LIPID METABOLISM 



'79 



V, A T/ 



FFA 

 CHYLOMICRONS 

 CARBOHYORATE 



fig. 5. Origins of serum lipids. 

 [From Van Itallie & Felch (201).] 



major organ of catabolism and excretion. Elaborate 

 mechanisms exist in the liver for disposal of the 

 steroid nucleus of cholesterol, since the body lacks 

 the mechanisms capable of opening the rings of 

 phenanthrene-like structure. 



Cholesterol Disposal 



As mentioned above, cholesterol represents a spe- 

 cial disposal problem. Fatty acids and glycerol are 

 readily metabolized, and phospholipids are freely 

 miscible with water and can be degraded rapidly. On 

 the other hand, although the isopropyl side chain of 

 the cholesterol molecule can be oxidized, with forma- 

 tion of bile acids and certain hormones, the steroid 

 nucleus itself is not degraded. 



It is now established that bile acids constitute the 

 major catabolic end products of cholesterol metabo- 

 lism in man and in a variety of animal species (17, 18, 

 97). In man, conversion of cholesterol to bile acids oc- 

 curs in the liver. The biochemical details of this con- 

 version have not been completely worked out. It is 

 generally agreed that in man two '"primary" bile 

 acids (hydroxycholanic acids) result from catabolism 

 of cholesterol in the liver: cholic acid and chenodeoxy- 

 cholic acid (fig. 6). Five important biochemical 

 changes must occur in the cholesterol molecule, and 

 not necessarily in the order listed : a) isomerization of 

 the 3 /J-OH into 3 a-OH; b) saturation of the 5:6 



double bond; c) hydroxylation at the 7 position 

 (chenodeoxycholic) d) hydroxylation at both 7 and 

 1 2 positions (cholic) ; and e) oxidation of the terminal 

 isopropyl group resulting in a C-24 acid (cholanic). 

 The resultant bile acids are secreted into the extra- 

 hepatic biliary system as micellar conjugated com- 

 pounds with either glycine or taurine. In man the con- 

 jugation process favors glycine by a factor of three 

 (18). In the intestine the bile acids may undergo fur- 

 ther chemical transformations attributed to intestinal 

 microorganisms, giving rise to "secondary" bile acids. 

 For example, cholic acid will lose its 7 a-OH group to 

 yield deoxycholic (3a, i2a-hydroxycholanic) acid, and 

 in a similar manner chenodeoxycholic acid will yield 

 lithocholic (3 a-hydrOxycholanic) acid. Thus the 

 7 a-dehydroxylation is a bacterial function. A number 

 of additional bacterial metabolites of hepatic bile acids 

 have been found in human feces, although their impor- 

 tance quantitatively has not been determined (in). 

 In addition, the bacteria split the conjugated com- 

 pounds into glycine, taurine and their corresponding 

 bile acids. Most of the bile acids are reabsorbed from 

 the intestine into the liver via the portal vein. A small 

 portion is excreted in the stool in unconjugated form. 

 In the normal gastrointestinal tract virtually no 

 cholic acid can be identified in the feces. 



It has been estimated that the normal adult indi- 

 vidual synthesizes about 1.2 g of cholesterol per day. 

 Approximately 70 per cent of this amount (0.8 g) is 



