week 8- micronutrients Flashcards
• trace elements:
o essential: Cr, Co, Cu, I, F, Fe, Mn, Mo, Se, Zn
o NE: Ni, Si, Sn, V, B, Li
o Content in plant foods depends on soil content
o difficult to quantify biochemically
o Bioavailability influenced by other diet factors (esp other minerals)
• First basic law of nutrition:
o No nutrient is absorbed and utilized to the full extent that it is consumed
• Bioavailability
o May refer to either % nutrient ingested or % absorbed
o ingested preferred
o absorbed hard to determine, need indirect analysis; more accurate
o BA= a post-absorption assessment of % absorbed that becomes functional to the system
o Absorptive and assimilation phases
• Important for mineral absorption:
o Acidic pH of stomach: dissociation of minerals from food protein-bound state
o Pancreatic HCO3 neutralizes acidic chyme → form mineral complexes w organic acids & (-) charged amino acids (Ca aspartate, Mg oxalate)
o → ↑ absorption
• Slop ratio method:
o Asses bioavailability
o Ex: measure bodyweight of growing chicks
o ↓ BW will show when nutrients are ↓BA
o Steeper slop means more BA
• Balance approach:
o “keeping the status quo”
o Match input w excretion: balance, (+) growth, or (-) wasting
o Assess ability to: store, recover loss of turnover, delay appearance of clinical signs
o Problems: endpoint, time critical, can’t look at past exposure/adaptation
• Absorption/excretion vs retention
o Ex: 2-picolinic acid ↑ Zn absorption in rats by 60%
o But also ↑ excretion
o So no net effect on RETENTION
o hence no ↑ BA
• Why Not Absorption Alone as an index of Bioavailability?
o Assimilation major part of mineral’s BA, need assess separately
o Ex: only 0.5/5 mg X absorbed (10% absorption)
o → 0.21 mg absorbed becomes functional (42%)
o = only 4.2% of ingested is assimilated (vs 10%)
• Functional Response to Mineral Intake
o ↓Intake: Def state → interfere w enzyme activity & structural protein integrity
o ↑Intake: mb → toxicity; Any element mb harmful if body’s intake exceeds ability to use/store/excrete
o Optimal: Max fxn enzyme systems, structural proteins, etc; min toxicity potential
• Optimal Intake Approach for Assessing Requirement:
o Intake should: optimize physical/mental performance, tx dz, ↑longevity
o Problem: “should duplicate human milk”- too general, Defies population-based approaches
• Population/clinical approach:
o Link dz state & structural/fxn abn w known biochemical/fxn changes
o Parameters:
o Growth rate
o Physical appearance (skin, bone, hair, etc)
o Physiological impairments (GI, immune, nervous)
o Cognitive fxn
o Biochemical impairments (stress, enzymes, metabolic)
o Medical (prone to dz)
• Traditional Approaches to Determining Mineral Status:
o Body stores of mineral
o Overt response to ↑ mineral intake
o Phsy signs def: Stunted growth, Overt abn
o Internal signs def (biomarkers): Tissue/blood levels, Mineral binding proteins levels: Fxnal Assays, Enzyme assays
• Biomarkers; Ex: Body stores of a mineral:
o Ideal: reliable internal factor, responds directly, specifically, quantitatively to changes in a mineral’s homeostasis
o Applies mainly to Fe:
o Circulating ferritin = measure of Fe tissue stores
o Total iron binding capacity (TIBC)
o Transferrin saturation
o HCT, Hb, RBC morphology
• Blood/plasma mineral status assessment:
o Serum/plasma: “most popular” for element status, mb NOT accurately reflect whole body mineral status
o Whole blood: Best for STAT determinations of Na & K; mb for toxic metal poisoning
o RBCs & WBCs: Intracellular mineral content mb BEST correlation w nutritional status
• Urine, hair mineral stat assess:
o Urine: Excretory aspect of mineral balance, if renal fxn is adequate; daily dietary intake shold be constant to reflect nutritional adequacy
o Hair: Essential elements = controversial. Mb screen for heavy metals. ↑ metabolic activity and sulfhydryl group concentration concentrate heavy metals up 100x blood levels
• Functional indices:
o ↓ intake of some minerals → disrupt biochemistry: ↓enzymes, hormones, alt tissue morphology
o Important: direct connection bw mineral in question and fxnal component
o Ex: suspect I def → check T4
o Fe def → Hb
o Sel def → glutathione peroxidase
• Iron, from diet to blood:
o Fe2+ and Fe3+ insoluble, need special transporter
o Food Fe mostly Fe3+, tightly bound to organic molecules
o Stomach acid: Fe can dissociate
o → react w fructose, ascorbic acid, citric acid → soluble in intestine fluid
o DMT1 (divalent metal transporter 1): moves Fe across intestinal cells, store as ferritin (Fe3)
o Must reduce to Fe2 to release from ferritin
o → oxidized to Fe3 via ferroxidase ceruloplasmin → transferrin → body
• Iron in blood:
o Purpose: O2 transport by Hb
o Apoferritin assimilates up to 4,300 Fe to form Fe storage protein ferritin
o Ferritin → available storage form for Fe in RES
o Apotransferrin (apoTf): protein, can bind 2 Fe → transferrin, Fe carrier in plasma
• Daily Fe turnover:
o Absorb 1-2 mg
o → plasma transferrin, 4 mg → myoglobin (4 mg)
o → RBCs (BM, 20 mg), RBCs 2.5 g, RBCs (RES, 20 mg)
o Body stores: 1000g (M), 300-500g (F)
o → excrete (GI, stool) 1-2 mg
• IDA:
o Hypochromic microcytic; o Occasional Target cells o Pencil shaped poikilocytes o ↓ reticulocytes o Transferrin/TIBC: Normal to High o Serum ferritin: ↓ (Very low)
• Ferritin plasma, stores, problems:
o Most sensitive indicator of iron stores
o Adults: 1ug/L plasma = 8 mg stored Fe
o ↓ 12 ng/L = no Fe stores
o Kids: 1 ug/l = 14 mg stored
o Avg M: 112 ug, F: 36, Kids: 23
o Acute phase protein
o ↑ in: inflame, infx, dz (CA esp colon, CV), EtOH, hyperglycemia, obesity
• Transferrin saturation:
o TIBC (total iron binding capacity) o UIBC (unsaturated iron binding capacity) o 33% normal, 47% in AM (after fasting), 13% at night
Soluble transferrin receptor conc of plasma
o New concept, good index of early Fe def
o Basis: cells that need Fe express transferrin recpetors
o Extracellular domain of receptors released into plasma
o # receptors in plasma proportional to # expressed on cell surface
o = measure of Fe requirement
• Iodine:
o body normally has 20-30 mg, > 75% in thyroid
o rest in mammary gland, gastric mucosa, blood
o main known fxn: thyroid hormone
• Iodine balance:
o Absorbed as iodide (I-)
o both free and protein-bound in circulation
o stored in thyroid
o T4 degraded in target cells and liver → I conserved if needed
o excretion primarily via urine
o small amounts from bile →feces
• Iodine def:
o → goiter (mc F, ↑age)
o Absolute: def (endemic areas)
o Relative: adolescence, pregnancy, lactation
o repletion must be done slowly to prevent hyperthyroidism
• Iodine excess and toxicity:
o Humans very tolerant to high dose
o Paradoxical goiter: enlarged thyroid dt ↑↑ dose I
o Japan and China w ↑ intake seaweed (50,000 - 80,000 mg/day)
• Iodine assess:
o Urine: Standard method to assess I status and intake worldwide
o > 90% excreted in urine
o Random urine samples adequate for screening
o ZRT: dried spot sample urine
• Thyroid fxn tests:
o Biomarkers: long-term I intake and status
o TSH ↑ in I def
o Serum Tg correlate w urine I levels
o ↓T4 w ↑T3 may indicate I def
o ZRT: comprehensive blood spot test (Tg, TSH, T3, T4, TPO)
• Iodine skin patch:
o Not reliable form of I absorption
o Oral much better
• Zinc, Roles:
o 300 enzymes assoc o Fxns: Catalytic, Structural, Regulatory o Protein synthesis o Nucleic acid metabolism o Carb and energy metabolism o Lipids o Epithelial tissue integrity o Cell repair and division o Vitamin A and E transport and utilization o Immune fxn o Reproductive hormones
• Zn stores (%):
o Whole body: 1.5g (F)-2.5g (M) o Skeletal Muscle 57% (250 d) o Bone 29% (7 yrs) o Skin 6% o Liver 5% o Brain, Kidneys, Heart o Only 0.1% plasma, so plasma Zn mb not good measure
• Zinc storage:
o No specific storage sites
o in cells, sequestered in metallothionEIN (mb considered stores)
o Anorexia, muscle catabolism, tissue Zn release → Metalloenzymes cling tenaciously to Zn
o turnover extensive and rapid: fast ~12.3 d, or slow ~300 d
o Fast = “exchangeable” pool, 157-183 mg
• Zn regulation:
o Metallothionein: Conc in liver, kidney, pancreas, intestine
o Zn2+ buffer, Controls free Zn2+
o Control intracellular Zn pool (dt hormones and diet)
o ↑ in cellular MT → ↑ Zn binding in cells
o Acute infx (proinflam cytokines) ↑ Zn uptake into liver, BM, thymus, ↓amount to bone, skin, intestine (plasma Zn falls)
• Zn excretion:
o hair, sweat, desquamation, bile, seminal fluid, urine, feces
o endogenous: Bile and pancreas secretion; Mucosal cells
o Urinary and integumental: normal ↓20%; ↑ w trauma, muscle catabolism, chelating agents (EDTA)
o Primarily in feces: Unabsorbed Zn, Secreted Zn (endogenous)
• Zn def:
o ↓Growth
o Delayed sexual maturation, impotence, Impaired testicular development, Hypogonadism, hypospermia
o Alopecia, Acro-orifical skin lesions, glossitis, nail dystrophy
o Immune deficiencies
o Behavioral changes
o Night blindness
o Impaired taste (hypoguesia)
o Delayed healing of wounds, burns, decubitus ulcers
o ↓appetite & food intake
o Eye lesions, photophobia & lack of dark adaptation
• Other Zn indicators:
o carbonic anhydrase: but no turnover o Hair Zn. Good marker perhaps. o Zinc Excretion (urine and feces) o Tissue stores o Zn-dependent enzymes: ALP, SO.D… o Zn response to supplements
• Selenium:
o In glutathione peroxidase (intracellular antioxidant)
o Needed for conversion of T4 → T3
o Selenoproteins: catalyse redox rxns, oxidative stress (M0, N), UV in sunlight
o food content depends on soil
o Plasma Selenium (8-10 g/L) considered sensitive and specific
o Def: Keshan’s dz
• Se biomarkers:
o Whole blood, hair, nail
o GPX: rapid, good spot def, no contamination; plateau w ↑intake, unstable to storage, lab variation, affected by other nutrient def
• Copper:
o essential nutrient, ↑ demand in infancy (rapid growth)
o adult: 100 mg (95% in plasma)
o highest in liver, kidney, heart
o cofactor: SOD, cytochrome c oxidase (CCO), tyrosinase, monoamino oxidase, lysyloxidase
o infx: to make IL-2 by activated lymphocytes
o CA: plasma CP correlated w dz stage
• CU absorption:
o metallothionein (Cu2+ ions highly insoluble) o Ceruloplasmin: glycoprotein, Cu-dependent ferroxidase, oxidizes Fe2+ to Fe3+ in GI for absorption
• Cu biomarkers:
o Current: Serum Cu, Serum ceruloplasmin (mc)
o Consider: RBC Cu/Zn SOD (severe only), Plt or lymphocyte cytochrome c oxidase
o Future: PAM (peptidylamide monooxygenase), Cu chaperone for SOD
• Chromium picolinate biomarkers:
o None well accepted
o For def: Impaired glucose tolerance
o Plasma not good, levels too close to detection level
o Urine controversial
• Chromium role:
o Regulate glucose metabolism, part of glucose tolerance factor (GTF)
o GTF ↑ insulin effects (↑ binding to cell receptor) → max glucose can enter cells
o regulate plasma lipoprotein
o ↓ serum cholesterol TGs
• Manganese:
o Not a clinical or public health concern
o Plasma levels reflect dietary levels: ↓ w restriction, ↑ w supplements
o High in mitochondria
o cofactor for glycosyltransferases (make oligosaccharides, glycoproteins, proteoglycans)
o for SOD, & metalloenzymes: hydrolases, kinases, decarboxylases, transferases
o Def: ↓ glycoprotein and proteoglycan formation
• Molybdenum:
o For metalloenzymes fxn: xantine, aldehyde, sulfite oxidases
o Biomarkers: ↓urinary sulfate and uric acid
o ↑urinary sulfite, hypoxanthine and xanthine
• MicroNutrient testing:
o Not your average test
o Fxnal test for nutritional status
o Doesn’t measure actual levels, rather the cells use the nutrients
o Up to 6 mo hx of nut status of a person
o Basis: Avg lifespan of lymphocytes and slow change of intracellular nutrient status (6 mo)
• The MicroNutrient test:
o Blood centrifuged and washed ↓48 hrs after draw
o L’s isolated
o Same # L’s incubated in 99 wells, various growth medias, 5 days
o Media: complete, deficient certain nutrient, supplemented
o Add growth mitogen to stim last 4 days
o Day 4 add radioactive label, absorption → amount of growth on last day
o all cells that originally had a def won’t grow on the media w that def
