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Potassium in a Nutshell

Potassium in a Nutshell. Mineral Mineral Interactions. Rule : Seldom will one mineral function in isolation apart from other minerals.

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Potassium in a Nutshell

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  1. Potassium in a Nutshell

  2. Mineral Mineral Interactions Rule: Seldom will one mineral function in isolation apart from other minerals

  3. The negative interaction of metal ions is one of the major dietary factors that causes low bioavailability of these nutrients. Interactions of nutritional significance include sodium-potassium, calcium-magnesium, manganese-iron, iron-copper, and zinc-copper. These interactions reach potential importance when the first metal of each pair listed above is in excess and the other is at the lower limit of requirement. The trace element interaction of highest practical significance in human nutrition is the negative effect of excess zinc on copper bioavailability. O’Dell, 1989

  4. Trace elements sharing absorptive pathways compete for uptake, and imbalances in the ratios between trace elements (Fe/Zn, Zn/Cu, Fe/Mn) in formulas may impair trace element absorption. These factors need to be taken into consideration when setting upper limits for trace elements in formulas Lonnerdal, 1989

  5. Guidelines for essential trace element preparations for parenteral use. A statement by an expert panel. AMA Department of Foods and Nutrition. • [No authors listed] • PMID: 107339 [PubMed - indexed for MEDLINE]

  6. How do Minerals fit into life? The two “Inters” Interlinked Interdependence

  7. K Mg P I Cr Ca

  8. 1s22s2 [Be] 1s22s22p1 1s22s22p6[Ne] Ne (3s2) Ne (3s23p6) [Ar] Ar (4s2) Mineral Mineral Interactions Macro Symptom Comment Na – K Hypertension K reduced hypertension Ca – P Skeletal growth Diet 1.0 – 1.3 considered ideal because endogenous P is high Ca – Mg Soft tissue calcification High Ca blocks Mg absorption P – Mg Growth rate retarded High P also blocks Mg absorption No interaction 1s2 Mg K Ca P Na No interaction Why do we know so much more about Ca interactions with other minerals?

  9. 7 6 5 4 3 2 1 0 3.2% Ca, 0.8% P Guinea Pigs Daily Wt gain (g) 0.9% Ca, 0.8% P (normal) 2.5% Ca, 1.7% P 1 g/kg 2.4 g/kg 4.0 g/kg 0 30 60 120 180 240 360 600 1200 Mg K Log of Dietary Mg (mg/100g) Ca O’Dell and Morris, 1963 P Na

  10. =O3PO OPO3= H OPO3= H H Fe Mn Phy-P =O3PO H =O3PO OPO3= Ca Phytic Acid (phytate) Zn Se Cu I Mo S S S S S Cu Mo Mo S S S S Micro-mineral Interactions Tetrathiomolybdate

  11. Human Studies Iron impedes Zn absorption in human subjects. Subjects given 12 mg Zn and the indicated amount of iron in an aqueous solution. Zinc Absorption Iron has no significant effect on the absorption of Cu by human subjects. Subjects given 3 mg Cu and the indicated amount of iron in an aqueous solution. Copper Absorption Conclusion: Oral Fe supplements may impair zinc absorption in a dose-dependent manner, but have no effect on Cu absorption Iron (mg) Troost et al, Am J. Clin Nutr, 2003

  12. Zn –Cu Interactions in Chicks (O’Dell, 1967) 500 450 400 350 300 250 200 150 100 Body Wt.(g) Zn Supl. Cu Supl. -- + -- + -- + 28 28 84 84 140 140 Mg/Kg

  13. Human Studies Hypocupremia induced by zinc therapy in adults. Prasad AS, Brewer GJ, Schoomaker EB, Rabbani P. JAMA 1978 240:2166-2168 Hypocupremia occurred in an adult with sickle cell anemia who received zinc as an antisickling agent for two years. The hypocupremia was associated with microcytosis and relative neutropenia. Administration of copper resulted in an increase in RBC size and leukocyte counts. We have since observed hypoceruloplasminemia of varying degrees in several other sickle cell anemia patients who were receiving oral zinc therapy. This complication was easily corrected by copper supplementation.

  14. Fe Mn Phy-P Ca Zn Se Cu I Mo S Excessive intake of Mn interferes with Fe metabolism. And, excessive amounts of unbound Fe intracellularly interferes with Mn incorporation into enzymes.

  15. Implications of Mineral-Mineral Interactions Intracellularly Dilemma That certain metals compete with other metals in an antagonistic fashion raises the question as to how does the correct metal congener and not the look-alike antagonist find its way into an enzyme? What effectively eliminates mistakes in metal selection at the level of protein binding? Candidates: Metallochaperones Effective sequestration

  16. Many metalloproteins can bind diverse metals, but living cells connect only with their cognate metal cofactor. In eukaryotes, metal specificity can be achieved through metal-specific metallochaperone proteins. Yeast Mn superoxide dismutase (SOD2) binds Mn over Fe. Preference is determined by the relative bioavailability of these 2 ions within the mitochondria. Normally, most mitochondrial Fe is unavailable to SOD2. But, when yeast have mutations in the genes that transport and store Fe, Fe accumulates in a reactive form that potently competes with Mn for binding to SOD2, inactivating the enzyme. Under normal circumstances, a small pool of SOD2-reactive Fe exists in homeostasis with bound Fe and has access to SOD2 when mitochondrial Mn is low. Controlling this reactive Fe pool is critical to maintaining SOD2 activity and has important potential implications for oxidative stress in disorders of Fe overload.

  17. Fe Storage FeSOD Fe MnSOD Fe Fe MnSOD X Fe Fe Vesicle transporter Mn X Fe Mn Iron chaperone Mn Fe Fe Fe

  18. Fe Mn Phy-P Ca Zn Se Cu I Mo S

  19. Cu/Fe Interactions Summary of Key Observations: Yeast cells lacking Cu are unable to transport iron Iron fed to anemic rats only partially restored hemoglobin levels in the blood. An ash of alfalfa resulted in full restoration as did copper salts Cu deficient animals accumulate stores of iron in the tissues Cu deficiency lowers the level of enzymes that oxidize iron, viz., ceruloplasmin, Fet3 in yeast

  20. 1 1 2 2 3 3 4 4 Fet3p-Ftr1p in Yeast Fet3p-Ftr1p high-affinity Fe-transport (permease) complex. Fet3p, a Cu oxidase, couples with Ftr1p permease at the Golgi and moves to the plasma membrane as a functional complex for Fe(II) uptake. 4 Cu atoms are loaded into Fet3p by Ccc2p , a Cu-ATPase. Cl- ions from Gef1p Cl- channel protein provide the Cl-. Fe(III) After Labbé and Thiele, 1999

  21. Multicopper Oxidases with Ferroxidase Properties 4Fe2+ + O2 + 4H+ 4Fe3+ + 2H2O • Plasma ceruloplasmin • Membrane-bound ceruloplasmin • Hephaestin • Fet3p • Fet5p • 200,000 Mwt ceruloplasmin • 120,000 Mwt ferroxidase in liver

  22. Tissue Iron Accumulation and Retention in Aceruloplasminemia 59Fe Logan et al, 1994

  23. Fe Mn Phy-P Ca Zn Se Cu I Mo S A slight excess of Cu (or Zn) has no effect on Se A large excess (100 times) of Cu or Zn has been shown to cause exudative diathesis in chicks that was corrected by Se supplementation. Absorption across the intestine is not a factor, but rather internal distribution of Se to the various organs

  24. Fe Mn Phy-P Ca Zn Se Cu I Mo S Na2SO4 competes with Na2SeO4, as shown by the SO4 inhibiting the action of the SeO4 in correcting white muscle disease in lambs. Puzzling: K2SO4 added to selenomethionine or selenocysteine, the 2 most common dietary sources of Se, did not accentuate the signs of Se deficiency in lambs.

  25. Serine Absorption Serine-tRNA ATP [HSe-PO3] Selenoprotein (GPx, etc) SeO3 [Se]cysteine-tRNA Assimilation SO4 [Se]cysteine-tRNA [Se]cysteine Selenium Incorporation into Protein [Se]methionine [Se]methionine-tRNA Ionic radii: Se = 1.9 nm S = 2.0 nml Covalent radii: Se = 1.03 nm S = 1.07 nm

  26. Fe Mn Phy-P Ca Zn Se Cu I Mo S Selenium is required for the enzyme Iodothyronine Selenodeiodinases

  27. Evaluation of influence of selenium, copper, zinc and iron concentrations on thyroid gland size in school children with normal ioduria Brzozowska M, Kretowski A, Podkowicz K, Szmitkowski M, Borawska M, Kinalska I. June, 2006 In spite of proper iodine prophylaxis, there was a 7% rate of goiter occurrence in school children suggesting factors other than iodine deficiency influence goiter development. Low concentration of Fe and/or Se were found in the serum of children with goiter in spite of their treatment with thyroxine. There may be additional factors influencing the effectiveness of this treatment.

  28. Iodine and selenium deficiency in school-children in an endemic goiter area in Turkey. Aydin K, Kendirci M, Kurtoglu S, Karakucuk EI, Kiris A. 2002 Endemic goiter is one of the most important health problems in Turkey. The effects of iodine and Se levels on thyroid gland size and thyroid functions is the objective. Of 73 healthy children 7-12 years old, 38 girls and 35 boys, 32 (43.8%) showed goiter by palpation, 56 (76.7%) by ultrasonography. Serum T3 and TSH levels were in the upper normal range, and T4 was normal, but thyroglobulin was higher than normal. Serum Se was 30.84 +/- 23.04 microg/l, and urinary iodine was 3.91 +/- 3.77 microg/dl, appropriate for moderate iodine and Se deficiency. Thyroid volumes correlated negatively with Se levels, and not at all with urinary iodine and thyroid hormones. In conclusion, children in this area had significant goiter problems, probably due to the iodine as well as Se deficiencies.

  29. Selenium and the Control of Thyroid Hormone Metabolism Aug 2005, Vol. 15, No. 8 : 841 -853 Josef Köhrle Thyroid hormone synthesis, metabolism and action require adequate availability of iodine and Se, which affect homeostasis of thyroid hormone–dependent metabolic pathways. The three selenocysteine-containing iodothyronine deiodinases constitute a novel gene family. Se is retained and deiodinase expression is maintained at near normal levels in the thyroid gland, brain and other endocrine tissues during Se deficiency, thus guaranteeing adequate levels of T3 the active thyroid hormone. While some Se enzymes are impaired in patients with cancer and other disturbances, Se-dependent deiodinase function might still be adequate. However, Se status could be responsible for altered thyroid hormone metabolism. Limited or inadequate supply of iodine and Se leads to complex rearrangements of thyroid hormone metabolism enabling adaptation to unfavorable conditions

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