Tryptophan receptor

Leucine is an essential, branched-chain amino acid that does not compete with tryptophan for nuclear tryptophan receptor binding in vitro.196 However, the addition of L-leucine to unlabeled L-tryptophan caused significantly less inhibition of 3H-tryptophan binding in vitro to hepatic nuclei than did unlabeled L-tryptophan alone.186 Also, L-isoleucine and L-valine revealed binding effects similar to that with L-leucine. In regard to hepatic protein synthesis, L-leucine alone has no effect, yet when added with L-tryp-tophan, it inhibits the increase of protein synthesis due to L-tryptophan alone. The mechanisms by which L-leucine acts are not yet clear. It does not appear to be related to altered transport of L-tryptophan, as can occur with branched-chain amino acids. Although L-leucine does not stimulate hepatic protein synthesis, it has been reported to stimulate muscle protein synthesis.188 Whether this effect of L-leucine on muscle may influence the liver response is not clear. 

Kurl, R. N., Barsoum, A. L., and Sidransky, H., Association of poly(A)poly-merase with tryptophan receptor in rat hepatic nuclei, ]. Nutr. Biochem., 3, 366, 1992. 

Hormones and Hepatic Nuclear Tryptophan Receptor Binding... 

The possible relationship between tryptophan and sodium ions has been considered in a number of studies. Herken and Weber165 reported that under certain conditions tryptophan injections intraperitoneally to rats led to a reduction of elimination of Na++. Subsequently, Reuter et al.166 analyzed the alterations of water and electrolyte balances by the use of clearance experiments. The fractional Na++ reabsorption increases, with no increase in the absolute tubular sodium transport rate since the significant reduced plasma-sodium concentration led to a decreased sodium load. The most probable cause of the decreased plasma-sodium concentrations seemed to be retention of sodium-free water under the conditions of infusion. The water retention is compatible with the antidiuretic effect of serotonin. Another relationship between tryptophan and sodium has been reported on the effects of each agent alone or together in vivo or in vitro, on in vitro hepatic nuclear tryptophan receptor binding and hepatic protein synthesis.167 168 This has been considered in detail in Chapter 4. 

Neurotoxins present in sea snake venoms are summarized. All sea snake venoms are extremely toxic, with low LD5Q values. Most sea snake neurotoxins consist of only 60-62 amino acid residues with 4 disulOde bonds, while some consist of 70 amino acids with 5 disulfide bonds. The origin of toxicity is due to the attachment of 2 neurotoxin molecules to 2 a subunits of an acetylcholine receptor that is composed of a2 6 subunits. The complete structure of several of the sea snake neurotoxins have been worked out. Through chemical modification studies the invariant tryptophan and tyrosine residues of post-synaptic neurotoxins were shown to be of a critical nature to the toxicity function of the molecule. Lysine and arginine are also believed to be important. Other marine vertebrate venoms are not well known. 

The apparent reliance of enzyme activation on phosphorylation and intracellular Ca + gives a clue as to how the rate of 5-HT synthesis might be coupled to its impulse-evoked release. Certainly, the impulse-induced increase in intracellular Ca +, and/or activation of the G protein-coupled receptors that govern synthesis of cAMP, could modify the activity of tryptophan hydroxylase. Indeed, this could explain why activation of either somal 5-HTia autoreceptors in the Raphe nuclei (which depress the firing rate of 5-HT neurons) or terminal 5-HTib autoreceptors (which depress 5-HT release) can reduce the production of cAMP and attenuate 5-HT synthesis. 

Biogenic amines are decarboxylated derivatives of tyrosine and tryptophan that are found in animals from simple invertebrates to mammals. These compounds are found in neural tissue, where they function as neurotransmitters, and in non-neural tissues, where they have a variety of functions. The enzymes involved in biogenic amine synthesis and many receptors for these compounds have been isolated from both invertebrate and vertebrate sources. In all cases, the individual proteins that effect biogenic amine metabolism and function show striking similarity between species, indicating that these are ancient and well-conserved pathways. 

TABLE 23-3 Examples of proteins regulated by phosphorylation Enzymes involved in neurotransmitter biosynthesis Tyrosine hydroxylase Tryptophan hydroxylase Neurotransmitter receptors Adrenergic receptors Dopamine receptors Opioid receptors Glutamate receptors Many others... 

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