Magnesium Review

Magnesium Review

DIGESTION AND ABSORPTION

No digestion required
Several influences on absorption

• Enhancement
• Vit D
• Protein
• Carbs
• Fructose
• Oligosaccharides
• Inhibitors
• Phytic acid
• Fiber
• Excessive unabsorbed fatty acids
• Interactions
• Ca
• Ph
• K

ABSORPTION

Active transport

- Brush border transporter (TRPM6)

- Basolateral membrane pumps (ATP-ase pumps)

Paracellular diffusion

- important when intake large

TRANSPORT. STORAGE, EXCRETION

Transported as free Mg, protein bound, or complexed to negative ions (LIKE Ca)

- not regulated, adjusted by intestinal absorption, renal excretion, release from bone

Bone is primary storage

Excretion in urine, feces sweat

FUNCTIONS and MECHANISM

Structural roles in bone, cell membrane, DNA

Important in over 300 enzyme reactions:

• ATP formation and stabilization
• Carbohydrate and fat metabolism
• Protein and nucleic acid synthesis
• Ion transport across cell membranes
• Nerve and muscle function
• Cyclic AMP formation
• Insulin function

DEFICIENCY - 50% Americans deficient

- CAD

- HTN, CVA

ASSESSMENT

- RBC Mg

Ca supplement not balanced by Mg leads to problems with CAD and DM

Phosphorous Review

Phosphorous Review

DIGESTION AND ABSORPTION

Organic food forms are digested

• Hydrolyzed to inorganic phosphate by phosphatases
• Exception: phospholipids in micelles
• Exception: digestion-resistant phytic acid

Absorption typically by passive diffusion

• Active transport available for when intake is low
• Stimulated by vit D
• Absorption inhibitors
• Phytic acid
• Excessive Mg Al Ca

TRANSPORT, STORAGE, EXCRETION

Ph in the blood
- Phospholipids delivered by chylomicrons
- Inorganic and other organic forms absorbed by facilitated diffusion
Cellular uptake passive
- largest amounts in bone and muscle
Excreted in urine
- influenced by diet, vit D, hormones, acid-base balance

FUNCTIONS and MECHANISMS

Bone mineralization
- PTH, calcitriol, calcitonin influence body Ph balance
- PTH impact of kidney is OPPOSITE Ca - Ph is excreted!

Nucleotide / nucleoside phosphatases
- structural roles
- energy storage and transfer
- intracellular second messenger

Phosphorylation in metabolism
- enzyme activation / deactivation
- vitamin activation

Phospholipids
- membrane structure and function

Acid-Base balance
- Ph main intracellular buffer

Oxygen availability
- 2,3 DPG mediates O2 release from Hg

Calcium Review

Calcium Review

Bone density ~ ca supplements
Ca on its own can exacerbate inflammation
Also involved in muscle and nerve function, clotting
cofactors in many reaction

DIGESTION AND ABSORPTION

• Absorption requires soluble free Ca2+
• Adequate stomach acid (watch acid inhibitors)
• Enhancing factors
• Minimal binding factors
• Interactions between Ca
• Enhancing:
• Vit D
• Sugars and sugar alcohols
• Protein
• Inhibiting
• Fiber
• Phytic acid
• Oxalic acid
• Excessive divalent cations (Zn Mg)
• Unabsorbed fatty acids
• Primary system is vitamin D-dependent
• Brush border transporter (TRPV6)
• Cytosolic binding protein (Calbindin D9k)
• Basolateral membrane pumps (ATP-ase pumps)
• Paracellular diffusion between cells -also vit D dependent
• More important when calcium amount is large

CALCIUM TRANSPORT, STORAGE, EXCRETION

Circulates 50% ionized, 50% bound or complexed

Regulated by PTH, calcitriol, calcitonin

Stored in bone, excreted in urine feces sweat

EXCRETION

• Urinary Excretion of Ca
• Enhancers
• Sodium
• Protein
• Caffeine
• Inhibitors
• Phosphorous
• Iron
• Fatty acids

CALCIUM FUNCTIONS AND MECHANISMS

Bone mineralization

• 99% of body Ca found in bone
• Mainly as crystalline compounds such as hydroxyapatite
• Bound to bone proteins such as collagen and to ground substance
• Non-collagen proteins facilitate calcium deposition
• including vit K dependent proteins (osteocalcin)
• Young adult hood = peak bone mass
• Osteoporosis can be due to inflammation not just Ca levels; also vit D, protein decrease

Blood clotting

Nerve transmission

• For NMDA receptors - need Mg in channel -- Ca can rush in unchecked without doorman, Mg. Can cause irritability. 

Muscle contraction

• Ca stored in sarcoplasmic reticulum
• Binds myosin head to contract, requires Ca

Other signaling / regulating functions

• Smooth muscle contraction
• glycogenolysis 
• fatty acid
• glucosenoid formation

Minerals Exam review

Major electrolyes except for which one?

• Cations: Ca Mg Na K
• Anions: Cl-, HCO3-

Major minerals except for which one?

• greater than 100 mg / day requirement
• Cations: Ca Mg Ph Na Cl K
• Anions: 
• Sulfur not included not found independently
• Part of vitamin (thiamine, biotin)
• Sulfur containing amino acids: methionine, cysteine, taurine
• Lipoic acid
• TRACE: 1-100 mg /day
• ULTRATRACE: less than 1 mg / day

Most abundant cations are in body?

• Cations: 
• Na2+ 142 
• K+ 4
• Ca2+ 5
• Mg2+2 
• Anions:  
• Cl- 103 
• HCO3- 28

_____________

CALCIUM

Calcitriol and calcium absorption

• Calcitriol regulates calcium absorption via active transport system
• Involves:
• Ion channel TRPV6 (enhanced by calcitriol and estrogen, expression declines with age)
• Cytosolic binding protein CALBINDIN D9k (enhanced by Calcitriol)

What can improve or block calcium absorption

• Enhance: vit D, protein, sugar
• Inhibit: Fiber, phytic acid, oxalic acid, FAs, Mg and Zn

Review PTH and calcitriol, how it impacts serum Ca

• PTH: increases Serum Ca, Decreases Bone Ca, Increases Intestinal absorption, Increases Renal Reabsorption
• Vit D: Increases Serum Ca, Increases Renal and Intestinal absorption
• Calcitonin: Decreases Serum Ca, Increase Bone, Decreases Renal Reabsorption

Review osteoclasts and blasts

• Osteoblasts
• Bone building ~ calcitonin
• Osteoclasts
• Bone degrading ~ PTH

Bone density, when does peak bone mass occur, what life cycle? early adulthood

Binding proteins that regulate Ca dependent enzymes

• Blood clotting
• Muscle contraction
• Calmodulin:
  
  
  • a cytosolic calcium-binding protein in most cells
  • calcium binds and changes its confirmation shape to stimulate a variety of enzymes
  • Calcinuerin
  • Myosin light chain kinase
  • Phosphorylase kinase
  • Calcium calmodulin kinase

What is the optimum levels are the generate health outcome, what doses do not?

• 1,000 mg daily
• 1,200 mg daily for over 70
• TUL 2,500 mg 

Calcium interactions:

• >3:1 Ca:Ph inhibits Ph absorption
• 800mg+ Ca decreases Fe absorption
• Ca diminishes absorption of FAs
• Magnesium OPPOSES Calcium

________________________________

Minerals involved in hydroxyapetite

• Ca
• Mg
• Ph
• Manganese

What mineral is most likely to be deficit in diet, least likely?

• Most likely: Mg
• Least likely: Na

________________

Phosphorous


__________________

Magnesium

What mineral in certain color vegetables? - green leafy vegetables

Ca function with NMDA receptor, how does Mg gatekeeper this and neuroexcitability?

Magnesium function

• BONE MINERALIZATION
• Enzyme reactions ~ 300s
• Glucose, fat, protein, vitamin, nucleic acid
• Primary function with ATP synthesis
• Other
• Blood clotting
• Ion channel regulation
• Antagonism of IC Ca
• smooth muscle relaxation
• effect on blood vessels and blood pressure
• deficiency ~ effect on heart
• too much, effect on smooth muscle and colon
• what effect does Mg levels have on K (hypokalemia, hyperK)

Which minerals involved with ATP, Krebs cycle, B-oxidation, glycolysis?

• Magnesium

Relationship between Ca and Mg for muscles contraction

• After cell stimulation, Mg inhibits Ca release from sarcoplasma and enhances Ca uptake into sarcoplasm
• Mg decreases Ca flux across membrane
• Competes with Ca for binding sites
• Overall inhibits contraction

Magnesium toxicity and deficiency of Mg

• Deficiency
• Low K
• NM excitability
• Chronic: HTN, arrhythmia, CV disease, Diabetes, migraine
• Toxicity
• Loss of reflexes
• Hypotension, apnea, EKG changes
• Muscle paralysis, respiratory failure

____________________

Osteoporosis - understand vit C role in protecting bone health and vit K

_____________________

Water

What % of body is water?

• 60%

% blood volume circulated through kidneys?

• 20%

% of GFR that is excreted as urine (few % questions)

• Of the 185 L filtrate formed daily, 1.5 L excreted as urine
• 1% excreted as urine

Review components of the nephrons - aff and eff arteriote, glomerulus, prox convulted tubules, loop henles, loops, collecting ducts; PCT LOH DCT CD

• Tubular
• Bowman's capsule (capillary network)
• Proximal convoluted tubule
• Loop of Henle
• Distal convoluted tubule
• Collecting Duct
• Vascular
• Glomerulus
• 20% of plasma entering glomerulus is filtered
• Glomerular filtration rate is 130 mL/minute
• Efferent arteriole - out
• Afferent arteriole - in

Know where most Na is reabsorbed, most water reabsorbed

• 90% of Na, Cl-, K+, glucose, AAs, bicarb, Ph, water resorbed in PCT
• Reabsorption also happens at LoH, DCT, and CD
• 20% water in DCT and CD

Understand hypothalamus and kidney in regulated extracellular osmolarity and volume

• Increase in ECF osmolarity (dehydration) causes hypothalamus to release vasopressin

Hormones - ADH, Aldosterone (mineral corticoid - how to differentiate with glucocorticoid), ANP (Na)

• Vasopressin (ADH)
• Controls osmolarity 280-295 mOsm/L
• Release is stimulated by:
• Hypothalamus, left atrium - detect increased ECF osmolarity increases
• Angiotensin 2
• Effects:
• Reabsorption of water (distal tubule and collecting ducts)
• Stimulation of thirst
• Vasoconstriction of arterioles
• RAA
• Control Na balance
• Activation when JXG apparatus detects low BP and low ECF (dehydration)
• RENIN secreted by JXG (innervated by sympathetic NS)
• Renin hydrolyzes Angiotensin (then in lungs by ACE) to Angiotensin 2
• Angiotensin effects
• Vasoconstrictor
• Thirst
• Stimulates vasopressin
• Reduces GFR
• Stimulates adrenal cortex to release Aldosterone
• Aldosterone
• Release due to 
• Angiotensin
• low natiuretic peptides
• Increase K and low Na
• Effect:
• Reabsorption of Na and excretion of K
• Water reabsorption follows Na and Cl
• ANP
• Stimulated by atria of heart when BP elevated
• Effect:
• Increases GFR: Natiuresis and Diuresis
• Low BP
• Dilates BVs

______________

SODIUM

Which mineral related to HTN and which to lower BP?

• Na HTN
• Mg lower BP

If something is low Na, what does that mean or indicate?

• High in water, low Na concentration

What minerals can you lose when exercise vigorously, esp at high temp

• Na

What is major ECF cation?

• Na2+

________

Potassium

ECF concentrations regulated through hormonal and renal functions

• Large rise in plasma K countered by insulin which promotes uptake into muscle and liver
• Also increased renal excretion of K

___________

Chloride

What most abundant anion is in the ECF?

• Cl-

Major function of Cl-?

• Gastric HCl

pH and minerals that can regulate body fluid pH

• As blood pH increases, protein bound calcium increases and ionized calcium decreases
• Increase of 1g/dL albumin ~ decrease 0.8 mg/dL total serum calcium
• Ph is a buffer within cells
• Water: H20 + CO2 = H2CO3 = HCO3= + H+
• K+
• Protein
• Hemoglobin

When you say acid and base balance what is referring to?

• H+ concentration

Acidosis - what does it mean? Aklaosis?

• Low pH
• High pH

What happens to pH when hyperventilating or blowing off CO2?

• Hyperventilating = blowing off acid = respiratory alkalosis, rise in pH

Current research on mineral and foods associated with reduction in systolic and diastolic BP?

• Na
• K

What is it important to provide body with to prevent body loss of sweating or dehydration in marathon runners?

• Na

ch 13:
_______________

IRON

• DIGESTION, ABSORPTION, TRANSPORT
• DIGESTIONS
• Heme - proteases release from globin, not effected by enhancer and inhibitors
• Nonheme - HCl and proteases released from food
• Enhancers: Sugars, Acid, Mucin, Meat, fish, poultry
• Act as reducing agents to Fe2+ or as chelators or ligands that help with absorption; Fe3+ converted by HCl into absorbable Fe2+ (reduced state)
• Inhibitors: Alkaline, Polyphenols, Oxalic acid, Phytic acid, Divalent cations
• Act as chelators tightly making it less soluble
• ABSORPTION
• Heme - 
• Absorbed intact by carrier protein
• Degraded in enterocyte to separate iron
• Non-heme
• Reductases reduce Ferric iron
• Ferrous iron absorbed via DMT1 transporter

What micro mineral essential for brain function?
Fe

What is iron content in Western Diet?

• Heme 
• Animal
• Non heme
• Plant - grains, legumes

What can enhance uptake of non heme iron and inhibit?

• see above

Hemosiderin -

• Degradation product of Ferritin

Ferritin 

•  storage form

Hepcidin

• Copper containing enzyme
• Near ferroprotein (tranport out of cell)
• Stimulated:
• Increased transferrin saturation 
• Inflammation ~ AOCD
• Inhibited
• Hypoxia ~ EPO

Fe def anemia -

• whose at risk
• infants . young children
• Adolescents
• Pregnant
• Renals
• GIB
• Malabsorption
• Vegetarians

Fe Toxicity

• Hemachromatosis

Fe participates in ETC by cyotchrome

________________

ZINC

Sources of Zn

• Complexed with nucleic acid and AAs
• Organs and seafood

Taste perception - what is involved?

Relationship between Zn and vit A

• Zn deficiency related to low retinol mobilization from liver

How does Cu impact Zn absorption?

• Excessive Zn increases metallothienen binding of Cu in intestines

Cu-Zn SOD

• Which in cytoplasm and which in mitochondria
• See below

How are phytates involved with absorption of Ca and Zn?

• Inhibitors

Zn absorption

• Enhancement ~ GAP
• Acidic, Glutathione, Protein
• Inhibition ~ POP D
• Phytates
• Oxalic acid
• Polyphenols ~ tea/coffee
• Fe Ca 

Relationship between Fe and Zn in terms of absorption

• Zn can inhibit NONHEME FE absorption

Pnuemonic: POP-D Phytates Oxalic Polyphenols Divalent

Zn Storage

• Metallothionein ~ short term storage protein in all body tissues

Zn functions:

1. Heme synthesis
2. SOD
3. Zinc Fingers/ DNA
4. Wound repair / Colds / Eye health

______________________

COPPER:

Copper sources:

• Meats
• Shellfish

Absorption

• Enhanced: ~ GAP
• Acid , Glutathione, Protein (histidine, cysteine)
• Inhibited: POP D
• Phytates
• Zinc (stimulates metallothionein synthesis ~ binds copper)
• Accumulation of Cu in intestinal cells ~ Menke's disease

Storage:

• Liver > muscles as metallopthionein
• Cu used for ceruloplasmin synthesis

• Mobilizes stored iron (ferritin)

Copper function in relationship to oxidizing iron, bound to transferrin

• Ceruloplasmin:
• AKA ferroxidase
• Critical for iron use
• Found in blood and membranes where is oxidizes FERROUS Fe3+ and Mn2+
• Oxidization of Fe3+ to Fe2+ critical for cellular iron release and binding to TRANSFERRIN for transport to body tissues
• Absence of ceruloplasmin impairs Fe use and increased iron deposition occurs in liver, pancreas, brain with low serum Fe levels
• Also an acute phase reactant
• Hephaestin
• Like ceruloplasmin, oxidizes Fe
• Located on enterocytes (basolateral membrane)

Why does iron bind to proteins?

• Very pro-oxidant, to protect tissues

what minerals and vitamins involved with heme synthesis?

• one of vitamins is a water soluble vitamin
• Fe
• Zinc

Go over ETC and go over electrons and what minerals involved?

• Cytochrome c oxidase
• 3 Cu atoms
• Receive electrons from cyt c ox and transfer 
• Terminal step in ETC - O2 reduced to H2
• Fe

Hgb and HCT as assessment of Fe

• 
  

What minerals and trace minerals involved with greatest number of enzyme systems

• Mg

What vitamin(s) can enhance Copper reduction?

• Cu2+ is reduced by superoxide radical and SOD

What dietary types of food component can impede with Cu absorption?

• see above

Cerulosplasmin function

• see above

What minerals can cause damage to cells when in free Fe forms?

• 
  

Wilson, Hemochromatosis, Heshan's disease

• Wilson see below
• HC - Fe, see above
• Heshan's - 

Selenium, glutathione and glut oxidase

• see below

Antioxidant defense systems, SOD, SOD-Mg SOD-Cu, what organelle will you find them

• SOD is a Cu and Zn dependant enzyme (in mitochondria it is Mn dependent)

Genetic disease

• Wilson's
• defective biliary copper excretion
• Eye finding - Kayser Fleischer rings

Organs affected by excessive  Cu?

• Liver

Cu and neurotransmitters:

• Catecholamines
• Skin Pigment
• Vitamin C reduces Cu in DA to NEPI
• Albinism

Cu Deficiency

• Hypochromatic microcytic anemia
• Leukopenia
• Depigmented hair and skin
• Found in excessive ZINC ingestion

_______

Selenium

Think thyroid and glutathione

Why is soil important related to Se?

• Variable in soil so plant content variable
• Organ meats the best

Digestion / Absorption

• Selenomethionine best absorbed
• No regulation
• Enhanced: vit A, C, E, glutathione (reduced)
• Inhibited: heavy metals (mercury), Phytic acid

Transport / Metabolism / Storage / Excretion

• AA transporter
• Liver uptake, Incorporated into SELENOPROTEIN P
• Plasma selenium is in SELENOPROTEIN P
• Storage: thyroid, kidney, liver, heart, pancreas, muscle
• Excesses excreted through kidneys

MOA:

• Thyroid hormone metabolism (IODOTHYRONINE 5'DEIODINASES)

• Antioxidants: 
• glutathione peroxidase - removes inorganic and organic peroxides
• thioredoxin reductase
• selenoproatin P - removes peroxynitrite
• Capillary endothelial cells
• Peroxynitrite (ONOO) made by WBC from superoxide radicals and nitrogen oxide NO  - can cause DNA damage
• methionine R sulfoxide reductase

Se Toxicity

• Selenosis ~ miners
• impact on hair, nails (brittle)

Link between Se and glutathione

• Integral part of the glutathione peroxidase enzyme
• Cytosol > mitochondria
• Catalyzes the removal of hydrogen peroxide (H2O2) and organic peroxides

Se Deficiency:

• Hypothyroidism

Food high in Se

• Organ meats

What minerals involved with thyroid hormones

• Se
• I

_______________

CHROMIUM

Think insulin, blood sugar, glucose
In food, Cr3+ in Trivalent form
highly toxin, human carcinogen, CR6 and CR3

Digestion and absorption

• Gastric acid facilitates release
• enhances: ~GAP + vit C
• AAs, picolinate, vit C
• inhibits: POP D
• Phytates

Transport / Storage / Excretion

• Transferrin in blood
• Stored with FERRIC FE, stores decline with aging
• Urine excretion

MOA

• Potentiates action of insulin
• binds with chromodulin to stimulate increased insulin receptor activity and glucose uptake

What mineral involved with glucose tolerance and insulin function?

• Chromium

Chromium - insulin receptors, glucose uptake, high carb diet effect

• related to Chromodulin

Chromium picolinate -

• Large consumption leads to chromosomal and organ (renal and liver) damage

__________________

Function Function Function

Fe metabolism, connective tissue formation, ceruloplasmin, and cytochrome c oxidase

• what mineral are we talking about? Zn, I, Mg, Manganese, Cu

Tissue growth and repair, antioxidant, gene expression ?

• Cu, I, Zn, Mg

Thyroid hormones structure:

• Zn Mg I Magnanese

ATP formation, bone, ion transport

• Mg Manganese I

Antioxidant function, collagen synthesis and urea and glycocaminoginoglcans

• I, Mg, Manganese

_____________

IODINE

Think thyroid hormone T4 and T3
Se converts T4 to T3
Source: seafood for I

Absorption, Transport, Excretion

• AA bound to iodine requires digestion
• Oxidized forms reduced to iodine by glutathione
• Free I in blood, trapped by thyroid
• Excreted in urine

MOA

• Synthesis of thyroid hormones
• Transport of thyroid hormones in blood
• Thyroxine binding globulin
• Albumin
• Transthyretin
• Metabolism of T4 (T4:T3 13:1; T3 5x more potent than T4)
• Requires selenium dependent deiodinase

Review goiter

• Less than 10-20 ug / day of idoine
• Enlargement of thyroid
• Overstim of TSH

cretinism

• I deficiency in fetus due to I def in mother
• MR, hearing loss, motor dysfunction

Causes of hypothyroidism:

• Vitamin A reduces I uptake in thyroid gland
• Heme iron is a component of thyroperoxidase
• Selenium converts T4 to T3

Goitrogens:

• Augment TSH release causing thyroid enlargement
• Types:
• Cabbage
• Cassava
• Lithium

________________

Manganese: (MAGIC)

SOURCES: low carb sources
- vegetarian diets higher in manganese
- wheat germ

Digestion /Absorption

• DMT1 or ZIP14 transporters
• + Protein 
• Histidine, Citrate
• - ~ POP D
• FIber, Phytate, Oxalate, Fe, Cu

Transport / Storage / Excretion

• Liver
• Free or bound to proteins/transferrin
• ZIP or DMT uptake > transferrin receptors
• Stored: mitochondria, hydroxyapetite

MOA:

• Metalloenzymes
• Bone & cartilage ~ glycosaminoglycan
• Cofactor in chondroiton sulfate
• Urea synthesis ~ arginase
• GLUCONEOGENESIS - proper dispensation and protein and amino acids
• Antioxidant ~ Direct scavenger of peroxyl radicals
• Manganese SOD in mitochondria
• Copper-Zinc SOD in cell cytosol
• TOXICITY ~ miners, parkinsonism

Trace minerals, know key enzyme in gluconeogenesis

• Biotin
• Manganese

___________________

Melibdinum 

Go over melibdinum function

Digestion /Absorption / Transport / Storage / Excretion

• Competes with sulfate
• Travel in blood as MOLYBDATE bound to transporters
• Stored: liver, kidney, bone (very little stored)
• Urine

MOA

• MOLYBDOPTERIN !!!! key
• Facilitates oxidation reduction reactions
• 4 essential enzymes:
• Sulfite oxidase (sulfite to sulfate)
• Aldehyde oxidase (metabolism of aldehydes)
• Xanthine dehydrogenase & xanthine oxidase
• Nucleotide metabolism
• Uric acid formation ~ gout
• Amidoxime reductase
• Drug metabolism, detoxification

 know what gout is

• With high Mo (TUL 2 mg), high uric acid forms and can cause gout

familiar with xanthene oxidase

• Xanthine oxidase is a form of xanthine oxidoreductase, made when conformational changes occur in the original enzyme. 
• Both forms of the enzyme catalyze the conversion of hypoxanthine to xanthine and xanthine to uric acid as a part of the purine degradation pathway. 
• This is pertinent both for the proper elimination of excess purines, but also for excess xanthine. 
• Increased xanthine elimination via the kidneys can cause renal calculi to form. 
• Xanthine oxidase can be damaging to the body as it produces large amounts of hydrogen peroxide.

Sulfite oxidase

• an enzyme necessary for the final step in the conversion of methionine and cysteine. 
• This step converts sulfite to sulfate where sulfate is then excreted in the urine or used for synthesis of other sulfur-containing compounds.
• One effect of decreased sulfite oxidase activity has severe neurological effects. 
• Isolated sulfite oxidase deficiency is typically diagnosed in infancy and may produce neurological symptoms including encephalopathy, difficulty feeding, spastic quadriplegia, arching of the spine, or microcephaly.

know nutrient diet interaction of diuretics

• Thiazides increase Zn urine excretion
• Mg and K depleted

nutrient diet interaction of GERD

ch 14

_________________

Fluoride 

What can inhibit fluoride absorption?

• Ca and Mg

which micro minerals can contribute to hydroxyapetite crystals and more resistant to acid erosion?

• F

_________________

Arsenic

4-5 questions on arsenic

know arsenic function in metabolism of methionine to taurine

• SAM function may be diminished by As deficiency
• Meth catabolism produces SAMe which provides methyl group needed for arsenic methylation in liver
• Methylation decreases As accumulation in liver
• Taurine?

know arsenic related to SAMe

• See above

know arsenic relation to iodine uptake

• 
  

black foot disease

• peripheral vascular condition leading to gangrene with As intoxication

_______________

Boron

what ultratrace element deemed dangerous in 1920s and then essential in 1980s?

• B

Sources: found, what food

• Plants, fruits, nuts, legumes
• Wine, cider, beer

functions

• esp cell membrane stability
• inflammatory response
• bone development
• mediation of inflammatory events
• glucose metabolism

_______________

Nickle

What mineral can influence Nickle absorption?

• Competes with Fe for absorption
• Ni absorption increases with Fe deficiency

What elements most abundant on Earth?

• Fe 4th most

Which element can impact collagen synthesis and bone mineralization?

• 
  

signs of deficiency and toxicity

• Allergic reactions on skin
• DNA damage

______________

Silicon

What can inhibit silicon absorption, which foods are rich in silicon?

• Plant
• Seafood
• Inhibitors: fiber, cations, alkaline

Be familiar with silicon toxicity over long terms

• Kidney stones, related to long term antacid use
• Asbestos - silicosis

______________

Vanadium

What are some sources of vanadium?

• Shellfish

3-4 questions on vanadium:

• Na K pump
• competes with other metals for ATP sites and inhibits passage of molecules
• Can cause weakness in muscles for instance
• tox
• Green tongue syndrome
• Miners
• def
• none

__________

Cobalt

Cobalt - relationship with B12

• usually found with B12 in foods

Copper and Zinc Review

ZINC

Insulin
SOD
Cognitive function
Male sex health
Oysters - aphrodisiac - very high zn content
Beef pork
Seeds




DIGESTION, ABSORPTION, TRANSPORT

Similar to NON-heme iron

Digestion:

• HCl
• Proteases & Nucleases release from food

Absorption:

• Carrier (ZIP4) mediated process of low-moderate intake
• Passive paracellular diffusion with high intake
• Affected by enhancers and inhibitrs
• Enhancers:
• Organic acids
• Glutathione
• Amino acids
• low pH
• Inhibitors:
• Phytic acid
• Oxalic acid
• Selectred nutritients
• Iron
• Calcium
• High pH

Availability from meat better than vegetables

ZINC in the ENTEROCYTE
Used for gut cell functions
Temporary storage may be excreted

• Metallothionein is primary  storage protein

Transported into circulation by ZnT1
Albumin is primary blood carrier protein

ZINC STORAGE and EXCRETION
Storage:

• Found in all tissues esp liver, kidney, muscles, skin, bones
• Mostly in functional and structural proteins
• Liver can respond to low zinc status by releasing zinc
• Metallothionein is primary storage protein
• Also bind other mineral and has antioxidant activity

Excretion

• Mainly in GIT
• Unabsorbed zinc
• Sloughed intestinal cells
• Secreted zinc proteins
• Carrier based transport
• Small amounts via kidney and skin

FUNCTIONS and MOA
Numerous enzyme roles

• Structural integrity of enzyme
• Catalytic activity of enzyme

Gene Expression

• Zn finger structures in transcription factors
• Zn binds to portions of transcription factors proteins
• Resulting shape allows binding to regulatory region of gene
• May also participate in regulation of RNA translation

Structure and function of cellular membranes

Other roles

• Acid base balance
• CARBONIC ANHYDRASE
• Vitamin A and alcohol metabolism
• Retinol to retinal
• Protein digestion
• Antioxidant defence
• SOD (also copper)
• Folate digestion
• Wound repair
• Immune function
• Cell mediated and humoral immunity
• Cytokine production and thymulin activity
• Cell replication and growth
• Nucleic acid metabolism
• Protein synthesis
• Gene expression regulation
• Taste function ~ gustin
• Carbohydrate metabolism
• Pancreatic insulin storage
• Insulin response pathway

INTERACTIONS
Copper
Iron

DEFICIENCY


COPPER

Cu3+
Cu2+

DIGESTION and ABSORPTION

Gastric HCl and enzymes required

Reduction to Cu1+ required
Transporters Ctr1 and DMT 1
Affected by enhancer and inhibitors

• Enhancers
• Some amino acids
• low pH
• Glutathione
• Acids
• Inhibitors
• high pH
• Phytic acids

In the enterocytes

• Chaperones bind copper and deliver it to targets
• Enzymes for functional uses
• Metallothionein for temporary storage
• High zn intake causes increased copper loses
• ATPase 7A for entry into blood
• Ceruloplasmin formed in liver is primary carrier
• Menke's disease

Storage

• Liver is primary storage organ
• Metallothionine is primary storage organ

Excretion

• Mainly via secretion into bile
• Small amounts via kidney and skin

FUNCTIONs and MOA

• Ceruloplasmin
• Fe2+ oxidation for transport
• Antioxidant
• SOD
• Energy production
• Cytochrome oxidase ATP production
• Amine oxidases
• Catabolism of histamine neurotransmitters
• Connective tissue stabilization
• Collagen and elstin cross-linking
• Tyrosine metabolism
• NEPI synthesis
• Melanin production
• Pro-oxidant when unbound
• Wilson Disease
• Immune function
• Gene expression

Iron Review

Iron

SOURCES
Heme Iron

• Meat, poultry, fish

Non-Heme Iron

• Plants
• Dairy
• Influenced by enhancers and inhibitors
• Vit C enhances
• Phytates inhibit
• Polyphenols - fruits, veg, soy, coffee, tea

DIGESTION, ABSORPTION, TRANSPORT, STORAGE

Heme iron digestion:

• Proteases released from globin
• Not affected by enhancers / inhibitors

NON-Heme iron digestion:

• HCl and proteases released from food
• Affected by enhancers / inhibitors
• Enhancers
• Sugars
• Acids and acidic pH
• Mucin
• Meat & fish
• Poultry
• Inhibitors
• Alkaline pH
• Polyphenols (coffee)
• Oxalic acids (spinach, tea)
• Phytic acids (whole grains, legumes)
• Phosvitin
• Divalent cations\
• MEDICATIONS

Heme-Iron Absorption

• Absorbed intact by carrier protein (Heme Carrier Protein 1)
• Degraded in enterocyte to separate iron

NON-heme Iron Absorption

• Reductases reduce ferric iron Fe3+
• Ferrous iron Fe2+ absorbed via DMT1 transporter

Iron in the Enterocyte:

• Used for gut cell functions
• Transported into circulation
• Requires oxidation in Fe3+ state
• Requires hephaestin and ferroportin
• Hepcidin controls ferroportin
• Hepcidin made in liver 
• High iron levels trigger more Hepcidin and leads to less Iron in circulation
• Low iron levels trigger less Hepcidin and more Iron in circulation
• Stored, may be excreted
• Stored in ferritin
• Cells live 2-3 days
• Transferrin transport
• Carries iron absorbed from gut (protects body from oxidizing potential of iron)
• Carries recycled iron
• Carrier iron released from storage
• Cell membrane uptake via transferrin receptors
• Stored in liver bone marrow spleen
• Primarily as ferritin
• Hemosiderin used when iron high

TURNOVER EXCRETION

Iron is recycled extensively

• Reticuloendothelial cells take up old RBCs
• Haptoglobin and hemopexin clean up iron from hemolyzed RBCs
• Excretion via:
• Intestines
• Skin
• Kidneys
• Menses

FUNCTIONS
Oxygen transport

• Hemoglobin - 2/3rd of total body iron
• Myoglobin - capillary blood to myocytes

ETC

• Cytochromes
• moves protons
• Other enzymes
• Iron bond to sulfur

• Mono-oxygenases & Di-oxygenases
• Amino acid metabolism
• Synthesis of neurotransitters, carnitine, collagen
• Peroxidases
• Antioxidant role ~ catalase
• Immune defense
• Thyroid hormone synthesis ~ peroxidase

INTERACTIONS

• Do not take iron with calcium and zinc supplements

DEFICINIENCY

• At risk
• new borns
• Menses
• Malabsorption
• Antacids
• Vegetarian

TOXICITY

Hemochromatosis

• Genetic
• Nongenetic