Iodide metabolism

Figure 42-11. Model of iodide metabolism in the thyroid follicle. A follicular cell is shown facing the follicular lumen (top) and the extracellular space (at bottom). Iodide enters the thyroid primarily through a transporter (bottom left). Thyroid hormone synthesis occurs in the follicular space through a series of reactions, many of which are peroxidase-mediated. Thyroid hormones, stored in the colloid in the follicular space, are released from thyroglobulin by hydrolysis inside the thyroid cell. (Tgb, thyroglobulin MIT, monoiodotyrosine DIT, diiodotyro-sine Tj, triiodothyronine T4, tetraiodothyronine.) Asterisks indicate steps or processes that are inherited enzyme deficiencies which cause congenital goiter and often result in hypothyroidism.

Iodide Metabolism Involves Several Discrete Steps... 

Bercz JP, Jones L, Harrington RM, et al. 1986. Mechanistic aspects of ingested chlorine dioxide on thyroid fonction impact of oxidants on iodide metabolism. Environ Health Perspect 69 249-255. 

In discussing iodide metabolism, we need only be concerned with the fate of inorganic iodides because organic iodides (tyrosine derivatives) are absorbed and enter the normal plasma pool of organic iodides produced by the thyroid. The site and the mechanism of absorption of organic iodides in the intestine are not exactly known, but somehow the dietary iodine is transported from the intestinal lumen into the blood. 

The concept of autoregulation of iodide metabolism was established several decades ago and autoregulation was originally defined as the regulation of thyroidal iodine metabolism independent from TSH or other externeil stimulators, and the major autoregulatory factor was considered to be excess iodide. 

Only the small amounts of T and T that are free in the circulation can be metabolized. The main route is deiodination of T to T and i-T, and from these to other inactive thyronines (21). Most of the Hberated iodide is reabsorbed in the kidney. Another route is the formation of glucuronide and sulfate conjugates at the 4 -OH in the Hver. These are then secreted in the bile and excreted in the feces as free phenols after hydrolysis in the lower gut. 

The most important pathway for the metabolism of T4 is monodeiodination. The removal of an iodide from the outer ring of T4 yields T3. Since the affinity of nuclear TRs is much higher for T3 than T4, outer ring monodeiodination of T4 to yield T3 produces a more active metabolite. Conversely, removal of an iodide from the inner ring of T4 yields an inactive metabolite, rTj. Both T3 and rT3 may undergo subsequent deiodinations to yield totally deiodinated thyronine (To). 

B. Selenium in the form of selenocysteine is required for three enzymes that remove iodide from thyroid hormones. There are no signihcant areas in which dietary intake of sodium or potassium are problems. Fluorine deficiency is not associated with thyroid hormone metabolism. 

Kaiser, S.C. Metabolism of 2-formy1-1-methyl pyridinium iodide... 

If caused by maternal TSH-R Ab [stim], the disease is usually self-limited and subsides over a period of 4-12 weeks, coinciding with the fall in the infant s TSH-R Ab [stim] level. However, treatment is necessary because of the severe metabolic stress the infant experiences. Therapy includes propylthiouracil in a dose of 5-10 mg/kg/d in divided doses at 8-hour intervals Lugol s solution (8 mg of iodide per drop), 1 drop every 8 hours and propranolol, 2 mg/kg/d in divided doses. Careful supportive therapy is essential. If the infant is very ill, oral prednisone, 2 mg/kg/d in divided doses, will help block conversion of T4 to T3. These medications are gradually reduced as the clinical picture improves and can be discontinued by... 

Hallier, E., Deutschmarm, S., Reichel, C., Bolt, H.M. Peter. H. (1990) A comparative investigation of the metabolism of methyl bromide and methyl iodide in human erythrocytes. Int. Arch, occup. environ. Health, 62, 221-225... 

Methyl iodide induces DNA damage and is mutagenic to bacteria in the presence or absence of an exogenous metabolic system. It induces mitotic recombination in yeast and mutations in cultured mammalian cells. It induces transformation in Syrian hamster embryo cells but not in C3H lOT A cells. 

In Chapter 9, the displacement of an iodide ion from methyl iodide by a hydroxide ion (Eq. 9-76) was considered. Can we similarly displace a methyl group from ethane, CH3-CH3, to break the C-C bond and form CH3OH The answer is no. Ethane is perfectly stable in sodium hydroxide and is not cleaved by a simple displacement process within our bodies. Likewise, long hydrocarbon chains such as those in the fatty acids cannot be broken by a corresponding process during metabolism of fatty acids. Not every structure will allow a nucleophilic displacement reaction to occur and not every anion or neutral base can act to displace another group. 

An important product of tyrosine metabolism in vetebrates is the thyroid hormone101 of which the principal and most active forms are thyroxine (T4) and triiodothyronine (T3).102 The thyroid gland is rich in iodide ion, which is actively concentrated from the plasma to 1 pM free I. 103 This iodide reacts under the influence of a peroxidase (see Fig. 16-14 and accompanying discussion)104 to iodinate tyrosyl residues of the very large 660-kDa dimeric thyroglobulin, which is stored in large amounts in the lumen of the... 

Chlorexolone as diuretic, 1, 174 Chlorides synthesis, 1, 448 Chlorin, 4, 370 metal chelates, 4, 391 Chlorin, dihydroxy-, 4, 393 Chlorin e6, 4, 404 trimethyl ester, 4, 398 synthesis, 4, 416 Chlorination pyridazines, 3, 20, 21 Chlorine trifluoride bonding, 1, 564 Chlorin-phlorin, 4, 398 Chlorins, 4, 378 absorption spectra, 4, 389 formation, 4, 394 molecular structure, 4, 385 oxidation, 4, 395 Chlorisondamine chloride as hypertensive agent, 1, 176 Chlormethiazoles metabolism, 1, 235 Chlormethiuron against ectoparasites veterinary use, 1, 217 Chlormezanone as antidepressant, 1, 169 Chlorocruoroheme, 4, 380 Chlorofucin conformation, 7, 703 Chloronium iodide, biphenylene-reactions, 1, 566... 

---