Bile acids, physiological functions

Many important biomolecules are derived from amino acids. Glycine is a precursor of porphyrins. Degradation of iron-porphyrin (heme) generates bilirubin, which is converted to bile pigments, with several physiological functions. 

Structure-Activity Reiationships for ASBT. The studies with endogenous bile acids have led to physiological understanding of the function of bile acids and the enterohepatic circulation. The search for a deeper understanding of the molecular mechanism behind the affinity and recognition of molecules by the bile acids carriers in both ileum and liver has led researchers to modify bile acids and study the carrier affinity of these compounds. These modifications typically entail either the substitution of the hydroxyl groups at the 3,7, or 12 positions by other functionalities or the... 

After cholesterol is formed, it can be converted to other steroids of widely varying physiological function. The smooth ER is an important site for both the synthesis of cholesterol and its conversion to other steroids. Most of the cholesterol formed in the liver, which is the principal site of cholesterol synthesis in mammals, is converted to bile acids, such as cholate and glycocholate (Figure 21.30). These compounds aid in the digestion of lipid droplets by emulsifying them and rendering them more accessible to enzymatic attack. 

Some T. have major physiological significance. Thus, lanosterol is converted biosynthetically to cholesterol, the precursor of all steroid hormones, bile acids, and vitamin D3. In fungi, lanosterol is converted to er-gosterol (see sterols), an essential component of the fungal cell membrane. Plant cell membranes also incorporate steroids (phytosterols). In prokaryotes, the hopanoids take over the functions of steroids in the cell membranes. As a component of animal and plant waxes T. strengthen the structures. They protect the plant surface from desiccation and attack by microorganisms (e.g., betulin, lupeol, oleanolic acid, and ursolic acid). 

Publication of a book devoted entirely to the chemistry, physiology, and metabolism of bile acids indicates a renascence in interest in these poly-functional detergents. Here we will summarize present views on the physical and physiological properties of bile acids in relation to their chemical structure which bear on their participation in the intestinal absorption of fat, their enterohepatic circulation, and their influence on electrolyte and water absorption by the colon. Several of these topics are considered in detail elsewhere in this book, as well as in recent reviews (1-4). This chapter will focus on our own studies but will also emphasize areas in which information is needed. 

Clearance tests of liver function assess a number of physiologic activities including hepatic uptake, hepatic metabolism, and hepatic excretion. Typical clearance tests of liver function include indocyanine green (ICG), antipyrine clearance test and C aminopyrine breath test. These tests give an estimation of the ability of the liver to extract and detoxify exogenous toxins (xenobiotics). Measuring the excretion of endogenously produced serum bile acids is an additional measure of hepatic clearance and has been used as a sensitive measure of early solvent hepatotoxicity." "... 

The topic of bile acids has been the subject of a number of general reviews and books (28, 29, 30, 33, 34). Certain reviews have dealt, in part, with physicochemical aspects of the bile salts (35-39) or have mentioned physicochemical properties only briefly (28, 30, 34, 40). A review dealing specifically with the physicochemical properties of bile salts and their relation to physiologic function was published in 1967 (1). This chapter will be limited to a discussion of the physicochemical properties of bile acids and their salts. (For physiologic correlations, see 1, 8, 9, 10, 41, and 197.)... 

A major and striking physicochemical difference between lithocholic acid and the dihydroxy and trihydroxy bile acids is the insolubility of the sodium salts of the former (10, 45). Sodium salts of the common bile acids (taurine and glycine conjugates of cholic acid, deoxycholic acid, and che-nodeoxycholic acid) are very soluble in water and physiological saline, even at 0°C. The solubility of the ammonium, lithium, sodium, potassium, rubidium, and cesium salts of lithocholic acid (NH4L, LiL, NaL, RbL, CsL) have been studied in water as a function of temperature (45). 

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