plant toxin 2009 - Natural Plant Toxins NST110, Toxicology...

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Natural Plant Toxins NST110, Toxicology Department of Nutritional Sciences and Toxicology, University of California, Berkeley
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Topic outline 1. Goitrogens 2. Cyanogenic Glycosides 3. Licorice 4. Caffeine 5. Digitalis
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Definitions Phytotoxin - is a toxic substance in the plant Allelochemical —plant defense substance that will inhibit growth of other organisms Allelopathy — production of chemicals (allelochemicals) that affect the plants environment
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Goitrogens—goiter producing agents substances that suppress the function of the thyroid gland by interfering with iodine uptake cause an enlargement of the thyroid. Soybeans (and soybean products such as tofu) Pine nuts Peanuts Millet Strawberries Pears Peaches Spinach Bamboo shoots Radishes Horseradish Vegetables in the genus Brassica
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The thyroid hormones act on nearly every cell in the body: 1. increase the basal metabolic rate , 2. affect protein synthesis , 3. help regulate long bone growth (synergy with growth hormone ), 4. neuronal maturation 5. increase the body's sensitivity to catecholamines (such as adrenaline ) by permissiveness . 6. regulate protein , fat , and carbohydrate metabolism , affecting how human cells use energetic compounds. 7. stimulate vitamin metabolism. 8. heat generation in humans. thyroid hormones Thyroid hormones (T 4 and T 3 ) are produced by the follicular cells of the thyroid gland and are regulated by Thyroid-stimulating hormone ( TSH) made by the thyrotrophs of the anterior pituitary gland. The effects of T 4 in vivo are mediated via T 3 (T 4 is converted to T 3 in target tissues; T 3 is 3- to 5- fold more active than T 4 ).
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RXR: 9-cis retinoic receptor Mechanism of Thyroid Hormone Action
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Pathways of thyroid hormone metabolism TRH: Thyrotropin-releasing hormone TSH: thyroid-stimulating hormone thyroxine (T 4 ), triiodothyronine (T 3 )
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Goitrogens—goiter producing agents Hypothalamus pituitary iodide I - iodide I - I 2 iodine thyroglobulin T4/T3 T4/T3 5'-MDI T3 peripheral UDP-GT T3/T4-glucuronide UDP-GT A B C D E O NH S goitrin A. iodide trapping (blocked by thiocyanates (SCN - ), nitrate (NO 3 - ); SCN - is a detox product of CN - ) B. organification (inhibited by goitrin in Brassica plants) C. proteolysis (blocked by excess iodide) D. deactivation (TCDD, PB can induce UDP-GT;UDP-glucuronyltransferase) E. peripheral activation (inhibited by R#3) SCN - , NO 3 - , goitrin lead to hypoactivity of thyroid—less activity of thyroid. Excess iodide can also inhibit proteolysis ; deactivation via UDP-GT can be enhanced by induction of UDP-GT by TCDD, PB deactivate thyroid MDI—inhibited by R#3 produces hyperactive thyroid thyroxine ( T 4 ), triiodothyronine ( T 3 )
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5’-monodeiodinase FDC R#3 in cherries: ADI 0.2 mg/day; EMI=2 mg/day HO 2 C H 2 N H 2 C O I I I OH I T4 produced from thyroid T3 feedback inhibition of pituitary deiodination in peripheral tissue by monodeiodinase O CO 2 Na O I I I NaO I R#3 R#3 inhibits 5-MDI and increases T4 levels so the thyroid stays on Overstimulation causes tumors
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plant toxin 2009 - Natural Plant Toxins NST110, Toxicology...

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