Catecholamines, hepatic metabolism

In the rat, the most often studied animal species, whose tryptophan metabolism resembles closely that of humans, acute ethanol administration, as described earlier, induces a biphasic effect on serum tryptophan levels, an initial increase followed by a later inhibition. Similarly, acute ethanol administration exerts a biphasic effect on brain serotonin synthesis and turnover, an initial enhancement followed by a later inhibition.111 The initial enhancement is caused by an increase in circulating free tryptophan availability to brain, probably secondary to a catecholamine-dependent lipolysis and a nonesteri-fied fatty acid-mediated displacement of the albumin-bound amino acid, whereas the later inhibition of serotonin synthesis and turnover is the result of a decrease in circulating free and albumin-bound tryptophan availability to the brain secondary to activation of hepatic tryptophan 2,3-dioxygenase (TP) by the earlier increase in free tryptophan to the liver. The activation of hepatic TP by acute ethanol administration, which is substrate (tryptophan) mediated, has been described in rats by Badawy and Evans.111127128... 

I. Mechanism of toxicity. Carbon tetrachloride and chloroform are CNS depressants and potent hepatic and renal toxins. They may also increase the sensitivity of the myocardium to arrhythmogenic effects of catecholamines. The mechanism of hepatic and renal toxicity is thought to be a result of a toxic free-radical intermediate of cytochrome P-450 metabolism. (Bioactivation of CCI4 has become a model for chemical toxicity induced by free radicals.) Chronic use of metabolic enzyme inducers such as phenobarbital and ethanol increases the toxicity of carbon tetrachloride. Carbon tetrachloride is a known animal and suspected human carcinogen. Chloroform is embryotoxic and an animal carcincogen. 

In the study presented in Reference 15, we focused our attention on spontaneous processes of chiral conversion and peptidization running in aqueous acetonitrile solution of L-Met (Scheme 19.3). We chose this amino acid due to its important functions in the human body. L-Met is a donor of methyl groups in the metabolic processes of methyl group transfer it plays an important role in synthesis of choline and lecithin, promotes normalization of lipid metabolism and hepatic steatosis, and has an anti-atherosclerotic activity. Furthermore, L-Met plays an important role in the activities of the adrenal gland, in particular in the synthesis of adrenaline, and in the processes of inactivation of catecholamines, thereby regulating the catecholamine balance. The existence of a close relationship has also been proven between L-Met, folate transformations, and vitamins B6 and B12 [25]. 

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