Bile acids, steroids from

Bile acids, steroids from, 188 Biperidin, 47 Birch, Arthur J., 163 Birch reduction, 163, 167, 170 Bishydroxycoumarin, 331 Bismethylenedioxy group, 193 Blocking agents, of B-sympathet-ic receptors, 65, 117... 

The C>4 bile acids arise from cholesterol in the liver after saturation of the steroid nucleus and reduction in length of the side chain to a 5-carbon add they may differ in the number of hydroxyl groups on the sterol nucleus. The four acids isolated from human bile include cholic acid (3,7,12-tiihydroxy), as shown in Fig. 1 deoxycholic acid (2,12-dihydroxy) chenodeoxycholic acid (3,7-dihydroxy) and lithocholic acid (3-hydroxy). The bile acids are not excreted into the bile as such, but are conjugated through the C24 carboxylic add with glycine or... 

Glucuronidation is an important step in the elimination of many important endogenous substances from the body, including bilirubin, bile acids, steroid hormones, thyroid hormones, retinoic acids, and biogenic amines such as serotonin. Many of these compounds are also substrates for sulfonyltransferases (SULTs) (2). 

See also Steroids, Molecular Structures and Properties of Lipids (from Chapter 10), Bile Acids, Steroid Hormone Synthesis... 

A series of non-polar cation exchangers based upon Sephadex LH-20 or Lipidex-1000 is claimed to have useful characteristics for the isolation of steroids from biological fluids prior to g.c.-m.s. analysis.A rapid and inexpensive enzymic method for analysis of bile-acid mixtures from natural sources is claimed to give results similar to those obtained by chromatographic procedures. 

Bile acids differ from most other steroids in that they have a cis configuration at the junction of rings A and B. 

The elucidation of the structure of bile acids stems from the early observations of Adolf Windaus and of Heinrich Wieland that cholanic acid could be obtained from either cholesterol or cholic acid they inferred from this that bile acids are steroidal in nature. Wieland and his group showed... 

Initial steroid research involved isolation of sterols and bile acids from natural sources. DeFourcroy is generally credited with the discovery of cholesterol [57-88-5] (2) in 1789 (3). In 1848, choHc acid [81-25-4] (3) was isolated from the saponification of ox bile and its elementary composition deterrnined as... 

With the shift of raw materials, first from cholesterol to bile acids, then to plant sapogenins such as diosgenin, 17- keto steroids were no longer directly available, and improved methods for the degradation of 20-ketopregnanes (which were the principal products from these new sources) had to be developed. 

Cholesterol, an amphipathic lipid, is an important component of membranes. It is the parent molecule from which all other steroids in the body, including major hormones such as the adrenocortical and sex hormones, D vitamins, and bile acids, are synthesized. 

Another example of a nudibranch, which probably modifies dietary metabolites to obtain more effective allomones, is seen in Aldisa cooperi (= A. sanguinea cooperi) [155]. It elaborates two fish antifeedant bile acids (104,105) that are absent in its prey, the sponge Anthoarcuata graceae, where the main steroid is 4-cholesten-3-one (106). Biosynthetic experiments starting from both labelled mevalonic acid and labelled 4-eholesten-3-one would definitely clarify, whether, the two allomones (104-105) are biosynthetized de novo by the mollusc, or if they are derived from a food source. 

Endogenous and exogenous androgens can be derivatized with trimethylsilyl (TMS) for hydroxy functions and by 0-methylation for ketones, and analyzed with GC-FID or GC-MS (Shimada et al., 2001). MS is more prevalent due to unequivocal identification and greatly increased sensitivity but FID is still used in laboratories for some steroids. Sterols have typically been analyzed by GC-FID and GC-MS with derivatization to optimize peak shape (Shimada et al., 2001), and bile acids can be derivatized with M-butyl ester-TMS ether and analyzed by GC-FID from plasma samples (Batta et al., 1998). Juricskay and Telegdy (2000) reported an assay capable of analyzing 28 steroids in urine samples using GC-FID. 

Although both LDL and HDL are primarily cholesterol particles, most of the cholesterol measured in the blood is assodated with LDL. The normal role of LDL is to deliver cholesterol to tissues for biosynthesis. When a cell is repairing membrane or dividing, the cholesterol is required for membrane synthesis. Bile acids and salts are made from cholesterol in the liver, and many other tissues require some cholesterol for steroid synthesis. As shown in Figure 1-15-6, about 80% of LDL are picked up by hepatocytes, the remainder by peripheral tissues. ApoB-100 is the only apoprotein on LDL, and endocytosis of LDL is mediated by apoB-100 receptors (LDL receptors) clustered in areas of cell membranes lined with the protdn clathrin. 

Cholesterol is required for membrane synthesis, steroid synthesis, and in the liver, bile acid synthesis. Most cells derive their cholesterol from LDL or HDL, but some cholesterol may be synthesized de novo. Most de novo synthesis occurs in the liver, vfhere cholesterol is synthesized from acetyl CoA in the cytoplasm. The citrate shutde carries mitochondrial acetyl CoA into the cytoplasm, and NADPH is provided by the HMP shunt and malic enzyme. Important points are noted in Figure 1-15-9,... 

A and B are in cis position relative to each other (see p. 54). One to three hydroxyl groups (in a position) are found in the steroid core at positions 3, 7, and 12. Bile acids keep bile cholesterol in a soluble state as micelles and promote the digestion of lipids in the intestine (see p.270). Cholic add and cheno-deoxychoMc acid are primary bile acids that are formed by the liver. Their dehydroxylation at C-7 by microorganisms from the intestinal flora gives rise to the secondary bile acids lithocholic acid and deoxycholic acid. 

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