week 8- micronutrients

Question 1

• trace elements:

Answer 1

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)

Question 2

• First basic law of nutrition:

Answer 2

o No nutrient is absorbed and utilized to the full extent that it is consumed

Question 3

• Bioavailability

Answer 3

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

Question 4

• Important for mineral absorption:

Answer 4

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

Question 5

• Slop ratio method:

Answer 5

o Asses bioavailability
o Ex: measure bodyweight of growing chicks
o ↓ BW will show when nutrients are ↓BA
o Steeper slop means more BA

Question 6

• Balance approach:

Answer 6

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

Question 7

• Absorption/excretion vs retention

Answer 7

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

Question 8

• Why Not Absorption Alone as an index of Bioavailability?

Answer 8

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%)

Question 9

• Functional Response to Mineral Intake

Answer 9

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

Question 10

• Optimal Intake Approach for Assessing Requirement:

Answer 10

o Intake should: optimize physical/mental performance, tx dz, ↑longevity
o Problem: “should duplicate human milk”- too general, Defies population-based approaches

Question 11

• Population/clinical approach:

Answer 11

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)

Question 12

• Traditional Approaches to Determining Mineral Status:

Answer 12

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

Question 13

• Biomarkers; Ex: Body stores of a mineral:

Answer 13

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

Question 14

• Blood/plasma mineral status assessment:

Answer 14

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

Question 15

• Urine, hair mineral stat assess:

Answer 15

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

Question 16

• Functional indices:

Answer 16

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

Question 17

• Iron, from diet to blood:

Answer 17

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

Question 18

• Iron in blood:

Answer 18

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

Question 19

• Daily Fe turnover:

Answer 19

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

Question 20

• IDA:

Answer 20

o	Hypochromic microcytic;
o	Occasional Target cells
o	Pencil shaped poikilocytes
o	↓ reticulocytes
o	Transferrin/TIBC: Normal to High
o	Serum ferritin: ↓ (Very low)

Question 21

• Ferritin plasma, stores, problems:

Answer 21

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

Question 22

• Transferrin saturation:

Answer 22

o	TIBC (total iron binding capacity)
o	UIBC (unsaturated iron binding capacity)
o	33% normal, 47% in AM (after fasting), 13% at night

Question 23

Soluble transferrin receptor conc of plasma

Answer 23

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

Question 24

• Iodine:

Answer 24

o body normally has 20-30 mg, > 75% in thyroid
o rest in mammary gland, gastric mucosa, blood
o main known fxn: thyroid hormone

Question 25

• Iodine balance:

Answer 25

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

Question 26

• Iodine def:

Answer 26

o → goiter (mc F, ↑age)
o Absolute: def (endemic areas)
o Relative: adolescence, pregnancy, lactation
o repletion must be done slowly to prevent hyperthyroidism

Question 27

• Iodine excess and toxicity:

Answer 27

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)

Question 28

• Iodine assess:

Answer 28

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

Question 29

• Thyroid fxn tests:

Answer 29

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)

Question 30

• Iodine skin patch:

Answer 30

o Not reliable form of I absorption

o Oral much better

Question 31

• Zinc, Roles:

Answer 31

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

Question 32

• Zn stores (%):

Answer 32

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

Question 33

• Zinc storage:

Answer 33

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

Question 34

• Zn regulation:

Answer 34

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)

Question 35

• Zn excretion:

Answer 35

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)

Question 36

• Zn def:

Answer 36

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

Question 37

• Other Zn indicators:

Answer 37

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

Question 38

• Selenium:

Answer 38

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

Question 39

• Se biomarkers:

Answer 39

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

Question 40

• Copper:

Answer 40

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

Question 41

• CU absorption:

Answer 41

o	metallothionein (Cu2+ ions highly insoluble)
o	Ceruloplasmin: glycoprotein, Cu-dependent ferroxidase, oxidizes Fe2+ to Fe3+ in GI for absorption

Question 42

• Cu biomarkers:

Answer 42

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

Question 43

• Chromium picolinate biomarkers:

Answer 43

o None well accepted
o For def: Impaired glucose tolerance
o Plasma not good, levels too close to detection level
o Urine controversial

Question 44

• Chromium role:

Answer 44

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

Question 45

• Manganese:

Answer 45

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

Question 46

• Molybdenum:

Answer 46

o For metalloenzymes fxn: xantine, aldehyde, sulfite oxidases
o Biomarkers: ↓urinary sulfate and uric acid
o ↑urinary sulfite, hypoxanthine and xanthine

Question 47

• MicroNutrient testing:

Answer 47

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)

Question 48

• The MicroNutrient test:

Answer 48

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