation of serum cholesterol level associated with VLDL concentration Zhao, S. P., A. H. Smelt, et al. (1993), Arterioscler Thromb 13(2): 316-23. Abstract: Patients with familial dysbetalipoproteinemia (FD) associated with the apo E2/2 phenotype exhibit a marked interindividual variability in serum cholesterol and triglyceride concentrations. It has been proposed that this variability is due to a combination of the apo E2/2 phenotype and additional genetic factors implicated in diseases like familial hypercholesterolemia, familial combined hyperlipoproteinemia, and familial hypertriglyceridemia. To further explore the nature of this variability, the lipoprotein profiles of 17 patients with FD associated with the apo E2/2 phenotype were analyzed by a density-gradient ultracentrifugation technique and by 2-16% polyacrylamide gel electrophoresis. It was found that all patients with FD were characterized by 1) markedly increased cholesterol concentrations of large very low density lipoprotein (VLDL) (VLDL1) (2.98 +/- 3.08 versus 0.08 +/- 0.03 mmol/L), small VLDL (VLDL2) (4.68 +/- 1.93 versus 0.27 +/- 0.13 mmol/L), and intermediate density lipoprotein (IDL) (2.25 +/- 0.72 versus 0.39 +/- 0.16 mmol/L); 2) decreased low density lipoprotein (LDL) cholesterol level (1.84 +/- 0.54 versus 3.36 +/- 0.53 mmol/L); and 3) altered composition (enrichment by cholesteryl ester) of VLDL1 and VLDL2 compared with normolipidemic control subjects. The cholesterol levels of IDL and LDL showed minor interindividual variabilities and were not correlated with serum cholesterol and triglyceride levels. The compositions of VLDL1 and VLDL2 were independent of the concentrations of lipids in serum. However, the cholesterol concentrations of VLDL1 and VLDL2 showed considerable interindividual variabilities and were positively correlated with the serum cholesterol concentration (r = 0.84 and r = 0.95, respectively, both p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) |
| Lipoproteins in interstitial fluid of dogs: implications for a role in reverse cholesterol transport Roheim, P. S., L. Dory, et al. (1990), Eur Heart J 11 Suppl E: 225-9. |
| Liposomal hamycin in the control of experimental aspergillosis in mice: effect of phosphatidic acid with and without cholesterol Moonis, M., I. Ahmad, et al. (1993), J Antimicrob Chemother 31(4): 569-79. Abstract: Hamycin incorporated into liposomes containing phosphatidylcholine (SPC) and phosphatidic acid (PA) had reduced toxicity and an enhanced antifungal activity in experimental aspergillosis in balb/c mice. Incorporation of cholesterol into liposomes led to a dose dependent decrease in the toxicity of hamycin. The LD50 (mg/kg) of hamycin contained in SPC/cholesterol/PA (molar ratio 4:5:1) liposomes was 2.8 whereas that in SPC/PA liposomes (molar ratio 9:1) was 0.35. Although the free drug had little or no protective effect on the animals, those administered liposomal hamycin at an equivalent dose (0.1 mg/kg) in the absence of cholesterol (SPC/PA; molar ratio 9:1) showed 90% survival after seven days of therapy. On the other hand the presence of cholesterol in the carrier phosphatidic acid liposomes (SPC/cholesterol/PA; molar ratio 4:5:1) at a similar dose (0.1 mg/kg) led to a 60% survival over the same time period. Hamycin incorporation in phosphatidic acid liposomes both in the presence or absence of cholesterol was found to be effective in reducing the fungal load in lung, liver, spleen and kidney. Studies with distribution of hamycin in various tissues by HPLC showed a significant reduction in the concentration of the liposomal drug in circulation as compared to those seem after administration of free drug. |
| Liquid-crystalline phases of cholesterol/lipid bilayers as revealed by the fluorescence of trans-parinaric acid Reyes Mateo, C., A. Ulises Acuna, et al. (1995), Biophys J 68(3): 978-87. Abstract: The presence of two liquid-crystalline phases, alpha and beta, in mixed bilayers of dimyristoylphosphatidylcholine/cholesterol was detected by the changes in the distribution of the fluorescence lifetimes of t-PnA, as analyzed by the Maximum Entropy Method. The formation of the liquid-ordered beta-phase, in the 30-40 degrees C temperature range as a function of cholesterol concentration (0-40 mol%), could be related quantitatively to the relative amplitude of a long lifetime component of the probe (10-14 ns). Based on this evidence, the phase behavior of mixtures of the unsaturated lipid palmitoyloleoylphosphatidylcholine and cholesterol was determined using the same technique, for cholesterol concentrations in the 0-50 mol% range, between 10 and 40 degrees C. It was found that two liquid-crystalline phases are also formed in this system, with physical properties reminiscent of the alpha- and beta-phases formed with saturated lipids. However, in this case it was determined that, for temperatures in the physiological range, the alpha- and beta-phases coexist up to 40 mol% cholesterol. This finding may be of significant biological relevance, because it supports the long held notion that cholesterol is responsible for the lipid packing heterogeneity of several natural membranes rich in unsaturated lipid components. |
| LISREL modeling of high density lipoprotein cholesterol (HDL) levels in male twins Schwartz, J. E., H. Yuan, et al. (1993), Genet Epidemiol 10(6): 545-9. Abstract: Based on the LISREL modeling approach for data from monozygotic (MZ) and dizygotic (DZ) twins Heath et al., 1989; Neale and Cardon, 1992, the hypothesized variance of the logarithm of high density lipoprotein cholesterol due to additive genetic factors was estimated to equal 19% for males. Unobserved common environment accounted for 32% of the variance of log HDL. Both estimates controlled for body mass, alcohol consumption, and smoking. The model had very strong goodness-of-fit indices. |
| Listeriolysin O: cholesterol inhibits cytolysis but not binding to cellular membranes Jacobs, T., A. Darji, et al. (1998), Mol Microbiol 28(6): 1081-9. Abstract: Listeriolysin O (LLO) binds to cholesterol-containing membranes in which it oligomerizes to form pores. Preincubation of the toxin with cholesterol is known to inhibit haemolysis, whereas the oxidized form of cholesterol has no inhibitory effect. Using immunoblot analyses and flow cytometry we demonstrate that preincubation with cholesterol does not influence binding of the listeriolysin-cholesterol complex to red blood cells, eukaryotic cells or artificial membranes. Lytic activity of membrane-bound LLO inactivated by cholesterol can be restored by enzymatic treatment with cholesterol oxidase. To determine the step at which cholesterol inhibits lytic activity, we looked for pore formation using electron microscopy. Pores formed by purified listeriolysin could be directly visualized using erythrocyte ghosts. This property was lost upon incubation of the toxin with cholesterol. Quantitative analysis strongly suggest that inhibition of lysis by cholesterol is not due to decreased binding of listeriolysin to target membranes, but rather to an interference with a subsequent step leading to polymerization of the toxin. |
| Lith genes control mucin accumulation, cholesterol crystallization, and gallstone formation in A/J and AKR/J inbred mice Lammert, F., D. Q. Wang, et al. (2002), Hepatology 36(5): 1145-54. Abstract: We recently identified 2 Lith genes that determine cholesterol gallstone formation in C57L/J inbred mice, which show a gallstone prevalence of approximately 80% on feeding 1.0% cholesterol and 0.5% cholic acid. The aim of this study was to explore if the same Lith loci contribute to the variation in gallstone susceptibility in a new experimental cross. After 12 weeks of feeding the lithogenic diet to inbred mice of strains A/J and AKR/J as well as their F(1) progeny, we used microscopy of bile to assess mucin accumulation, crystallization pathways, and stone formation. Backcross progeny (n = 225) were phenotyped and genotyped selectively for microsatellite markers spanning the genome. Quantitative trait loci (QTL) affecting gallstone phenotypes were identified by linkage analysis. Both inbred strains showed accumulation of mucin gel and cholesterol supersaturation. However, only strain AKR developed gallstones (prevalence of 20%), whereas strain A showed a stable liquid crystalline state and no stones. QTL analysis identified a gallstone locus on chromosome 17 (Lith3). A second gene locus on chromosome 15 that controls mucin accumulation harbors the mucin gene Glycam1, which was shown to be expressed in gallbladder epithelia by immunohistochemistry. Gallstone and mucin loci colocalized with potential QTLs affecting the formation of cholesterol crystals. In conclusion, QTL analysis identified specific gene loci determining mucin accumulation, cholesterol crystallization, and gallstone formation. Characterization of the pathophysiologic roles of Lith3 and the new biliary mucin gene Glycam1 might provide insights into primary defects of human cholelithiasis and lead to new therapeutic strategies for prestone intervention. |
| Lith1, a major gene affecting cholesterol gallstone formation among inbred strains of mice Khanuja, B., Y. C. Cheah, et al. (1995), Proc Natl Acad Sci U S A 92(17): 7729-33. Abstract: The prevalence of cholesterol gallstones differs among inbred strains of mice fed a diet containing 15% (wt/wt) dairy fat, 1% (wt/wt) cholesterol, and 0.5% (wt/wt) cholic acid. Strains C57L, SWR, and A were notable for a high prevalence of cholelithiasis; strains C57BL/6, C3H, and SJL had an intermediate prevalence; and strains SM, AKR, and DBA/2 exhibited no cholelithiasis after consuming the diet for 18 weeks. Genetic analysis of the difference in gallstone prevalence rates between strains AKR and C57L was carried out by using the AKXL recombinant inbred strain set and (AKR x C57L)F1 x AKR backcross mice. Susceptibility to gallstone formation was found to be a dominant trait determined by at least two genes. A major gene, named Lith1, mapped to mouse chromosome 2. When examined after 6 weeks on the lithogenic diet, the activity of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (EC 1.1.1.88) was downregulated as expected in the gallstone-resistant strains, AKR and SJL, but this enzyme failed to downregulate in C57L and SWR, the gallstone-susceptible strains. This suggests that regulation of the rate-limiting enzyme in cholesterol biosynthesis may be pivotal in determining the occurrence and severity of cholesterol hypersecretion and hence lithogenicity of gallbladder bile. These studies indicate that genetic factors are critical in determining gallstone formation and that the genetic resources of the mouse model may permit these factors to be identified. |
| Lith6: a new QTL for cholesterol gallstones from an intercross of CAST/Ei and DBA/2J inbred mouse strains Lyons, M. A., H. Wittenburg, et al. (2003), J Lipid Res 44(9): 1763-71. Abstract: A complex genetic basis determines the individual predisposition to develop cholesterol gallstones in response to environmental factors. We employed quantitative trait locus/loci (QTL) analyses of an intercross between inbred strains CAST/Ei (susceptible) and DBA/2J (resistant) to determine the subset of gallstone susceptibility (Lith) genes these strains possess. Parental and first filial generation mice of both genders and male intercross offspring were evaluated for gallstone formation after feeding a lithogenic diet. Linkage analysis was performed using a form of multiple interval mapping. One significant QTL colocalized with Lith1 chromosome (chr) 2, 50 cM, a locus identified previously. Significantly, new QTL were detected and named Lith10 (chr 6, 4 cM), Lith6 (chr 6, 54 cM), and Lith11 (chr 8, 58 cM). Statistical and genetic analyses suggest that Lith6 comprises two QTL in close proximity. Our molecular and genetic data support the candidacy of peroxisome proliferator-activated receptor gamma (Pparg) and Slc21a1, encoding Pparg, and the basolateral bile acid transporter SLC21A1 (Slc21a1/Oatp1), respectively, as genes underlying Lith6. |
| Lithogenic diet and gallstone formation in mice: integrated response of activities of regulatory enzymes in hepatic cholesterol metabolism Reihner, E. and D. Stahlberg (1996), Br J Nutr 76(5): 765-72. Abstract: Supersaturation of bile with cholesterol is a prerequisite of the development of gallstones. With the intention to study the integrated response of enzymes regulating hepatic cholesterol metabolism during gallstone formation we used an established model for the induction of cholesterol gallstone disease in mice. Ten mice were fed on a lithogenic diet containing 10 g cholesterol/kg and 5 g cholic acid/kg for 8 weeks and were compared with ten mice fed on a standard pellet diet. Cholesterol crystals or gallstones developed in 90% of gallbladders in treated mice. The lithogenic diet had an inhibitory effect on the rate-limiting enzyme of cholesterol biosynthesis, hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (EC 1.1.1.88) activity, 39.6 (SEM 2.8) v. 171.0 (SEM 47.3) pmol/min per mg protein. Cholesterol 7 alpha-hydroxylase (EC 1.14.13.17) activity, regulating bile acid synthesis, was decreased by 80%, and this was assumed to be due to cholic acid in the diet. The cholesterol-enriched diet also induced a tenfold increase in cholesterol esterification rate in the liver, i.e. acyl-CoA:cholesterol acyl transferase (ACAT; EC 2.3.1.26) activity. The total, as well as esterified, cholesterol contents of liver homogenates were significantly higher in cholesterol- and cholic acid-treated mice and correlated well with the ACAT activity (rs 0.72 (P < 0.005), and rs 0.68 (P < 0.01) respectively). A significantly higher ACAT activity was obtained in mice given cholesterol and cholic acid even when the enzyme was saturated with exogenous cholesterol, thus indicating an increased amount of the enzyme. The formation of gallstones is dependent on a delicate balance between lithogenic factors (increased absorption of cholesterol and reduced secretion of bile acids) and defence mechanisms (decreased synthesis and increased esterification of cholesterol). In the specific animal model studied here the two defence mechanisms cannot compensate for the increased absorption of cholesterol and the reduced synthesis of bile acids. |
| Lithotripsy plus ursodiol is superior to ursodiol alone for cholesterol gallstones Tint, G. S., H. Dyrszka, et al. (1992), Gastroenterology 102(6): 2042-9. Abstract: The safety and efficacy of gallbladder extracorporeal shock-wave lithotripsy combined with 600 mg/day ursodiol were examined in 85 patients with radiolucent gallstones, 15 with lightly calcified gallstones, and 12 with radiolucent stones pretreated for greater than or equal to 2 months with 600 mg/day ursodiol. Results were compared with those of a well-matched lithotripsy-eligible group of 32 subjects treated with ursodiol alone (no lithotripsy). Pretreatment with ursodiol significantly improved while gallstone calcification interfered with fragmentation. Small gallstone size and number also aided fragmentation. Biliary lithotripsy plus ursodiol increased efficacy twofold compared with ursodiol therapy alone (47% vs. 22% of subjects gallstone free; P less than 0.02). Gallstones did not disappear in any subject with calcified gallstones (P less than 0.001) vs. lithotripsy). Product-limit analysis showed that the efficacy for gallstone dissolution increases in the following order: ursodiol alone, lithotripsy-ursodiol, lithotripsy-ursodiol pretreated with ursodiol (P less than 0.02, pairwise). Similar mean gallstone-dissolution rate constants (stone size divided by time to disappear) of stone fragments and whole gallstones during ursodiol therapy suggest that most fragments disappear by dissolution not expulsion. This finding explains why fragmentation appears to be the key predictor of disappearance and even partial fragmentation accelerates gallstone clearance. |
| Liver cholesterol concentrations in rats fed diets containing various fats of plant origin Zhang, X. Z., G. W. Meijer, et al. (1990), Int J Vitam Nutr Res 60(3): 275-8. Abstract: Plasma and liver cholesterol concentrations were measured in rats fed high-cholesterol (1%, w/w), semipurified diets containing various fats of plant origin. Palm oil produced significantly higher plasma cholesterol concentrations than soybean oil, rapeseed oil, coconut fat and palm kernel oil. The content of liver cholesterol in rats fed rapeseed oil was significantly higher than in rats fed the other fats except for soybean oil. When comparing the fatty acid compositions of the fats used, this study suggests that oleic acid induces higher liver cholesterol concentrations than linoleic acid. |
| Liver copper content of rats hypo- or hyperresponsive to dietary cholesterol de Wolf, I., X. Fielmich-Bouman, et al. (2003), J Trace Elem Med Biol 17(3): 177-82. Abstract: The question addressed is whether cholesterol intake reduces the hepatic copper content in rats. For this purpose we have compared the hepatic copper content of two selected rat inbred strains after feeding the animals a control or a high fat, high cholesterol diet. One strain was dietary cholesterol resistant (SHR/OlaIpcv), whereas the other strain was susceptible to dietary cholesterol (BN-Lx/Cub). Dietary cholesterol-susceptible rats have a lower baseline hepatic copper content when compared with their resistant counterparts. The consumption of a hypercholesterolemic diet decreased the liver copper concentration (expressed in microg/g dry weight) to about the same extent in both strains. However, dietary cholesterol did not reduce the absolute (expressed as microg/whole liver) and relative (expressed as microg/whole liver/100 g body weight) copper store of rats. The decrease of liver copper concentration after the high fat, high cholesterol diet is probably not caused by a decrease in whole hepatic copper content, but rather due to dietary-induced hepatomegaly. |
| Liver damage and protective effect of high density lipoprotein cholesterol Salonen, J. T. (2003), Bmj 327(7423): 1082-3. |
| Liver disease with altered bile acid transport in Niemann-Pick C mice on a high-fat, 1% cholesterol diet Erickson, R. P., A. Bhattacharyya, et al. (2005), Am J Physiol Gastrointest Liver Physiol 289(2): G300-7. Abstract: Cholestatic hepatitis is frequently found in Niemann-Pick C (NPC) disease. We studied the influence of diet and the low density lipoprotein receptor (LDLR, Ldlr in mice, known to be the source of most of the stored cholesterol) on liver disease in the mouse model of NPC. Npc1-/- mice of both sexes, with or without the Ldlr knockout, were fed a 18% fat, 1% cholesterol ("high-fat") diet and were evaluated by chemical and histological methods. Bile acid transporters multidrug resistance protein (Mrps) 1-5; Ntcp, Bsep, and OatP1, 2, and 4 were quantitated by real-time RT-PCR. Many mice died prematurely (within 6 wk) with hepatomegaly. Histopathology showed an increase in macrophage and hepatocyte lipids independent of Ldlr genotype. Non-zone-dependent diffuse fibrosis was found in the surviving mice. Serum alanine aminotransferase was elevated in Npc1-/- mice on the regular diet and frequently became markedly elevated with the high-fat diet. Serum cholesterol was increased in the controls but not the Npc1-/- mice on the high-fat diet; it was massively increased in the Ldlr-/- mice. Esterified cholesterol was greatly increased by the high-fat diet, independent of Ldlr genotype. gamma-Glutamyltransferase was also elevated in Npc1-/- mice, more so on the high-fat diet. Mrps 1-5 were elevated in Npc1-/- liver and became more elevated with the high-fat diet; Ntcp, Bsep, and OatP2 were elevated in Npc1-/- liver and were suppressed by the high-fat diet. In conclusion, Npc1-/- mice on a high-fat diet provide an animal model of NPC cholestatic hepatitis and indicate a role for altered bile acid transport in its pathogenesis. |
| Liver function and the level of total cholesterol in the blood serum in liver cirrhosis Komorovs'kyi, R. R. (1998), Lik Sprava(8): 83-5. Abstract: The authors have analyzed findings from a laboratory examination of 50 subjects presenting with different affections of the liver. Correlation is established between the level of total cholesterol and activity of alanine aminotransferase in blood serum of cirrhotic patients, it being particularly clear in portal cirrhosis (r = -0.85; P < 0.05), as well as significantly higher levels of total and indirect bilirubin and lower level of albumins in patients presenting with a reduced level of total cholesterol. This allows the decrease in the blood serum content of total cholesterol to be regarded as an unfavourable index in hepatocirrhosis. |
| Liver metabolism of cholesterol taken up from lipoproteins in Wistar rats. An in vivo comparison between rat and human lipoproteins Bravo, E. and A. Cantafora (1992), Comp Biochem Physiol B 101(4): 637-43. Abstract: 1. This study compares liver uptake, biliary secretion and blood decay of VLDL, LDL, HDL2 and HDL3 lipoprotein fractions isolated from both rat and human plasma and labelled with 14C-cholesterol following the i.v. administration to the bile-fistulated rat model. 2. The present results demonstrate that the use of heterologous lipoproteins in bile-fistulated rat can be helpful in administering in a small volume large amounts of free and esterified cholesterol and in evaluating specific aspects of lipoprotein cholesterol metabolism by liver. |
| Liver mevalonate 5-pyrophosphate decarboxylase is responsible for reduced serum cholesterol in stroke-prone spontaneously hypertensive rat Sawamura, M., Y. Nara, et al. (1992), J Biol Chem 267(9): 6051-5. Abstract: Spontaneously hypertensive rat (stroke-prone) (SHRSP) has an interestingly low serum cholesterol level due to a reduced biosynthesis of cholesterol in the liver (Iritani, N., Fukuda, E., Nara, Y., and Yamori, Y. (1977) Atherosclerosis 28, 217-222). In this study, we examined the mechanism underlying the reduction of hepatic cholesterol biosynthesis in the rat. Our initial findings in SHRSP, as compared with normotensive Wistar Kyoto rat (WKY), showed that 1) the incorporation of 14Cacetate into cholesterol in the liver slices was markedly less, 2) 3-hydroxyl-3-methylglutaryl (HMG) CoA reductase activity was not reduced, and 3) the incorporation of 3Hmevalonic acid into both cholesterol and squalene was significantly less. The above initial findings suggested that the reduction in the hepatic cholesterol biosynthesis took place in one or more enzymatic processes starting with mevalonic acid and continuing to squalene. When the incorporation of 3Hmevalonic acid into phosphomevalonate derivatives was studied using an ion exchange column, only the radioactivity incorporated into isopentenyl-pyrophosphate (isopentenyl-PP) was less in SHRSP. Furthermore, the specific activity of diphosphomevalonate (mevalonate-PP) decarboxylase in the liver-soluble fractions was reduced 50% in SHRSP as compared with WKY. Kinetic studies using liver crude extracts indicated a lower Vmax value in SHRSP (SHRSP, 0.47; WKY, 2.05 nmol/min/mg), and an unchanged Km value (SHRSP, 18.2; WKY, 19.6 microM). The activity of mevalonate-PP decarboxylase was also found to be reduced in other tissues, including the brain, testis, small intestine, and cultured vascular smooth muscle cells. From the above observations, we concluded that the lower activity of mevalonate-PP decarboxylase was responsible for the reduced cholesterol biosynthesis in the liver of SHRSP. |
| Liver mitochondrial P450 involved in cholesterol catabolism and vitamin D activation Okuda, K. I. (1994), J Lipid Res 35(3): 361-72. Abstract: The isolation, purification, and cloning of the mitochondrial P450 enzyme catalyzing not only the 27-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha-diol and cholestane-3 alpha, 7 alpha, 12 alpha-triol, but also the 25-hydroxylation of vitamin D3 are reviewed. The sterol hydroxylase was shown to be present on the mitochondrial inner membrane-matrix, to be inactivated by carbon monoxide, and to be activated by 450 nm radiation, establishing its membership in the P450 class. Characterization of the reaction product indicated that hydroxylation occurred on the 27 methyl group; the enzyme also mediated 25-hydroxylation of vitamin D3. Cloning of the enzyme confirmed that it was of mitochondrial origin and that it catalyzed both sterol and vitamin D hydroxylation. Enzymatic activity was deficient in fibroblasts from patients with cerebrotendinous xanthomatosis. Genetic analysis of patients with cerebrotendinous xanthomatosis has shown several genetic defects: 1) two different point mutations in which arginine codons were replaced by cysteine codons; 2) deletion of thymidine in exon 4; and 3) a guanosine to adenosine substitution at the 3' splice acceptor site of intron 4 of the gene. The mitochondrial 27-hydroxylase is a key enzyme in bile acid biosynthesis and can be distinguished from microsomal hydroxylases that also catalyze hydroxylation of the side chain of cholesterol and intermediates in bile acid biosynthesis. In the rat, a microsomal enzyme catalyzes 26-hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol, but the importance of this pathway in bile acid biosynthesis is unclear. |