defective feedback inhibition of bile acid biosynthesis

It may be concluded that deoxycholic acid and possibly other secondary bile acids are much ..

Peroxisomes and bile acid biosynthesis - ResearchGate

If evidence can be supplied to show that an ester is readily hydrolysed in the body to constituents whose metabolic fate and biological actions are fully understood, further toxicological studies may not be necessary. Consequently, artificial gastro-intestinal juices have been used to study the hydrolysis of esters (Longland et al., 1977). Before absorption in vivo, the esters and acetals in this group can be reasonably predicted to undergo hydrolysis (Williams, 1959) to yield phenethyl alcohol, phenoxyethyl alcohol, phenylacetaldehyde, phenylacetic acid and phenoxyacetic acid. Phenethyl acetate (No. 989), methyl phenylacetate (No. 1008), ethyl phenylacetate (No. 1009), isopropyl phenylacetate (No. 1011), isoamyl phenylacetate (No. 1014) and citronellyl phenylacetate (No. 1021) were rapidly hydrolysed in vitroin simulated gastric juice and pancreatic juice (Nos 989, 1008 and 1009) (Longland et al., 1977) or in a buffered solution of pancreatin (Nos 1008, 1011, 1014 and 1021) (Grundschober, 1977) to the corresponding phenethyl derivatives. Phenethyl acetate (No. 989), ethyl phenylacetate (No. 1009) and isoamyl phenylacetate (No. 1014) were not hydrolysed by partially purified human plasma arylesterase (Augustinsson & Ekedahl, 1962).

30/11/2017 · Peroxisomes and bile acid biosynthesis

In animal models, this led to asignificant reduction of blood and body cholesterol and an increase in fecalsterol output, mostly neutral sterols.

A documented review on bile acids,present in all vertebrates except fish and bile alcohol present in fish, may beconsulted ().

Bile acids determination : As early as 1974, an almost completeseparation of bile acids was done by TLC ().

Several works provide evidencesof bile acid signaling in regulation of glucose and lipid metabolism ().

Several 3-keto-cholestenoic acids (dafachronic acids) were shown to be involvedin the control of dauer formation and reproduction in the nematode ().

Regulation of bile acid biosynthesis by hepatocyte ..

Within the intestines the primary bile acids areconverted by bacteria into the secondary bile acids, identified as deoxycholate (from cholate) and lithocholate (fromchenodeoxycholate).

Bile acid synthesis. Bile acids are synthesized from | …

Phenoxyacetic acid was fed to male rabbits at a dose of 100–200 mg/kg bw, and some animals also received glycine in amounts corresponding to three equivalents of the acid. In this test, 44–72% of the phenoxyacetic acid was recovered unchanged in the urine within 6 h and 82–105% within 24 h. There was no evidence of conjugation with either glucuronic acid or glycine, even when the diet was supplemented with glycine. A rabbit that received an oral dose of 500 mg of the glycine conjugate of phenoxyacetic acid excreted 30% of the dose unconjugated in the urine after 18 h (Levey & Lewis, 1947). In another study, 55% of an oral dose of an unspecified amount of phenoxyacetic acid was recovered in the urine of dogs and 61% in the urine of humans. No evidence for glycine or glucuronic acid conjugation was found (Thierfelder & Schempp, 1917).

Bile Acid Synthesis, Metabolism and Biological Functions

The effect of various primary and secondary bile acids on the rates of synthesis of all major bile acids was studied in the live rat with an extracorporal bile duct. Bile acid synthesis was determined using HPLC based on mass or by isotope dilution. Derepressed rates of bile acid synthesis (30-54 h) were inhibited by an infusion of taurocholic acid only at a supraphysiological dose of 500 mumol/kg per h, but not at 300 mumol/kg per h, which approximates the initial bile acid secretion (250 mumol/kg per h). When administered together with taurocholic acid (200 mumol/kg per h) only a high dose of taurochenodeoxycholic acid (100 mumol/kg per h) decreased taurocholic but not tauromuricholic or taurochenodeoxycholic acid synthesis. The only bile acid suppressing taurocholic acid (36-71%) and taurochenodeoxycholic acid (up to 33%) formation at an infusion rate close to the normal portal flux was deoxy- or taurodeoxycholic acid at 15-50 mumol/kg per h. It may be concluded that deoxycholic acid and possibly other secondary bile acids are much more potent inhibitors than primary bile acids.

Bile Acid Synthesis and Utilization

Phenethyl alcohol is successively oxidized to phenylacetaldehyde and phenylacetic acid in vivo Phenylacetic acid undergoes species-specific conjugation with a variety of amino acids, amines or glucuronic acid, followed by excretion almost exclusively in the urine (James et al., 1972; see Figure 2). Phenethyl alcohol is readily oxidized to phenylacetaldehyde by an assortment of NAD+-dependent alcohol and aldehyde dehydrogenases (Bosron & Li, 1980). The greatest activity of mammalian alcohol dehydrogenases (ALDH) occurs in the liver, where they show broad substrate specificity for the oxidation of primary aliphatic and aromatic alcohols. Human liver ALDH showed a decreased Michaelis-Menten constant (Km, the concentration of the specific substrate at which a given enzyme yields one-half its maximum velocity with increasing lipophilicity); however, the maximum rate or velocity of an enzymatic reaction which is indicative of all the enzyme active site(s) complexed with substrate, Vmax, remained essentially constant, suggesting that the rate-limiting step does not involve the binding or release of the alcohol or aldehyde intermediate (Pietruszko et al., 1973).