Thyroid peroxidases

Vanadium. Vanadium is essential in rats and chicks (85,156). Estimated human intake is less than 4 mg/d. In animals, deficiency results in impaired growth, reproduction, and Hpid metaboHsm (157), and altered thyroid peroxidase activities (112). The levels of coen2yme A and coen2yme Q q in rats are reduced and monoamine oxidase activity is increased when rats are given excess vanadium (157). Vanadium may play a role in the regulation of (NaK)—ATPase, phosphoryl transferases, adenylate cyclase, and protein kinases (112). 

Thiocyanate ion, SCN , inhibits formation of thyroid hormones by inhibiting the iodination of tyrosine residues in thyroglobufin by thyroid peroxidase. This ion is also responsible for the goitrogenic effect of cassava (manioc, tapioca). Cyanide, CN , is liberated by hydrolysis from the cyanogenic glucoside finamarin it contains, which in turn is biodetoxified to SCN. 

Aromatic Amines and Phenols. The discovery that sulfaguanidine [57-67-0] was goitrogenic to rats was serendipitous. Many related compounds were then examined, and the aniline moiety was usually present (2,6). Such compounds, as well as resorcinol-like phenols, may act as goitrogens by inhibiting thyroid peroxidases. These are not used clinically. 

Propylthiouracil (PTU), but not methyl-mercaptoi-midazole (MMI), has an additional peripheral effect. It inhibits the monodeiodination of thyroxine to triiodothyronine by blocking the enzyme 5 mono-deiodinase [1]. In humans the potency of MMI is at least 10 times higher than that of PTU, whereas in rats PTU is more potent than MMI. The higher potency of MMI in humans is probably due to differences in uptake into the thyroid gland and subsequent metabolism, because in vitro inhibition of thyroid peroxidase by MMI is not significantly more potent than by PTU [1, 6]. Whether antithyroid drags have additional immunosuppressive actions is a matter of discussion [1, 2]. 

DIVI R L, DOERGE D R (1996) Inhibition of thyroid peroxidase by dietary flavonoids. Chem Res Toxicol. 9 16-23. 

Isoflavones have been implicated in goiter induction. Soybean extracts inhibit reactions catalyzed by thyroid peroxidase (TPO), essential to the synthesis of thyroid hormones (Divi et al., 1997). Genistein and daidzein (at about 1-10 p,M of IC50) may act as alternative substrates for tyrosine iodination (Divi et al., 1997). Furthermore, genistein and daidzein have also been shown to cause the irreversible inactivation of TPO in the presence of hydrogen peroxide. Genistein also inhibits thyroxine synthesis in the presence of iodinated... 

Thyroid peroxidase An enzyme that catalyzes the organification and coupling steps of thyroid hormone synthesis. 

Several compounds can be oxidized by peroxidases by a free radical mechanism. Among various substrates of peroxidases, L-tyrosine attracts a great interest as an important phenolic compound containing at 100 200 pmol 1 1 in plasma and cells, which can be involved in lipid and protein oxidation. In 1980, Ralston and Dunford [187] have shown that HRP Compound II oxidizes L-tyrosine and 3,5-diiodo-L-tyrosine with pH-dependent reaction rates. Ohtaki et al. [188] measured the rate constants for the reactions of hog thyroid peroxidase Compounds I and II with L-tyrosine (Table 22.1) and showed that Compound I was reduced directly to ferric enzyme. Thus, in this case the reaction of Compound I with L-tyrosine proceeds by two-electron mechanism. In subsequent work these authors have shown [189] that at physiological pH TPO catalyzed the two-electron oxidation not only L-tyrosine but also D-tyrosine, A -acetyltyrosinamide, and monoiodotyrosine, whereas diiodotyrosine was oxidized by a one-electron mechanism. 

The answer is c. (Katzung, pp 651-652.) Propylthiouracil is a thioamide that interferes with the production of thyroid hormone. Its primary action is prevention of thyroid hormone synthesis by blocking thyroid peroxidase catalysis leading to interference with iodine organification. 

The concentration of Li+ in the thyroid is three to four times that in serum [179]. It is thought that Li+ may be concentrated in the thyroid gland by a mechanism similar to the incorporation of iodide, I-, resulting in competition between Li+ and I the levels of intracellular 1 decrease when those of Li+ increase, and vice versa [182]. Li+ inhibits both the ability of the gland to accumulate 1 and the release of iodine from the gland. In vitro, Li+ has no effect on thyroid peroxidase, the enzyme that catalyzes the incorporation of I" into tyrosyl residues leading to thyroidal hormone synthesis, but does increase the activity of iodotyrosine-deio-dinase, which catalyzes the reductive deiodination of iodotyrosyls, thus maintaining the levels of intracellular I [182]. The increase in iodoty-rosine-deiodinase activity is probably a response to the Li+-induced decrease in the concentration of thyroidal I". Li+ has no effect on the conversion of thyroxine to triiodothyronine. The overall effect of this competition between Li+ and 1 is, therefore, reduced levels of thyroid hormone in the presence of Li+. 

The thyroid hormones thyroxine (T4) and triiodothyronine (T3) are formed on thyroglobulin, a large glycoprotein synthesized within the thyroid cell. Inorganic iodide enters the thyroid follicular cell and is oxidized by thyroid peroxidase and covalently bound (organified) to tyrosine residues of thyroglobulin. 

The iodinated tyrosine residues monoiodotyrosine (MIT) and diiodoty-rosine (DIT) combine (couple) to form iodothyronines in reactions catalyzed by thyroid peroxidase. Thus, two molecules of DIT combine to form T4, and MIT and DIT join to form T3. 

Thyroiditis/hypothyroidism 4600 83 % 17 alpha-hydroxylase, thyroid peroxidase Iodine... 

Taurog A, Dorris ML, Doerge DR. Minocycline and the thyroid antithyroid effects of the drug, and the role of thyroid peroxidase in minocycline-induced black pigmentation of the gland. 

Thyroxine synthesis begins when iodide (I-) is transferred from the blood stream to the thyroid follicle cell by an active ATP-driven membrane pump mechanism this process is stimulated by cAMP following TSH stimulation of the gland. Iodide is transported through the follicular cell and secreted into the lumen of the follicle where it is oxidized to iodine and incorporated in to tyrosine residues by the enzyme thyroid peroxidase (TPO). 

Thyroid peroxidase (TPO) oxidises iodide and incorporates iodine into tyrosine residues within Tgb. 

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