Micronutrients/Minerals Interactons

Question 1

B-VITAMINS-WHAT ARE THEY FOR?

Answer 1

*Nutrients involved with TCA: b-vitamins (esp b1/Thiamin, b2/FAD, b3/NAD, b5/CoA, Iron, Mn, Mg)
b vitamins are found mostly in fortified foods
*Req’ b1, b2, b3, b5, alpha lipoic acid
Pyruvate dehydrogenase (glycolysis)
A-ketoglutarate dehydrogenase (TCA)
BCKA dehydrogenase
*ATP = Adenosine Triphosphate; example of an essential non-vitamin coenzyme; Most widely distributed coenzyme in the body.

Question 2

b1/Thiamin:

Answer 2

Decarboxylation/Dehydrogenase rxn’s (transfer 2-C units)
Pyruvate dehydrogenase (def = lactic acidosis)
BCAA dehydrogenase (def = MSUD)
A-ketoglutarate dehydrogenase ( def = alzheimer’s, Parkinson’s, Huntington’s)

PPP: Transketolase (Glucose > Glucose-6-P via transketolase) yielding R5P and NADPH
*R5P = needed for synthesis of Nucleic acids/sugar molecules
*NDPH = Provides H atom for chem rxn, results in production of steroids, FA, AA< Neurotransmitters, etc

Req Magnesium to be converted to biologically active form (Thiamin Diphosphate, TPP)
correcting b1 deficiency is not possible without correcting co-deficient magnesium

B1 regulates sodium channels
Large amounts of Coffee + Tea (anti-thiamin factors; Tannins)

Inhibited by: RAW freshwater Seafood/Fish, Tannins, Sunlight/Radiation, Sulfite/Nitrates, Cooking

Enhanced by: other b vitamins (except b6), Choline, Copper, Molybdenum, Allicin (onion/garlic)
Diuretics, Anticonvulsants

B1 Def: Contributes to ATAXIA (loss of ankle knee reflex, gait abnormality, speech changes, along with E, B12), 
 Neuropathy, Alcohol (Wernicke-korsakoff’s syndrome = alcohol dementia), Wet B - Heart (think: blood), Dry B - Nerves, Lactic acidosis, BCKA
Food sources: meat, whole grains, nuts, seeds, wheat germ, egg yolks, squash, b. yeast

Question 3

b2/FAD:

Answer 3

Energy metabolism (precursor of FAD for ETC, ATP, FA synthesis)
- Dehydrogenase: Pyruvate Dehydrogenase, a-Ketoglutarate dehydrogenase, BCKA dehydrogenase, succinate dehydrogenase
- REDOX rxn, oxidation of AA/FA
Fatty Acyl-Coa dehydrogenase
Retinal dehydrogenase

Methylenetetrahydrofolate Reductase
FAD req cofactor for folate-metabolizing enzyme, MTHFR

Xanthine Oxidase converts Purine > Uric acid
Aldehyde Dehydrogenase
Hydroxylation rx of hepatic drug detox
FMN as cofactor - Pyridoxal phosphate (b6)
B2 helps B6 (activates B6) convert Tryptophan to B3
Pyridoxine 5’ Phosphate oxidase
Glutathione Reductase = FAD dep
Oxidation pathway converts O2 > H2O2
Magnesium + Manganese activate B2

Inhibitors: Antimalarial, High dose BCP may cause b2 insufficiency, High dose Antidepressants (Tricyclics), Synthetic Thyroid rx

B2 Def: Fissures of Nasal Sebaceous glands (Nasolabial Dyssebacia), Ariboflavinosis/Cheilosis/Glossitis (Cracked Mouth, tongue swelling)
Polyps in Nose = Salicylate sensitivity
Paresthesias of lips/tongue/fingers = Calcium deficiency
B2 Food Sources: Enriched wheat/grains, milk, eggs, Meat, Legumes

Question 4

b3/NAD/niacin:

Answer 4

Redox (reduction-Oxidation) rxn

Energy metabolism, Precursor NAD, NADH+
CHO metabolism (Glycolysis, PPP)

Malate dehydrogenase - NAD dep
Catalyzes malate > oxaloacetate in gluconeogenesis
Can be synthesized from Tryptophan (with support from Iron, B6, B2)

DNA/Purine biosynthesis

NADP involved in regulating Glutathione, Vitamin C
Helps to lower Phosphate levels in end-stage renal disease (CKD)
Niacin interferes w/ the sodium-phosphate pump & causes decreased transport of Phosphate

Cardiovascular (used to treat elevated cholesterol/interacts w/ statins)

Synthetic Form = Nicotinic Acid

Bioactive Natural Form (in foods): Nicotinamide Adenine Dinucleotide (NAD)

B3 toxicity: Flush/redness

B3 Def: Fissuring of Tongue, Pellagra (Dementia, Diarrhea, Dermatitis, Death), Hives/rash, Hyperpigmentation (also b9/b12)

Question 5

b5/coa/Pantothenic acid:

Answer 5

metabolic pathways

Coenzyme A aids in transfer of FA from cytoplasm > mitochondria
Fatty Acids are catabolized to Acetyl CoA via b-oxidation inside mitochondria
Fatty Acids are synthesized from Acetyl CoA in cytosol (outside mitochondria)

Question 6

b7/biotin:

Answer 6

Carboxylase
1st step of Gluconeogenesis: 3-or/4 c-molecules such as Pyruvate > Pyruvate carboxylase > glucose (req b7 for activity)

Histone modification, cell signaling

Genetic expression–transcription of some genes for translation of mRNA and cell signaling

Works with Chromium as insulin receptor binding factor
Inhibited by Avidin in Eggs

Def: Alopecia, Scaly red rash around eyes, nose, mouth & genital area *Neurological sx may show with biotin def

Question 7

*B5 & B7 share similar structures & compete for uptake
*B5 & B7 depleted by anticonvulsants, sulfa drugs
*See Warning on labels: supplemental biotin gives trouble interpreting labs**

Question 8

b6/pyridoxine/PLP/Pyridoxal-5-Phosphate <(active):

Answer 8

Transamination (the transfer of amine group to synthesize AA acids, such as a-keto acid for gluconeogenesis)
Morning Sickness, Hyperhomocystenemia, carpal tunnel, PMS, depression, pyridoxine dependent epilepsy
cheilosis/inflammation of mucous membranes of lips (also b2, b3)

Glycogen Phosphorylase (rate limiting enzyme; Needs B6, – Phosphoglucomutase (PGM)…converts G1P > G6P, Debranching enzymes
B6 needed by Glycogen Phosphorylase to shorten chain

Decarboxylation (the removal of COO= from AA or other compounds, such as Glutamate > GABA)

Neurotransmitter synthesis, AA & protein metabolism
B6 req for Glycogen phosphorylase (enzyme catabolizing glycogen to Glucose-1P)

X-linked Sideroblastic anemia —- (lack ALA synthase which req’ b6)

Heme Synthesis: b6 is coenzyme for the 1st step in Heme Synthesis for ALA-Synthase enzyme (Succinyl CoA + Glycine > 5-ALA)
Transulfhydration: Remethylation of THF after MTHF form is used to methylate Homocysteine (generating THF and Methionine)
B6 decreases effects of Anticonvulsants
Has effects on very uncommon drugs (TB, Penicillamine, Epileptic, Corticosteroids)

⭐ Adequate b6 decreases the need for b3/niacin (b/c b6 is req’ for synthesis of b3/niacin FROM Tryptophan also B2, Iron), B6 needs Riboflavin (b2) to be activated
Elevated Xanthurenic acid
B6 Inhibits biosynthesis of b1
B6 Inhibitors: MAO-inhibitors, Antituberculars (inhibit enzyme action req’ b6), Leucine (antagonizes b6 functions converting tryptophan > b3), Penicillamine, 
 Epileptic drugs, Alcohol (increases P5P catabolism), Milling/processing, Fiber, Contraceptives, Dyes
B6 def: dermatitis, brain wave abnormalities, cheilosis, glossitis (but also b2, b3), seborrheic rash, fatigue, neuro (confusion, seizures, convulsions)
B6 Tox: sensory neuropathy, ataxia, degeneration of neurons, extremity tingling/tendon reflexes, impaired motor control, degen of spinal cord, peripheral nerves, 
 painful/disfiguring dermatological lesions, photosensitivity, GI sx (nausea/heartburn)
large intakes may enhance immune function, ameliorate sx of PMS, carpal tunnel/asthma, morning sickness, high homocysteine
b6/P5P Food Sources: Chicken, Liver, eggs, Chickpeas, yeast, Nuts

Question 9

b9/Folate:

Answer 9

Transfer of 1-C unit
Primarily absorbed in Jejunum
Masks b12 deficiency (in the situation of Anemia….cannot decipher where anemia is coming from)
NSAIDS (large doses impact folate)
Anticonvulsants (impairs bioavailability of folate)
Methotrexate (folate antagonist)
BCP (high dose estrogen)
Folate Def in elderl results from poor diet or use of drugs that impede folate absorption (antacids raise pH)

Question 10

b12/Cobalamin:

Answer 10

Cofactor for Methionine synthesis
Methionine Synthase (b12 dep), catalyses conversion of 5-MTH and Homocysteine to Tetrahydrofolate/L-methionine
megaloblastic/macrocytic anemia (pernicious autoimmune disease anemia likely from lack of Intrinsic Factor)
b12 Def: Contributes to ATAXIA – loss of ankle knee reflex, gait abnormality, speech changes (along with E, B1), Premature graying (also Cu), Hearing Loss
Undetected b12 def for several years = Neuropsychiatric damage that may be irreversible
Common causes of b12 def: Gastritis, HIV, renal disease **Hypothyroidism iS NOT a common cause of b12 deficiency

Question 11


Choline:

Answer 11

Phospholipid
Needed to produce Acetylcholine (neurotransmitter for memory, mood, muscle control, brian/nervus)
Acetylcholine: increase motility, relax sphincters, stimulate secretions
Needed by all plant + animal cells to preserve structural integrity
Important role in modulating gene expression
cell membrane signaling (Choline needed to synthesize Phosphatidylcholine + Sphingomyelin)
lipid transport/metabolism
Early brain development
NOT involved in bones & teeth (only Mg, P, ca)

Def: associated w/ metabolic syndrome, NAFLD (def contributes to fat buildup in Liver), Muscle damage

Question 12

Alpha Lipoic Acid (oxidized form)/Thioctic Acid

Answer 12

Synthesized by fat/water soluble antioxidants
Functions as antioxidant in reduced & oxidized forms
Cofactor for mitochondrial enzymes
Regulates other antioxidants (e, c, CoQ10, Glutathione)
Chelates metals (mercury, cadmium, arsenic)
Inhibits Copper and iron induced oxidative damage (hydroxyl radicals)
Increases insulin signaling cascade, increases GLUT4
Activates protein kinase b (glucose metabolism, transcription, etc)

Toxicity: dermal/allergic rxn, GI sx, hypoglycemia

Question 13

CoQ10/Ubiquinone (oxidized) + Ubiquinol (reduced)

Answer 13

Fat sol compound synthesized in vivo
Antioxidant
Cellular respiration, ATP production, ETC
Membrane stabilizer, Preserves myocardial NaKATPase activity

Question 14

Vitamin A:

Answer 14

Antioxidant: Capable of quenching singlet oxygen/free radicals, Prevents lipid Peroxidation (with Vit C & E)
A + C are synergistic reducers for the risk of Lung cancer Smokers = supplement A + C together but do not supplement A alone for smokers
>25mg b-carotene intake may promote Tumorigenesis in Hepatocytes
Inducing elevated oxidized b-carotene = This blocks the conversion of b-carotene > retinoic acid in the lungs
*Retinoic Acid: Inhibits the activation of c-fos signaling system (increasing the % of cells in the g-phase = lowering risk of Lung cancer)
*Low Retinoic Acid = No inhibition of activation of c-fos signaling 
 (Increases % of cells being released from g-phase to s-phase (DNA replication cycle) = Increasing Lung cancer risk.
Primarily stored in Liver (stellate cells) in form of Retinyl Esters
Zinc Influences vitamin A status
Zinc is req to convert retinOl > retinAl (via alcohol dehydrogenase)
A reduction of zinc will reduce retinol-binding protein (RBP)
Primary fat soluble vitamin for Immune system
Night Vision

A Def: Appetite Loss & Frequent infections with Exercise

A Tox: Intracranial pressure, Irritability, Anorexia, Nausea/Vomiting, Blurred Vision, skin desquamation, Vertigo

Question 15

Vitamin A:

Answer 15

Antioxidant: Capable of quenching singlet oxygen/free radicals, Prevents lipid Peroxidation (with Vit C & E)
A + C are synergistic reducers for the risk of Lung cancer Smokers = supplement A + C together but do not supplement A alone for smokers
>25mg b-carotene intake may promote Tumorigenesis in Hepatocytes
Inducing elevated oxidized b-carotene = This blocks the conversion of b-carotene > retinoic acid in the lungs
*Retinoic Acid: Inhibits the activation of c-fos signaling system (increasing the % of cells in the g-phase = lowering risk of Lung cancer)
*Low Retinoic Acid = No inhibition of activation of c-fos signaling 
 (Increases % of cells being released from g-phase to s-phase (DNA replication cycle) = Increasing Lung cancer risk.
Primarily stored in Liver (stellate cells) in form of Retinyl Esters
Zinc Influences vitamin A status
Zinc is req to convert retinOl > retinAl (via alcohol dehydrogenase)
A reduction of zinc will reduce retinol-binding protein (RBP)
Primary fat soluble vitamin for Immune system
Night Vision

A Def: Appetite Loss & Frequent infections with Exercise

A Tox: Intracranial pressure, Irritability, Anorexia, Nausea/Vomiting, Blurred Vision, skin desquamation, Vertigo

Question 16

Vitamin E:

Answer 16

use w/ caution w/ anticoagulants, NSAIDS-anything else that encourages thinner blood.
Vitamin K & Vitamin E are antagonists (watch anticoagulants)
NOT a clinical sign of impaired wound healing
Used as preservative in Fish oil supplements

Def Contributes to ATAXIA – loss of ankle knee reflex, gait abnormality, speech changes (along with B12, B1)

Question 17

Vitamin D (Calcitriol aka 1,25-dihydroxyvitamin D aka 1,25(OH)2D)

Answer 17

Main function - form bones & teeth (out of all other fat-soluble vitamins)
Promotes efficient Calcium absorption in the GI tract
Renal hydroxylation of Calcidiol > Calcitriol (1-a-hydroxylase) is regulated (stimulated by either PTH, Hypophosphatemia or Hypocalcemia)
*Vit D indirectly promotes PTH/Osteoblast = mineralization of new bone
Vit D also Suppresses PTH production & increases osteoclast activity
this occurs via the balance of PTH + Calcitonin (osteoblast and osteoclast)

Def: lower Testosterone, Lower sperm quality Adequate Vitamin D intake is part of preconception care for men and women
Rickets = Children according to KRAUSE, children are highest risk for osteomalacia (amongst Elderly, athletes & post-meno women)
Osteomalacia = Adults AND CHILDREN
At risk: dark pigmented skin, >90% ppl with autoimmune thyroid disease have a Genetic defect affecting their metabolism of Vitamin D
Concurrent ingestion of Vitamin D enhances Phosphorus bioavailability

Question 18

Vitamin K:

Answer 18

Blood Clotting + Coagulation
Bone Metabolism
Regulate blood Calcium
The only Fat soluble vitamin WITHOUT TUL
Elevated Prothrombin Time (PT): Vitamin K deficiency, Ascites, Reduced production of clotting factors (associated with advanced liver disease)

Question 19

Calcium/Ca:

Answer 19

99% is reserved in skeletal bone/teeth, 1% is reserved for other functions…
Nerve Transmission, Stimulates Muscle contraction, bone metabolism, BP regulation, blood clotting (vit K)
Needed for vitamin D
*Ca is regulated by PTH, calcitonin, Vitamin D and Phosphorus (involving kidneys, GI tract, bone)
*Ca absorption (in GI tract) is enhanced by PTH to increase calcium reabsorption (bone breaking; OsteoCLAST) to maintain homeostasis
PTH = bone breaking hormone/osteoclast….stimulates Ca & P to leach out of bone > into plasma “bone resorption = bone breaking”
*Hypocalcemia = Triggers PTH to release Ca from bones & stimulate Ca absorption into GI tract
(Calcitonin works in opposite direction of PTH, by shutting off the release of Ca from bone and decreasing Ca absorption in GI tract)
Increased sodium causes increased Ca excretion
Caffeine = Increased calcium excretion; H2 blockers & PPI can decrease calcium
Calcium Citrate = Best for elderleys to absorb w/o need for HCl
Concurrent ingestion of Calcium decreases Phosphorus bioavailability
Ca Def: PARESTHESIAS of lips, tongue, fingers, Hypocalcemia = Tetany (muscle cramps, spasms)

Question 20

Potassium/K:

Answer 20

Most strongly associated with Low blood pressure (lowers sodium-potassium ratio = improved blood pressure)
Excess: Sx of impaired renal function & Tingling of hands & feet (Watch out w/ Potassium SPARING drugs)
K food sources: mango, dried beans, sweet potato, spinach, coconut, tomato, avocado, bananas, melon, swis chard, squash

Question 21

Sodium/Na:

Answer 21

Maintains Fluid balance “Wherever sodium goes, water will flow”

Question 22

Iodine/I:

Answer 22

*4 atoms make up T4/Thyroxine, BUT…TYROSINE = “backbone” of thyroid hormone not iodine
IODINE = CONSTITUENT IN PHYSIOLOGICAL ROLE of THYROID HORMONES not Selenium
Selenium deficiency exacerbates iodine deficiency (also Vit A and Iron)
DNI: anti-thyroid medications, ACE-inhibitors, potassium-sparing diuretics
Iodine Def: Cretinism/growth problems, Hypothyroid (goiter, faitue, weight gain), Elevated TSH, Preventable intellectual disability
At risk for Def: Pregnancy (neurodevelopent/growth retardation in fetus, miscarriage, excess goitrogens w/o eating Iodized salt
Tox: Black/bloody stools, irregular heartbeat, mental confusion, acne/dermatitis, >1-2mg inhibits thyroid function,
Food Sources: Processed Foods, Nori, Bread, Iodized Salt, COD, Mushroom

Question 23

Iodine/I:

Answer 23

*4 atoms make up T4/Thyroxine, BUT…TYROSINE = “backbone” of thyroid hormone not iodine
IODINE = CONSTITUENT IN PHYSIOLOGICAL ROLE of THYROID HORMONES not Selenium
Selenium deficiency exacerbates iodine deficiency (also Vit A and Iron)
DNI: anti-thyroid medications, ACE-inhibitors, potassium-sparing diuretics
Iodine Def: Cretinism/growth problems, Hypothyroid (goiter, faitue, weight gain), Elevated TSH, Preventable intellectual disability
At risk for Def: Pregnancy (neurodevelopent/growth retardation in fetus, miscarriage, excess goitrogens w/o eating Iodized salt
Tox: Black/bloody stools, irregular heartbeat, mental confusion, acne/dermatitis, >1-2mg inhibits thyroid function,
Food Sources: Processed Foods, Nori, Bread, Iodized Salt, COD, Mushroom

Question 24

Selenium/Se:

Answer 24

Antioxidant - Targets Hydrogen peroxide & converts to water, Fights oxidative stress
Synergistic with Vitamin E
Req for Glutathione Peroxidase
Converts lipid peroxidase into alcohol
Protects cells from oxidative damage
Inhibitors: Vanadium Interact Antagonistically w/ Selenium/Iodine
Se Def: Keshan’s Disease (heart disease as a result of Sel def) + infection
Selenium deficiency exacerbates iodine deficiency (also Vit A and Iron)
Se Toxicity (>400mg/d): Skin Rash, garlic or metallic breath, “Selenosis”-brittle hair/nails, Liver damage, Irritability
Food Sources: brazil nuts, tuna, poultry/meat, brown rice, sunflower seed, mushroom
Supplementation of Selenium is effective for treating AI thyroiditis and Dyslipidemia: *Improve T4-T3 conversion and supports Glutathione production.

Question 25

Vitamin C:

Answer 25

Reducing Agent (excess copper)
Vitamin C works in tandem with Copper to help reduce Iron to reduced Ferrous state (Fe2+)
Bioflavonoids (important part of vit C, found in pulp)
Increases absorption of non-heme Iron
Increases absorption of Estrogen/BCP, Aspirin, Anticoagulants
Leading vitamin (Antioxidant) for Collagen synthesis
Carnitine Synthesis (Transports LCFA into mitochondria for energy) body builders
High doses of Vitamin C may interfere w/ lab tests (oxalates, creatinine, bilirubin)
Deficiency: Scurvy, bleeding gums, poor wound healing
Toxicity: Diarrhea, Nausea
Inhibitors:
C Food sources: citrus, fruits, berries, bell pepper, broccoli

Question 26

Copper/Cu:

Answer 26

Ceruloplasmin (protein binding copper, ferroxidase enzyme) - Prevents free/oxidized copper ions from catalyzing oxidative damage
*Ferroxidase activity (oxidation of Ferrous iron (Fe2+) to oxidized Ferric (Fe3+)
*Ceruloplasmin supports binding oxidized Fe3+ to Transferrin (prevents free form Iron)
*high dose vitamin C (1,500mg) decreases ceruloplasmin
Cofactor associated with a number of oxygenases (oxidative phosphorylation)
Req for proper functioning of metalloenzymes (MAO, Tyrosinase Hydroxylase, PAH)
Copper Def: premature graying (also vitamin B12)
Possible causes of Cu def: high Iron, zinc (>50g zinc supplementation), B12 deficiency, Birth Control (pills/IUD)
**if Zinc is not helping titrating copper down (from Cu toxicity)…give Molybdenum! **Main sx = Anxiety
Toxicity: Kayser-Flischer rings, Wilson’s Disease (retain Cu excess), Menke’s Disease (recessive disorder coding ceruloplasmin)
Inhibitors: phytic acid, Fructose, Alcohol, zinc, Molybdenum
Cu Food Source: Organ meat, legumes, nuts, seeds, whole grain, chocolate

Question 27

Copper/Cu:

Answer 27

Ceruloplasmin (protein binding copper, ferroxidase enzyme) - Prevents free/oxidized copper ions from catalyzing oxidative damage
*Ferroxidase activity (oxidation of Ferrous iron (Fe2+) to oxidized Ferric (Fe3+)
*Ceruloplasmin supports binding oxidized Fe3+ to Transferrin (prevents free form Iron)
*high dose vitamin C (1,500mg) decreases ceruloplasmin
Cofactor associated with a number of oxygenases (oxidative phosphorylation)
Req for proper functioning of metalloenzymes (MAO, Tyrosinase Hydroxylase, PAH)
Copper Def: premature graying (also vitamin B12)
Possible causes of Cu def: high Iron, zinc (>50g zinc supplementation), B12 deficiency, Birth Control (pills/IUD)
**if Zinc is not helping titrating copper down (from Cu toxicity)…give Molybdenum! **Main sx = Anxiety
Toxicity: Kayser-Flischer rings, Wilson’s Disease (retain Cu excess), Menke’s Disease (recessive disorder coding ceruloplasmin)
Inhibitors: phytic acid, Fructose, Alcohol, zinc, Molybdenum
Cu Food Source: Organ meat, legumes, nuts, seeds, whole grain, chocolate

Question 28

Iron/Fe:

Answer 28

The Birth + Lifecycle of Iron:
Absorbed in Duodenum
*Req acidic gastric pH to convert Fe3+ > Fe2+
Easier absorbed/Usable form - Ferrous (Fe2+)
Oxidized/free form - Ferric (Fe3+)
Hepcidin (peptide hormone): Regulates iron absorb-distribution
Hepcidin is produced when Iron storage is HIGH; therefore, Hepcidin is a ferroportin inhibitor
*Ferroportin Inhibition = Iron remains trapped in cells, NOT excreted onto transferrin.
Iron Storage forms:
Ferritin - Major iron storage protein
Hemosiderin - secondary iron storage form
Iron Req acidic gastric pH to convert Fe3+ > Fe2+
Once Iron is absorbed, Fe2+ is converted back to Fe3+ (intestinal mucosa) & binds with apoferritin to form Ferritin
Apoferritin - Iron-free Protein present in the intestinal mucosa membrane
Apoferritin’s Function is to bind & store Iron by combining with a ferric hydroxide-phosphate compound (forms Ferritin, storage form of Iron)
Apoferritin = not bound to Iron apo = without iron
Ferritin = bound to Iron (Fe3+
Ferroportin (Iron export protein) - Located on surface (enterocytes)….Transports Iron from Inside > outside of cell (to be transported into bloodstream)
Transferrin (Iron binding protein) - “Iron-transferrin complex” (ensures there is NO free floating oxidized Iron)
**Ferroportin (“door”) transports iron outside ONTO transferrin (“Transport Truck”) to portal blood.
Here, Ferric (Fe3+) bound to Ferritin = Transferrin) in the portal blood has options:
It can connect with Bone Marrow to synthesize Erythropoietin (new RBC), which occurs in the KIDNEYS.
This is KEY for recycling Iron to make new RBC. If Iron does not reach Bone marrow, “Soluble Transferrin Receptors” will elevate indicating the need for Iron.
Synthesis of Erythropoietin (new RBC). Remember, RBC are “born big, and grow small” so this is where vitamin B9 and B12 are important to ensure the RBC shrink, to make sure Iron can get cycled through the system.
It can enter Iron storage sites (Primarily the liver, but also spleen, marrow, duodenum, skeletal muscle)
It can enter the Liver to stimulate Hepatocytes and downregulate Ferroportin or inhibit Macrophages from releasing more Iron.
The Copper + Iron Relationship:
Copper is req for binding Ferric/Fe3+ onto Transferrin (so oxidized/free iron is not dangerously floating around after its excreted by Ferroportin)
*Ceruloplasmin (protein binding copper, ferroxidase enzyme) - Prevents free/oxidized copper ions from catalyzing oxidative damage
*Ferroxidase activity - The oxidation of Ferrous iron (Fe2+) to oxidized Ferric (Fe3+)
*Ceruloplasmin supports binding oxidized Fe3+ to Transferrin (prevents free form Iron)
Fenton Reaction: Occur when Copper is absent; Oxidized Fe3+ float around portal blood (not bound to Transferrin), and cause oxidative stress/Hydroxyl radicals
Iron Regulatory Element (IRE in cytosol): Binding of IRE-BP + Iron is a response to the presence of Low intracellular Iron (low ferritin)
IRE regulates iron metabolism…by binding to Iron, it regulates the expression of mRNA that encodes for the proteins involved in iron uptake, storage, | 
 usage and export.
Heme Iron is formed when Iron + protoporphyrin IX contributes to 10-15% TTL iron intake (w/ b6, zinc)
*From my understanding, after Heme is formed, Iron can dissociate from Heme and get recycled back into the system.
Erythrocytes are the last to show evidence of Iron deficiency **Ferritin is the better indicator of IDA than hemoglobin
Hematocrit - Represents % of RBC (Vol RBC/TTL Value)
Watch Vitamin A and Copper (make sure there are enough of each)
Iron can block zinc absorption (when taken together)
Req’ to synthesize b3 from Tryptophan (also Mg, b6, b2)
15mg needed for young girls starting menses
27mg needed for pregnancy
Dosage remains the same for men 25-75yo
Infant formula fortified with 12mg Iron/L
For Anemic Clients: Supplement Iron w/ Vitamin C, and take separate from Dairy
Take Iron on empty stomach (only 50% supplement is absorbed if taken with food)
**Lucky Iron Fish: cast iron fish = put fish into pot with lemon juice to increase iron in cooking.
Hemochromatosis: Iron overload
DNI: H2 Blockers, PPI, ACE inhibitors, Antibiotics, Aspirin

Enhancers: Vitamin C, dietary sugar, alcohol, amino acids, stainless steel cooking
Inhibitors: Phytic Acid, Polyphenols (tannins, tea), Cobalt, Mn, Soy protein inhibit absorption of non-heme iron
 Dairy/calcium Induced Iron Deficiency Anemia for children <1yo

Def: Restless leg syndrome (Fe def affects Tyrosine hydroxylase, synthesizing dopamine), anemia, fatigue, impaired immune function, headache
Fe Food sources: meat, Legumes, organs, seafood, spinach, baked beans, apricots

Question 29

Zinc/Zn:

Answer 29

Alkaline Phosphatase: Zn dep, used to assess zn def
Cofactor for Carbonic anhydrase (converts carbonic acid to be excreted for acid/base balance)
Folate & Vitamin A support Zinc
watch DIURETICS
Zinc is Primarily assessed through dietary intake bc no reliable functional test exists
Optimal zinc status is important for preconception in Men
Def: Cold sores, taste alterations, alopecia, diarrhea, bullous-pustular dermatitis
Toxicity:
Inhibitors:
 Zn Food sources:

Question 30

Manganese/Mn:

Answer 30

Cation
MnSOD—Manganese Superoxide Dismutase: Mitochondrial Enzyme, Antioxidant, Detox ROS
SOD req Zn, Cu (cytoplasm)
SOD req Se, Mn (Mitochondria)…convert O2 > Hydrogen Perox. (H2O2)…for Glutathione Peroxidase activity, GSH (reduced) (Se) > GSSG (oxidized))
Support urea cycle, urea production & connective Tissue
Cofactor for Transketolase (b1), Superoxide Dismutase, Acetyl CoA Carboxylase
Quinapril/Accupril provides 50-200mg/day
Mn Used for arthritis pain, SOD, glutamine production, bone development, wound healing, seizures
Inhibitors: Iron, Calcium, Magnesium, Phytic Acid, Oxalates


Mn Food Sources: Pineapple, Almond Butter, Tea, whole grain, cereal, nut, beans, egg yolks, bananas, acai, Dark chocolate

Question 31

Manganese/Mn:

Answer 31

Cation
MnSOD—Manganese Superoxide Dismutase: Mitochondrial Enzyme, Antioxidant, Detox ROS
SOD req Zn, Cu (cytoplasm)
SOD req Se, Mn (Mitochondria)…convert O2 > Hydrogen Perox. (H2O2)…for Glutathione Peroxidase activity, GSH (reduced) (Se) > GSSG (oxidized))
Support urea cycle, urea production & connective Tissue
Cofactor for Transketolase (b1), Superoxide Dismutase, Acetyl CoA Carboxylase
Quinapril/Accupril provides 50-200mg/day
Mn Used for arthritis pain, SOD, glutamine production, bone development, wound healing, seizures
Inhibitors: Iron, Calcium, Magnesium, Phytic Acid, Oxalates


Mn Food Sources: Pineapple, Almond Butter, Tea, whole grain, cereal, nut, beans, egg yolks, bananas, acai, Dark chocolate

Question 32

Molybdenum/Mo:

Answer 32

Cation
Req’ cofactor for Xanthine oxidase (met’ of purine/pyrimidines), Aldehyde, Sulfite Oxidases
E- transfer agent in ox-reduction rxn
Associated with Gout & uric acid (byproduct of purine metabolism)
Mo Food sources: Meat, legumes, cereal, peas, beans, Nuts

Question 33

Molybdenum/Mo:

Answer 33

Cation
Req’ cofactor for Xanthine oxidase (met’ of purine/pyrimidines), Aldehyde, Sulfite Oxidases
E- transfer agent in ox-reduction rxn
Associated with Gout & uric acid (byproduct of purine metabolism)
Mo Food sources: Meat, legumes, cereal, peas, beans, Nuts

Question 34

Magnesium/Mg:

Answer 34

Supports chronic disease; inhibition of inflammation
Inhibits Muscle Contraction
High dose zinc decreases magnesium absorption
Higher protein intake INcreases magnesium absorption
Calcitonin: Inhibits release of calcium from bones (osteoclast); Lowers Ca2+ Blood
Magnesium stimulates the Thyroid’s production of Calcitonin (bone-preserving hormone)
Req’ to synthesize b3 from Tryptophan (also Iron, b6)
Magnesium Supplementation shown to increase testosterone in males who exercise (likely to be loss through sweat) (HK, p73)
Watch for certain classes of ANTIBIOTIC interactions
Inversely related to systemic inflammatory C-reactive protein

Question 35

Chloride/Cl:

Answer 35

Important for production of hydrochloric acid

Question 36

Chromium/Cr:

Answer 36

Potentiates action & effects of Insulin (transports glucose into cells)
Influences plasma glucose by stimulating myocyte sodium-glucose transport
Hexvalent chromium is carcinogenic and classified as carcinogen when inhaled
DNI: Antacids
Inhibitors: Concurrent ingestion of Calcium carbonate, CHO increases Chromium excretion, cooking
Enhancers: b3/Niacin, Vitamin C
Cr Def: glucose intolerance, Elevated Chol/Trig, aortic plaques, fatigue
Cr Food sources: b yeast, grains, salmon, honey

Question 37

Vanadium/V:

Answer 37

Mimics effects of Insulin on adipocytes
Regulates sodium/Hydrogen Ion transporter
Stimulates Osteoblast activity
Food Source: Shellfish, black pepper, parsley, dill seeds, canned apple juice, fish sticks, grain, beer, wine, mushroom, sweeteners

Question 38

Demographics at risk:

Answer 38

African-American women tend to have higher levels of Ferritin vs Caucasian Women.
African-Americans (primarily), Southeast Asian & editerranean are at increased risk for sickle cell disease/thalassemia.
Hypertension: Affects Men & Women in nearly equal proportions
African-Americans have amongst highest prevalence of Hypertension in the world. (especially Elderly African-Americans = Salt-sensitive)
RYGB: Up to 50% of patients who have undergone RYGB have iron deficiency 4y post-op, and RYGB is 2x more common in females compared to males
Iron Deficiency: populations at risk include menstruating, pregnant females, infants, children and those with celiac disease
Prevalence of prenatal iron deficiency is higher in African-American women, Low-income women, teeneaters and those w/ less than high-school 
 education or those who have had 2 prior pregnancies.
Gestational Diabetes: Rates are higher in African-Americans, Hispatic, Native and Asian women vs white women.
For high-risk clients, screen at first prenatal visit or by 16 weeks.
High risk patients are those w/ personal history of abnormal glucose tolerance, obesity, 1st degree relative with T2D, ethinic group
Diabetes Screening in Children:
High risk race/enthnic group (African-American, Native/Asian American, Pacific, Latino)
Obesity: Prevalence is higher among African-Americans and Hispanics (in US)
Females retain higher BF% and low LBM compared to males
BMI: Overestimates BF in muscular people, underestimates BF in underweight people (elderly, anorexic)
Amenorrhea = more common among female athletes than the general population

Vitamin K deficiency:
Infants and those on antibiotics; Studies of elderly patients w/ Osteoporosis have demonstrated greater rates of K insufficiency (but long-term 
 clinical trials with K supplements produced mixed results regarding benefits preventing osteoporosis)
Atherosclerotic Vascular Disease (AVD): risk for males <55yo and females <65yo
Risk factor for constipation:
Age, female gender, women 2x more likely to report constipation sx compared to men (HK, p295)
Cholelithiasis (combination of lithogenic bile, cholesterol crystallization, gallbladder stasis):
Risk factors involve Female gender, pregnancy, age, obesity and certain ethnic backgrounds.
3 Largest risk factors for Sleep Apnea: Obesity, Male gender, Middle-age
For Adults with Cystic Fibrosis:
Caucasians at high risk for CF
The goal for females is to maintain a BMI >22kg/m2 and Males to maintain a BMI > 23kg/m2 (Ct with CF have high resting energy expenditure due to
increased work of breathing, inflammatory responses and infections).
Breast cancer: Most common cancer in women, developed & developing countries (16% of all female cancers)
Colorectal Cancer (CRC):
3rd most common malignancy in the US, and 3rd leading cause of cancer mortality rates in men & women
Males have a higher mortality rate than women.
Groups who have Increased req’ vitamin & mineral intake: Elderly, pregnant, lactating women, growing children, those who have suffered severe trauma (burns, fractures, surgery), those at high risk for infections (HIV, malabsorption syndromes), exces consumers of alcohol, substance abuse users, those taking medications that interfere with absorption/metabolism of nutrients.
African-American & Japanese Men/Women have higher COLON cancer incidence rates (Hispanics, Asian/pacific, Native americans have lowest rates)
Lactase Deficiency: (HK, p289)
Naturally declines with Age
Suggests a certain genetic predisposition, Lactose malabsorption occurs appx. 5-20% of Caucasians, but high as 50-80% in Latinos and 60-80% 
 amongst African-Americans/Jews and nearly 100% in Asians/American Indians.
Older Adults (HK, p197):
72m americans will be >85yo by 2030 (19% of population)
Women continue to outnumber men, by 2030, Hispanics, Asian/Pacific, Native, African-Americans will present approximately 25% of elderly
population.
Vitamin D RDA men/women >51yo is 600IU/day and >70yo is 800IU/day TUL for adults is 2000IU/day
Iron RDA men/women >51yo is 8mg/day TUL 45mg/day
In elderly patients, the main cause of large intestinal obstruction is colon cancer (70%) followed by diverticulitis (5%) and volvulus (10%).

Question 39

ACID-BASE
Blood pH:

Answer 39

7.35-7.45

Question 39

ACID-BASE
Blood pH:

Answer 39

7.35-7.45

Question 40

Metabolic Acidosis (Lungs)

Answer 40

Hyperkalemia
Vomiting, Diarrhea, Nausea + warm/flushed skin
CHRONIC RENAL FAILURE, DIABETIC, OBESE (CRF-H ions arent properly being excreted. A Positive acid balance often leading to a reduction of serum 
 bicarbonate concentration may be observed in CKD).
Lactic Acidosis/Diabetic Ketoacidosis (DKA)

Question 41

Metabolic Acidosis (Lungs)

Answer 41

Hyperkalemia
Vomiting, Diarrhea, Nausea + warm/flushed skin
CHRONIC RENAL FAILURE, DIABETIC, OBESE (CRF-H ions arent properly being excreted. A Positive acid balance often leading to a reduction of serum 
 bicarbonate concentration may be observed in CKD).
Lactic Acidosis/Diabetic Ketoacidosis (DKA)

Question 42

Metabolic Alkalosis (Lungs) - lose excess Acid, Accumulate excess HC03.

Answer 42

Hypokalemia
Excess vomiting, diarrhea, Nausea
Excess Antacid usage
Diuretics (diuretics increase urinary acid excretion)

Question 43

Respiratory Acidosis

Answer 43

Hypoventilation-hypoxia (no breath = pH drops = acid builds)
Hyperkalemia
Drowsiness, dizzy, disorientation
COPD, Pneumonia, drug overdose
Emphysema (obstructive lung/bronchitis/pneumonia)

Question 44

Respiratory Alkalosis

Answer 44

Hyperventilation / deep, rapid breathing (too much breath = pH increases = acid drops)
Hypocalcemia
Hypokalemia
Seizures, Lethargy, confusion
Anxiety, Fever, Infection, Mechanical ventilation
Possible causes of respiratory Alkalosis: heart Failure, Meningitis (viral infection), Pregnancy