Liver taurine synthesis

Taurine is a dietary essential in the cat, which is an obligate carnivore with a limited capacity for taurine synthesis from cysteine. On a taurine-free diet, neither supplementary methionine nor cysteine will maintain normal plasma concentrations of taurine, because cats have an alternative pathway of cysteine metabolism reaction with mevalonic acid to yield felinine (3-hydroxy-1,1-dimethylpropyl-cysteine), which is excreted in the urine. The activity of cysteine sulfinic acid decarboxylase in cat liver is very low. 

Administration of methoxamine, an a-agonist and vasoconstrictor, to rodents also produced a decrease in cardiac tissue and an increase in blood levels of taurine. On the other hand, taurine levels in the liver increased approximately 2.5- to 3-fold. While it is known that liver is capable of sequestering exogenous taurine, it can be calculated that the loss of taurine from the heart was quantitatively not sufficient to account for the increase in the liver. Thus the source of the increased taurine content of the liver is not known. Whether methoxamine stimulated de novo taurine synthesis in the liver or caused a loss of taurine from tissues other than the heart (such as skeletal muscle) which in turn was taken up by the liver requires further experimentation. 

Bile salts secreted into the intestine are efficiently reabsorbed (greater than 95 percent) and reused. The mixture of primary and secondary bile acids and bile salts is absorbed primarily in the ileum. They are actively transported from the intestinal mucosal cells into the portal blood, and are efficiently removed by the liver parenchymal cells. [Note Bile acids are hydrophobic and require a carrier in the portal blood. Albumin carries them in a noncovalent complex, just as it transports fatty acids in blood (see p. 179).] The liver converts both primary and secondary bile acids into bile salts by conjugation with glycine or taurine, and secretes them into the bile. The continuous process of secretion of bile salts into the bile, their passage through the duodenum where some are converted to bile acids, and their subsequent return to the liver as a mixture of bile acids and salts is termed the enterohepatic circulation (see Figure 18.11). Between 15 and 30 g of bile salts are secreted from the liver into the duodenum each day, yet only about 0.5 g is lost daily in the feces. Approximately 0.5 g per day is synthesized from cholesterol in the liver to replace the lost bile acids. Bile acid sequestrants, such as cholestyramine,2 bind bile acids in the gut, prevent their reabsorption, and so promote their excretion. They are used in the treatment of hypercholesterolemia because the removal of bile acids relieves the inhibition on bile acid synthesis in the liver, thereby diverting additional cholesterol into that pathway. [Note Dietary fiber also binds bile acids and increases their excretion.]... 

Bile salts (or bile acids) are polar derivatives of cholesterol and constitute the major pathway for the excretion of cholesterol in mammals. In the liver, cholesterol is converted into the activated intermediate cholyl CoA which then reacts either with the amino group of glycine to form glycocholate (Fig. 3a), or with the amino group of taurine (H2N-CH2-CH2-S03", a derivative of cysteine) to form taurocholate (Fig. 3b). After synthesis in the liver, the bile salts glycocholate and taurocholate are stored and concentrated in the gall bladder, before release into the small intestine. Since they contain both polar and nonpolar... 

Some pyridoxal phosphate-dependent enzymes are normally fuUy saturated with cofactor and show the same activity on assay in vitro whether additional pyridoxal phosphate is present in the incubation medium or not. Examples of this class of enzymes include liver cysteine sulfinate decarboxylase (which is involved in the synthesis of taurine from cysteine Section 14.5.1) and the brain and liver glutamate and aspartate aminotransferases. 

The mechanism of action of o-thyroxine appears to be stimulation of oxidative cataboli.sm of cholesterol in the liver through stimulation of 7-a-cholcstcrol hydroxylase, the rate-limiting enzyme in the conversion of cholesterol to bile acids. The bile acids arc conjugated with glycine or taurine and excreted by the biliary route into the feces. Although thyroxine docs not inhibit cholesterol bio.synthesis. it increases the number of LDL receptors, enhancing removal of LDL from plasma. 

Methionine produces cystine and taurine breaks down fats reduces blood cholesterol detoxifies the liver is an antioxidant and protects hair, skin, and nails. It is needed for synthesis of RNA and DNA and it assists in the breakdown of niacin, histamine, and adrenalin. It binds to heavy metals, such as lead and cadmium, and carries them out of the body. 

The demonstration by Bergstrom et al. (4,5) in 1953 of the conversion of deoxycholic acid to taurocholic acid in the rat in vivo and by rat liver slices paved the way for studies on 7a-hydroxylation and conjugation of bile acids. The early work on the synthesis of bile acid conjugates in vitro utilized slices or homogenates of rat and human liver, and the enzymatic reaction was followed by the incorporation of radioactivity from carboxyl- C-labeled bile acids into the corresponding taurine and glycine conjugates (6,7). The... 

Sarkar et confirmed the localization of the hippuric acid-synthesizing enzyme in the mitochondria of rat liver homogenate, found that the synthesis was abolished by dinitrophenol (see below for the significance of this finding), that benzoic acid can be replaced by some other aromatic and heterocyclic carboxylic acids (phenylacetic and cholic acids were inactive), and that glycine could not be replaced by either jS-alanine or taurine. 

In mammalian liver parenchyma cells, the synthesis of the steroid skeleton which was described on p. 236 is extended by acquisition of an enzyme system leading to the production of the substances known as bile acids. In man, this s3mthesis yields cholic acid, desoxycholic acid and chenodesoxycholic acid. The hepatic parenchyma in mammals also conjugates these bile acids with taurine and with glycine. 

Bile acids are formed from cholesterol in the liver via a sequence of reactions initiated by 7a-hydroxylase. Two primary bile acids, cholic acid and chenodeoxycholic acid, are formed and secreted as glycine or taurine conjugates into the bile and intestine. Most of them are reabsorbed, taken up by the liver and resecreted, completing enterohepatic circulation of bile salts. During each cycle a small amount of bile acids escape into the colon and feces and is regenerated by new hepatic synthesis. 

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