Amino acid thyroid-active

The in vitro effects of thyroid hormones on enzymes in some instances parallel the changes which have been noted in vivo, and in some instances do not. For example, an increased succinoxidase activity can be demonstrated both in vitro and in vivo under the influence of thyroxine. On the other hand, whereas D-amino acid oxidase activity is increased in thyrotoxicosis, thyroxine in vitro inhibits this enzyme. Some of these similarities and discrepancies will be pointed out in the subsequent sections. 

Nuclear hormone receptor (NHR) A transcription factor whose activity is regulated by a small molecule (the ligand), such as a steroid (estrogen, cortisol, etc.) or an amino acid (thyroid hormone). Most NHRs are transcriptional activators in the presence of ligand some NHRs also act as transcriptional repressors in its absence. 

Amino acid-derived hormones include the catecholamines, epinephrine and norepinephrine (qv), and the thyroid hormones, thyroxine and triiodothyronine (see Thyroid AND ANTITHYROID PREPARATIONS). Catecholamines are synthesized from the amino acid tyrosine by a series of enzymatic reactions that include hydroxylations, decarboxylations, and methylations. Thyroid hormones also are derived from tyrosine iodination of the tyrosine residues on a large protein backbone results in the production of active hormone. 

The term chiral recognition refers to a process in which some chiral receptor or reagent interacts selectively with one of the enantiomers of a chiral molecule. Very high levels of chiral recognition are cormnon in biological processes. (—)-Nicotine, for example, is much more toxic than (-F)-nicotine, and (-F)-adrenaline is more active than (—)-adrenaline in constricting blood vessels. (—)-Thyroxine, an amino acid of the thyroid gland that speeds up metabolism, is one of the most widely used of all prescription... 

A several-week supply of T3 and T4 exists in the thy-roglobidin that is stored in colloid in the lumen of the thyroid foUicles. These hormones can be released upon stimulation by TSH. This is the most exaggerated example of a prohormone, as a molecule containing approximately 5000 amino acids must be first synthesized, then degraded, to supply a few molecules of the active hormones T4 and T3. 

Derived from the amino acid tyrosine, thyroid hormones are unique because they contain iodine. At this time, its incorporation into thyroid hormones is the only known use for iodine in the body. There are two thyroid hormones, named for the number of iodides added to the tyrosine residues of the thyroglobulin triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine). Although significantly more T4 is synthesized by the thyroid gland, T3 is the active hormone. At the target tissue, T4 is deiodoninated to form the more potent T3. 

Hormonal actions on target neurons are classified in terms of cellular mechanisms of action. Hormones act either via cell-surface or intracellular receptors. Peptide hormones and amino-acid derivatives, such as epinephrine, act on cell-surface receptors that do such things as open ion-channels, cause rapid electrical responses and facilitate exocytosis of hormones or neurotransmitters. Alternatively, they activate second-messenger systems at the cell membrane, such as those involving cAMP, Ca2+/ calmodulin or phosphoinositides (see Chs 20 and 24), which leads to phosphorylation of proteins inside various parts of the target cell (Fig. 52-2A). Steroid hormones and thyroid hormone, on the other hand, act on intracellular receptors in cell nuclei to regulate gene expression and protein synthesis (Fig. 52-2B). Steroid hormones can also affect cell-surface events via receptors at or near the cell surface. 

The transport of amino acids at the BBB differs depending on their chemical class and the dual function of some amino acids as nutrients and neurotransmitters. Essential large neutral amino acids are shuttled into the brain by facilitated transport via the large neutral amino acid transporter (LAT) system [29] and display rapid equilibration between plasma and brain concentrations on a minute time scale. The LAT-system at the BBB shows a much lower Km for its substrates compared to the analogous L-system of peripheral tissues and its mRNA is highly expressed in brain endothelial cells (100-fold abundance compared to other tissues). Cationic amino acids are taken up into the brain by a different facilitative transporter, designated as the y system, which is present on the luminal and abluminal endothelial membrane. In contrast, active Na -dependent transporters for small neutral amino acids (A-system ASC-system) and cationic amino acids (B° system), appear to be confined to the abluminal surface and may be involved in removal of amino acids from brain extracellular fluid [30]. Carrier-mediated BBB transport includes monocarboxylic acids (pyruvate), amines (choline), nucleosides (adenosine), purine bases (adenine), panthotenate, thiamine, and thyroid hormones (T3), with a representative substrate given in parentheses [31]. 

The thyroid hormone thyroxine (tetraiodo-thyronine, T4) and its active form triiodothyronine (T3) are derived from the amino acid tyrosine. The iodine atoms at positions 3 and 5 of the two phenol rings are characteristic of them. Post-translational synthesis of thyroxine takes place in the thyroid gland from tyrosine residues of the protein thyro-globulin, from which it is proteolytically cleaved before being released, iodothyronines are the only organic molecules in the animal organism that contain iodine. They increase the basal metabolic rate, partly by regulating mitochondrial ATP synthesis, in addition, they promote embryonic development. 

The ratio of oxygen uptake to ammonia excretion in Black Sea mussels has been found to exhibit a distinct daily rhythm (Slatina, 1986). As a rule, the ammonia coefficient (O/N) tends to increase greatly at night. As this rise in energy metabolism does not result from an enhanced locomotor activity, it is difficult to explain or to find any analogue in fish. Farbridge and Leatherland (1987) demonstrated a strong effect of the lunar cycles on amino acid uptake by the scales, also on nucleic acids, metabolic reserves and plasma thyroid hormones in coho salmon. 

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