Liver enterohepatic cycle

Although in principle the metabolic clearance of plasma T3 may occur via several pathways, direct deiodination of the inner ring of T3 by the type I enzyme seems of minor importance (Section 2.2). Also, glucuronidation in the liver does not represent an irreversible pathway of T3 elimination since enzymatic hydrolysis of the conjugate in the intestine allows for the reabsorption of free T3 (enterohepatic cycle). Further, the finding that plasma T3 clearance is not affected in patients with liver cirrhosis [115] suggests that hepatic metabolism of T3 by sulfation and subsequent deiodination is less important than in rats. It appears, therefore, that the type III deiodinase of extrahepatic tissues is a major site for the clearance of plasma T3 as it is also for the production of plasma rT3. 

The silymarin complex is aptly suited for its hepatuprotec-tivc actions. Silymarin undergoes enterohepatic cycling, moving from intestine to liver and concentrating in liver cells. Protein. synthesis is induced in the liver by. silybin. 

Medications metabolized by the liver are secreted into bile. Bile enters the intestine and is eliminated in feces. Fat-soluble medications are reabsorbed from bile into the bloodstream and returned to the liver to be metabolized and eliminated by the kidneys. This process is called the enterohepatic cycle. Medications that are not metabolized by the liver are eliminated by the lungs at a rate that corresponds to the patient s respiration rate. These are volatile medications, such as anesthetics and medications that are metabolized to C02 and H20. Side effects such as rashes and skin reaction are commonly seen at sweat and salivary glands. For example, a patient may report tasting the medication. Medication excreted into saliva is eventually swallowed, reabsorbed, and... 

Figure 35.11 Enterohepatic cycling. Some drugs can move from the blood circulation to the liver, into the bile, into the intestine, to the liver, and back into circulation. This cycling decreases the rate of drug excretion.

It was suggested by Hillman (H6) that an enterohepatic cycle has an important role in folate homeostasis. This was based on the observation that alcohol appeared to reduce the level of folate supplied to serum and tissue by interfering with folate clearance into bile. Studies in rats of this aspect of the folate cycle confirm that the enterohepatic pathway has a major role in folate homeostasis. It has been shown that when small amounts of radio-labeled methylpteroylmonoglutamate and pteroylmonoglutamate are placed in the rat jejunum they are both rapidly absorbed and transported to the liver. They are then cleared into the bile predominantly in the methyl form. The original methyl form appears in the bile unchanged 10 min after administration and the pteroylmonoglutamate appears in the bile after conversion to the methyl form in a similar time period. This confirms that only a very short period of time is required for methylation. Bile folate is reabsorbed for... 

The final ratio between cholic acid and chenodeoxycholic acid in bile is influenced also by factors other than the activity of the hepatic 12a-hydroxylase. Thus, the differential rates of enterohepatic cycling, intestinal absorption and degradation are of importance. Ahlberg et al. did not find a correlation between microsomal 12a-hydroxylase activity and the ratio between cholic acid and chenodeoxycholic acid in the bile of some normo- and hyperlipidaemic patients [253]. In a recent in vivo study, Bjorkhem et al. failed to show a correlation between the apparent 12a-hydroxylase activity and the ratio between biliary cholic and chenodeoxycholic acid in healthy subjects and a patient with liver cirrhosis [254]. In this study, a mixture of [ H]7a,12a-dihydroxy-4-cholesten-3-one and [ C]7a-hydroxy-4-choles-ten-3-one was administered intravenously and the relative 12a-hydroxylase activity was calculated from the ratio between and in cholic acid. 

Dmgs that are metabolized by the liver are secreted into bile and then passed through the intestines and eliminated in feces. During this process, the bloodstream might reabsorb fat-soluble drags and return them to the liver where they are metabolized and eliminated by the kidneys. This is called the enterohepatic cycle. 

This conclusion must be considered tentative at present. The half-life of a bile acid refers to the interval from secretion by the liver to excretion in the feces. It cannot take into account the number of enterohepatic cycles undergone by a bile acid molecule before it is excreted. Presumably, it is the rate of the enterohepatic circulation of bile acids that controls the rate of bile acid biosynthesis (28), and we do not know at present what factor or factors determine the rate of excretion. In the experiments in which the enterohepatic circulation was interrupted by administering the ion exchanger, it may be postulated that synthesis was stimulated by partial removal of the bile acid pool the mechanism of this effect is not unequivocal since the circulation rate of the pool was not known. 

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