Iodine and polyunsaturates (PUFA) Crucial for the evolution of life

1. Human Evolution: Past, Present & Future. London, 8-10th May 2013 Iodine, PUFAs and iodolipidsin healthand disease: An evolutionaryperspective S Venturi1, CA Castellano2,3 and SC Cunnane2,3 1Servizio di Igiene AUSL - Pennabilli (RN), Italy - Phone: 0541928205 - E-mail: venturi.sebastiano@gmail.com, 2Research Center on Aging, 3Depts of Medicine, Université de Sherbrooke, QC, Canada. • Iodine and polyunsaturates (PUFA) • Crucial for the evolution of life • “Membrane lipid language“ of cells (2) (Figures 1, 2) • Structurally and metabolically synergic • Iodide (I-) – an antioxidant • Electron donor through peroxidase enzymes. • Most ancient inorganic antioxidant in all iodide concentratingcells from primitive marine algae to vertebrates (4,5). Figure 1 - Membrane Chemistry Phospholipids contain one saturated and one unsaturated fatty acid. • Evolution of the thyroid and brain • Origin in the primitive vertebrate foregut • About 500 million years ago, thyroid cells specialized in the uptake and storage of iodo-compounds in the thyroid, a new follicular organ. • At the same time, ectodermic cells differentiated into neuronal cells and became the primitive nervous system (2, 3). • Iodo-lipids • Synthesized by thyroid cells, neurons • Novel “words” of the chemical “lipid language” • Membrane adaptation to the terrestrialenvironment. • Implicated in apoptosis, carcinogenesis, degenerative diseases as well as "(semi)aquatic theory" of human evolution. Figure 2 Lipid language The arachidonic acid pathway to leukotrienes, prostaglandins, and thromboxanes. • PUFA susceptible to peroxidation • Primitive oxygenic and photosynthetic algae, the basis of the marine food chain, accumulatedtrace-elements such as I andSe to protect the fragile PUFAs in their cell membranes against peroxidation (~3.5 billion years ago). • In chemistry, the amount of unsaturation (double bonds) in PUFA is the iodine value or iodine number. • Fish do not synthesize omega-3 fatty acids but only accumulate them by eating algae. • Hypothyroidism in humans • Thyroidectomy or iodine deficient hypothyroidism - metabolic and phylogenetic regression to antecedent reptile stage. • Many symptoms of the hypothyroid humans seem to be reptile-like: dry, hairless, scaly and cold skin with a general slowdown of metabolism, digestion, heart rate, nervous reflexes, lethargy and hypothermia (6). • Amphibian metamorphosis • I and T4 stimulate the spectacular apoptosis (programmed cell death) of the cells of the larval gills, tail and fins • Transforming the aquatic, vegetarian tadpole into the terrestrial, carnivorous frog with better neurological, visuospatial, olfactory and cognitive abilities for hunting (6). • Contrasts with neotenic amphibian salamanders, which, without introducing iodine, don’t transform in terrestrial adults and live and reproduce in the larval form of aquatic axolotl. • Antioxidant mechanism of iodides • 2 I- → I2 + 2 e- (electrons) = - 0.54 volts • 2 I- + peroxidase + H2O2 + 2 tyrosine → 2 Iodo-tyrosine + H2O + 2 e- (antioxidants) • 2 e- + H2O2 + 2H+ (of intracellular water-solution) → 2 H2O • 2 I- + peroxidase + H2O2 + tyrosine, histidine, lipids, carbons → iodo-compounds + H2O + 2 e- (antioxidants) • Iodo-lipids: • DHA - iodolactone (5-iodo-4-hydroxy-7,10,13,16,19- • docosapentaenoicacid, gamma-lactone) and • AA – iodolactone (6-iodo-5-hydroxy-8,11,14-eicosatrienoic acid, • delta-iodolactone). Biodistribution of radio-iodine in the human Sequence of 123-iodide total-body scintiscans of a woman after intravenous injection of 123-iodide (half-life: 13 h); (from left) respectively at 30 min, and 6, 20 and 48 h. The highest and most rapid concentration of radio-iodide is in stomach, salivary glands, CSF, choroid plexus and oral mucosa. In the thyroid, iodide is more progressive, as in a reservoir (from 1% after 30 min to 5.8 % after 48 h; Venturi, 2007). Biodistribution of radio-iodine in the rat Distribution of 131-iodine (half-life - 8 d) in autoradiographs of the rat after subcutaneous injection of 131-iodine. High I concentration is evident in iodo-compounds and iodo-lipids of the choroid plexus, retina, hypothalamus, gastric mucosa and epidermis, where it is detectable up to 5 days after injection (courtesy of Path Biol, 1961; Acta Radiol Ther Physics Biology, 1964). REFERENCES (1) Venturi S. (2013). Iodine, PUFAs and iodolipids in health and diseases: an evolutionary perspective. Accepted for publication in Nutr Health (2) Crawford, M. A. (2010). The language of lipids. In: Cunnane S, Stewart K, Eds. Human Brain Evolution, The Influence of Freshwater and Marine Food Resources. Wiley-Blackwell, NJ, 2010,: 13-28. (3) Cunnane, S. (2010). Brain-Selective Nutrients. In: Cunnane S, Stewart K, Eds. Human Brain Evolution, The Influence of Freshwater and Marine Food Resources, Wiley-Blackwell , NJ, 2010: 33-61 (4) Küpper, F.C., Carpenter, L.J., McFiggans, G.B., et al. (2008). "Iodide accumulation provides kelp with an inorganic antioxidant impacting atmospheric chemistry". Proc. Natl. Acad. Sci. U.S.A. 105 (19): 6954–8. (5) Packer, L. (2008). Oxidants and Antioxidants in Biology. XIV Biennial Meeting of the Society for Free Radical Research International; October 18-22, 2008. Beijing (China).* (6) Venturi, S. (2011). Evolutionary Significance of Iodine. Current Chem. Biol., 5 ,3 :155-162.