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107 Cards in this Set
- Front
- Back
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Trace Element Essentiality |
When its lack results consistently in a reduction of a physiologically important function If it is an integral part of an organic structure performing a vital function in that organism |
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Is a mineral element normally volatilized? |
Cannot be decomposed to simpler substances |
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Physiological roles of trace elements |
Regulatory Structural Protective |
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Regulatory roles of trace elements |
Metalloenzymes Enzyme activators Affect DNA expression |
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Structural roles of trace elements
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Membrane integrity Bone structure |
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Protective roles of trace elements |
Antioxidant defense Immune defense |
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Zinc Functions |
Enzyme activator Metalloenzymes Host defense and immune system competence Nucleic acid synthesis structural components |
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Manganese functions |
Enzyme activator Metalloenzymes Structural components |
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Selenium Functions |
Metalloenzymes Host defense and Immune system Enzyme Activator |
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Iron Functions |
Metalloenzymes Host defense and Immune system Respiratory carriers Enzyme activator |
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Copper Functions |
Structural Components Respiratory carriers |
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Fluoride Functions |
Structural components |
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Cobalt functions |
In vitamins |
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Iodine functions |
In minerals |
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Are they important quantitatively? |
Occur and function in vivo at low concentrations |
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Wilson's Disease |
Cu toxicity |
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Menke's kinky hair syndrome |
Cu deficiency |
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Acrodermatitis enteropathica |
Zn deficiency |
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Hemochromatosis |
Fe toxicity |
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Hereditary Manganism |
Mn |
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Zn Deficiency |
Anorexia (decreased eating) Hypogeusia (decreased taste) Growth retardation Hypogonadal dwarfs |
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Cu deficiency |
Socially deprived Undergoing rehab. |
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latent deficiency |
Trace elements can influence human health without necessarily producing diagnostically specific clinical changes Usually contingent on stress, infection, malnutrition, etc. |
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Advances in trace-element analytical techniques since 1973 |
Accuracy of analysis Certification of reference materials Reliable monitoring of concentrations in foods Foods enriched in trace elements (infant foods and TPN formulas) Centers of trace element research International reference laboratories- National diets Advances in molecular genetics/biology |
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Essential trace elements |
Needed in mg amounts Zn, Fe, B, F, Mn, Ni, V |
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Transition metals |
Divalent cations have unfilled d orbitals Mn= d5 Co= d7 Cu= d9 Form coordinate covalent bonds with ligands that contain the electron-donor atoms N, O, S found in proteins |
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Coordinate covalent bonds |
Bonds between two atoms in which both electrons shared come from the same atom |
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Trace element analysis |
Measure total quantity in accessible tissues and body fluids Measure the activity of trace element dependent enzymes Can use combination that reflects total body trace element content and/or tissue stores. |
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Assessing Nutritional status of Trace Elements |
Blood- Trace element content of blood- not true indicator/ severe deficiency Liver biopsy Hair (Zn) Bone- sensitive (Ca, Zn, F) Urine- transition elements insoluble- effective with I, Se, F, Cl. Cd toxicity |
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Tools available for analysis |
Atomic Absorption Spectrometry (most widely used)(ppm) Graphite furnace AAS (ppb) Neutron Activation analysis |
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Atomic Absorption Spectrometry (AAS) |
Analytical procedure for the quantitative analysis of trace elements utilizing the absorption of optical radiation (light) by free atoms in the gaseous state Element is atomized and then irradiated by an optical source |
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Problems with analysis |
Contamination Hard to deplete due to stores or slow turnover (2-3 generations). Use antagonists. Problems in developing diets. Select ingredients to be low in the nutrient under study |
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Ligand |
Structures which permit simultaneous attachment to a cation |
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Chelates |
compounds which contain chelate rings and function to fasten to a central metal atom so as to produce heterocyclic rings |
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Donor anions |
O, N, S most common in body |
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Acceptor cations |
Transition elements V 3+, Cr 3+, Fe 2+, Cu 3+, Zn 2+ |
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Chelation |
shields metal ion from external influences Highly stable Presence of metal alters chemical and physical characteristics |
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Organic Chelates |
May be the most important factor controlling absorption of these minerals (bio availability) Hemoglobin (Fe) Vit B12 (Co) |
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An element can be chelated by a compound that: |
would release it in its organic form or it would be readily absorbed as in an intact chelate Both of these would increase the absorption of the element by preventing its conversion into an insoluble chemical compound. |
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Chelates with high stability |
metal ion is released with great difficulty, so it may be nutritionally unavailable. |
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Highly absorbent chelates |
may prevent metal ion from forming insoluble metal complexes |
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Types of chelating agents |
Proteins and amino acids Carbohydrates, ascorbic acid Nucleic acids |
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Most important type of chelating agent |
Proteins and amino acids |
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Differences in chelating agents |
Each agents has a specific stability constant which is different for different trace element EDTA has much stronger affinity for trace elements than AA |
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Transferrin |
Synthesized specifically for iron transport |
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Stability constants |
The affinity of a chelate for a metal ion may be expressed quantitatively as a stability constant |
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A chelating agent may: |
Perform useful and vital functions in the body or: Others may cause interference with metabolism |
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Effects of chelating agents depend on |
Stability Constant Absorbability Relative ease with which the metal may be released from the chelating agent |
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Chelation equation |
L + M++ -><- MC complex |
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Kf |
log Kf= stability constant Kf = [MC]\ [M++][L] Kf represents number of moles of a chelated metal ion in relation to the product of the number of moles of a metal ion and of ligand remaining in free site. The metal ion having a high stability constant may replace the metal ion of lower stability constant n a chelate |
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Three types of chelates |
Transport and storage of metal ions Essential in metabolism Chelates which interfere with utilization of essential cations |
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Transport and storage chelates |
metal does not modify ligand property requires ligand for absorption AA-metals: very good because of Nitrogen's unpaired e- EDTA-Zn improves its availability |
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Essential metabolism chelates |
metal ion present in chelate in order to perform its function (Hb, B12) |
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Interfering chelates |
Formed by accident no useful biological value Phytic acid- Zn may interfere with normal metabolism |
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Phytic acid and Zinc |
Since phytic acid can form a chelate with zinc, it can reduce absorption of Zn Fruits and veggies are high in phytic acid, so vegetarian diets can lead to deficiency in Zn due to this interaction |
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What factors effect the chelate? |
Size of ring Number of rings Ligand basicity Steric Effects Type of coordinating group Entropy |
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Size of chelate ring |
5-6 membered rings give optimum stability constants |
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Number of chelate rings |
Increase in number increases stability of species |
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Ligand basicity |
Greater the basicity of the donor group the greater the stability |
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Steric effects |
Attached group on ligand |
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Entropy |
Randomness Changes chemical stability of a compound depending on ring number. Large number of rings results in greater entropy. |
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Importance of chelation |
To transport and store metals Biological function; Hb is an Fe chelate; B12-Co Nutritional aspect -May be detrimental, makes element unavailable -may increase availability. Acute lead toxicity, infuse i.v. EDTA- small molecule is cleared by kidney |
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Bio availability |
degree to which the body is able to use a substance in the form or amount present |
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Absorption of minerals |
varies from 5-95% |
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Factors affecting bioavailability |
Dietary composition Mineral interactions Chemical form of mineral in the diet Gastrointestinal secretions health of host Medications Luminal interactions |
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Dietary factors affecting bioavailability |
Chemical form-heme-Fe and other non-heme-Fe forms Fiber, phytic acid, and tannins - harmful Proteins- free peptides or AA- beneficial Ascorbic acid- due t its reducing potential- beneficial Mineral-Mineral Interactions Food Processing- less or more available i.e. removing germ in wheat = less available |
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Mineral bioavailablity can be altered by factors that affect: |
Absorption Excretion Storage Transport of minerals |
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Definition of Bioavailability |
Proportion of the total trace element in the food that is utilized for normal body functions (biochem or physiologic) and depends initially on the chemical form that is presented to the GI cells % bioavailability = % absorption x % assimilation x 10-2 |
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Assimilation |
proportion of the nutrient available for metabolic function. Proportion used or utilized after absorption |
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Assimilation is based on |
Transport- how much Cellular uptake- how much take up by cells Incorporation into a molecular active form i.e. Metalloenzyme, ion channel, structural unit. |
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Three levels bioavailability is determined at |
Absorbability Mucosal and serosal transfer Utilization |
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Absorbability |
proportion available in the lumen for uptake into the mucosa cells |
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Mucosal and serosal transfer |
transfer into systemic circulation is controlled by physiological factors |
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Utilization |
within the body is influenced by physiological factors and is also affected by the chemical form of the absorbed substance |
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Effect of increased pH on absorbability |
increased pH = increased precipitation of trace minerals which yields decreased absorbability. |
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Bioavailability of an element is affected overall by: |
Intrinsic or inherent physiologic factors and extrinsic or dietary factors |
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Intrinsic factors |
Age- bioavail decreases as we age Sex Genetics Nutritional status Physiological status- health and disease, GI disorders Physiological stress- pH, hormones, mechanical motility. |
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Methods to assess mineral bioavailability |
Chemical balance Rate of repletion following depletion (unethical with humans) Plasma appearance following ingestion- big oral dose Radioisotopes-label food with radioisotope- deduct fecal and urinary excretion Stable isotopes |
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Chemical balance |
trace elements intake and excretion is quantitatively measured over a fixed time-period-limited for bioavailablity studies |
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Radioisotope techniques |
Fecal monitoring Whole body retention (gamma-emitting isotopes) Plasma appearance Urine appearance |
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Stable isotopes |
naturally occurring nuclides of an element with the same atomic number but differeing number of neutrons similar chemical properties but differ in mass Mass spectrometry (Thermal Ionization Mass Spectrometry) and neutron activation analysis |
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Insolubility and minerals |
key marker of the potential bioavailability of a mineral |
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Solubility and minerals |
refers to solubility of an ion, salt, hydrate or complex. Also refers to the type and strength of chemical bonds involved |
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Solubility product |
As pH increases, largely insoluble mineral hydroxides form, which are in equilibrium with the metal ion Increase in pH or [OH] causes a decrease in free metal ion |
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Enhancers |
molecular species found in foods that form a compound with the mineral that is solble and can be absorbed by mucosal cells or that it is cleaved to release the mineral in a soluble form or have stability constants which allow the mineral to be transferred to a mucosal or serosal acceptor |
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Examples of enhancers |
Citric acid: Zn-binding ligand in human milk. Aids Ca absorption EDTA (Zn) Histidine (Zn) Stability constants of an enhancer with a metal must be somwehere between that of the inhibitor and the compleing agent in the body |
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Enzyme-metal interactions |
Electrochemical Structural Catalytic |
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Electrochemical Interactions |
Occur as free ions (Ca, Cl, K, Mg, N, Na, P, S) Source of energy during cell stimulation Stabilize emulsions of highly charged colloidal particles which are present Neutralize charges on acidic molecules such as free carboxylic acids (nerve conduction, muscle contraction) |
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Structural interactions |
F, Fe, Mg, Si, Sr, P, S, Bo, Ca Proteins Nucleic acids Phospholipids Carbohydrate derivatives Cell membrane- plant cells Hydroxyapatite- Bone |
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Catalytic (Cofactor) |
Ca, Cl, Co, Cu, Fe, Mg, Mn, Mo, Zn, Na, P, S 1/3 of all enzymes involve a metal ion as an essential participant |
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Active site function |
Metal ion may serve to lock the geometry of the active site so that only certain substrates can be accommodated Metal ion is responsible for maintaining tertiary and quartenary structures of an enzyme (protein) |
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Removal of metal ion from active site |
Causes denaturation or dissociation into subunits and the disintegration of the active site. |
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Allosteric effect |
Primarily structural effect Despite distance, metal ion modifies substrate-binding by inducing conformational changes at active site |
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Bridge |
Metal ion acts as a bridge It forms an active intermediate i.e. Mn(II) arginase-E-M-S (Enzyme-metal-substrate) |
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Coenzyme |
Metal ion may bind both coenzyme and substrate to the active site or it forms a bridge |
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General Equation |
Enzyme + Substrate <--> Ezyme Substrate complex <--> Product + Recycled Enzyme |
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General Equation with metal |
E + Metal <--> EM + S <--> EMS complex <--> P + EM <--> E + M |
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E-M-S complex |
Conformational changes Decreases energy of activation allows Reaction to occur more readily |
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Three basic complexes that may form |
E-M-S (metal bridge) E-S-M (substrate bridge) M-E-S (Enzyme bridge) |
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Relationships of metals and enzymes |
Strength of the association between metal and protein can be characterized by their stability constants Stability constants are direct functions of the firmness of metal binding |
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Metal-activated enzymes |
Metal may be removed from protein during isolation and metal free protein may show same activity Metal is loosely associated with the protein but it is essential for maximum activity of the enzyme Lesser degree of specificity in vivo vs. in vitro |
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Metalloenzymes |
Show no evidence of dissociation under physiological conditions Very hard to remove metal ion- complete loss of activity May restore activity by addition of original metal Addition of different metal will not reconstitute activity Thus, interaction between active metal and apo-enzyme must be highly specific and unique |
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Different Metalloenzymes |
Carboxypeptidase Yeast alcohol dehydrogenase Liver alcohol dehyrogenase Alcaline Phosphatase |
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Carboxypeptidase |
Contains one atom Zn/ mole enzyme Peptidase and enterase activity If purified and dialyzed against a chelating agent Zn comes off and activity is destroyed If add Zn back in solution, restore enzymatic activity. Zn has catalytic function No alteration in structure of enzyme following removal of metal |
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Yeast alcohol dehydrogenase |
Contains 4 Zn atoms/ mole enzyme Zn atoms perform both structural role and catalytic role When chelated Zn with chelating agent; end up with four subunits After adding Zn back cannot reconstitute enzyme activity because lost structural Zn |
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Liver Alcohol dehydrogenase |
Contains 4 Zn atoms/ mole enzyme Two active sites Two zn atoms are catalytic- are easily accessible and can be removed by chelating agents Remaining two are bruied and are necessary for maintaining enzyme structure |
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Alcaline phosphatase |
Contains 4 Zn atoms/ mole enzyme Two structural and two catalytic All atoms can be removed without bringing about change in subunit structure Could use Co to sub for Zn Co has its own spectral properties |
