Final Exam Material Flashcards

Question

Describe the symptoms of zinc toxicity, both acute (3) and chronic (2).

Answer 1

* **Acute toxicity** * Vomiting * Abdominal cramps * GI distress * **Chronic toxicity** * Copper deficiency * Anemia → copper is needed for the transport of iron

Answer 2

* Zinc is important for immune function. * Overall, research suggests that high dose zinc supplements taken at the onset of a cold (i.e., the start of noticeable symptoms) may reduce onset and duration.

Answer 3

Zinc is an **essential micromineral,** or trace element Mostly occurs in the body in the form of Zn²⁺

Answer 4

False. * Zinc content of foods often associated with protein content of foods.

Answer 5

False. * Plant sources have less zinc and zinc is less well absorbed from plant sources.

Answer 6

RDA → based on amount needed maintain balance as well as on estimates of zinc absorption and body losses Tolerable Upper Intake Level = 40mg/day

Answer 7

Answer → C

Answer 8

* Minor pathways; * DMT1 * With amino acids via amino acid carriers * Paracellular diffusion at high intakes (\>20 mg)

Answer 9

ZIP-4 degraded with high Zn status

Answer 10

* 20-50% of ingested zinc is absorbed * Absorption rate is influenced by zinc **intake** and **enhancers/inhibitors**

Answer 11

* Less absorption with higher intakes * 100% absorbed at intake levels \<1mg * 30-40% absorbed at intake level of about 12mg

Answer 12

* Amino acids, organic acids → form soluble complexes with zinc * Higher acidity

Answer 13

* (1) Phytic acid, (2) oxalic acid, (3) polyphenols → form complexes with zinc that are not absorbed * (4) Non-heme iron (particularly at high doses)

Answer 14

* Used intracellularly for biochemical functions * Stored, or sequestered in vesicles or Golgi network * Transported through the cytosol bound to proteins, across the basolateral membrane (through ZnT1)

Answer 15

False. Zinc is bound to proteins (e.g., albumin) or amino acids in plasma.

Answer 16

Bound to proteins (e.g., albumin) or amino acids

Answer 17

* ZIPs as importers; also DMT1 * Zinc transporters (ZnTs) as exporters

Answer 18

* Zinc is bound to proteins in: * Nucleus (30-40%) * Cytosol (50%) * Cell membrane (10%)

Answer 19

False. Metallothionein has a higher affinity for copper than zinc → copper bound to metallothionein in enterocyte become ‘trapped’ → higher zinc in the body stimulates synthesis of **metallothionein in enterocyte** → *zinc-induced copper deficiency possible*

Answer 20

True. Copper bound to metallothionein in enterocyte become ‘trapped’ → higher zinc in the body stimulates synthesis of **metallothionein in enterocyte** → *zinc-induced copper deficiency possible*

Answer 21

* Storage complex for zinc * Intracellular transport of zinc * Detoxifying heavy metals * Stabilizing membranes * Antioxidant

Answer 22

False. * A zinc-induced copper-deficiency is possible because higher zinc in the body stimulates metallothionein synthesis in enterocyte → metallothionein has a higher affinity for copper than zinc

Answer 23

True. A zinc-induced copper-deficiency is possible because higher zinc in the body stimulates metallothionein synthesis in enterocyte → metallothionein has a higher affinity for copper than zinc

Answer 24

Answer → A Amino acids and organic acids can form soluble complexes with zinc that enhance absorption.

Answer 25

Answer → B Zinc is not excreted through biliary excretion mechanisms.

Answer 26

Zn²⁺ provides **structural integrity** to enzymes and participates in reaction at **catalytic site**.

Answer 27

* Antioxidant function through role in Cu/Zn superoxide dismutase (SOD) * Synthesis and degradation of proteins, carbohydrates, lipids, DNA and RNA → zinc functions as cofactor for various enzymes including kinases, phosphorylases, polymerases * Digestion of nutrients (e.g., folate hydrolase, alkaline phosphatase) * Wound healing (matrix metalloproteinase) * Taste (gustin)

Answer 28

* Zinc fingers → structural role regulating gene transcription (e.g., estrogen receptor; glucocorticoid receptor

Answer 29

Answer → D

Answer 30

Answer → C

Answer 31

Answer → D Impaired copper absorption is an effect of zinc toxicity not deficiency.

Answer 32

True. 40 mg/day

Answer 33

False. Zinc UL = 40mg/day

Answer 34

* ATP7A is needed to release Cu from the enterocyte into the blood. * Lack of ATP7A leads to impaired release of copper from enterocytes (= decreased absorption → **copper deficiency**) * Impaired uptake of copper across blood-brain barrier by the brain which leads to neurological deficits that cannot be corrected. * ***Deficiency symptom** → implicated metalloenzyme* * **Steely depigmented hair** → tyrosinase * **Ruptured arteries** → lysyl oxidase * **Reduced bone mineral density** → lysyl oxidase * **Brain & cognitive abnormalities** → decreased synthesis and degradation of neuropeptides due to impaired transport across BBB and also cytochrome C oxidase is important in synthesis of myelin

Answer 35

* Impaired excretion of copper in bile (= **copper toxicity**) * Impaired secretion of ceruloplasmin (= main copper transporter → lower transport in blood despite toxicity)

Answer 36

* Meats (organ meats), shellfish, legumes, nuts, and seeds * In food → mainly Cu²⁺ bound to a.a./proteins * In supplements → copper sulfate and other complexed forms

Answer 37

* Release of Cu²⁺ from food components via digestive enzymes in stomach and small intestine * Reduction of Cu²⁺ → Cu⁺ (main absorption form = Cu⁺) * Occurs in stomach (low pH) and * By reductases in the small intestine

Answer 38

* Where → mainly duodenum * How → mainly as cuprous (Cu⁺) * (1) Carrier mediated through Copper transporter 1 (Ctr1) → synthesis may be inversely related to status * (2) DMT1 * Overall absorption rate → absorption efficiency inversely related to dietary intakes and body copper status

Answer 39

* **Intracellular movement of copper via chaperone proteins** → prevents pro-oxidant effects of copper; transfers copper to various enzymes * **ATP7A** → transport of copper through the basolateral membrane of enterocyte; release of copper from most cells (except liver); transport of copper across blood-brain barrier * **ATP7B** → transport of copper into golgi for synthesis of copper containing enzymes & ceruloplasmin; export of copper into bile duct for excretion

Answer 40

* Shuttled and transferred into Golgi network via **ATP7B** → incorporation into **ceruloplasmin** and other **copper-metalloenzymes** * With excess copper, ATP7B moves Cu⁺ to vesicles → into **bile** duct for secretion into intestine * **Storage**, bound to **metallothionein**

Answer 41

* Fecal (95%) * Biliary excretion as homeostatic mechanism * Copper bound to bile components, cannot be reabsorbed! * Copper excretion into bile involves ATP7B

Answer 42

* Shuttled and transferred into Golgi network via ATP7B → incorporation into ceruloplasmin and other copper-metalloenzymes * With excess copper, ATP7B moves Cu⁺ to vesicles → into bile duct for secretion into intestine * Storage, bound to metallothionein

Answer 43

1. Antioxidant function: Cu/Zn superoxide dismutase (SOD) 2. Iron transport: ceruloplasmin and hephaestin 3. Electron transport chain 4. Pigment (melanin) synthesis: tyrosinase 5. Collagen synthesis (in lysyl oxidase) 6. Hormone activation 7. Neurological roles

Answer 44

* High **zinc** intake stimulates intestinal metallothionein which binds copper and prevents absorption (= zinc induced copper deficiency) * Copper is needed for **iron** transport through ceruloplasmin or hephaestin which oxidize iron so that it can bind transferrin * **Vitamin C** (a.k.a. ascorbic acid) maintains copper in reduced state for enzyme function

Answer 45

* Menke's genetic disorder * High zinc intake * Impaired absorption (e.g., atrophic gastritis, IBD)

Answer 46

* ***Deficiency symptoms** → Cu-metalloenzyme activity* * **Anemia** → lower hephaestin or ceruloplasmin → lower iron oxidation and transport * **Weakened bones** → decreased lysyl oxidase → decreased collagen and elastin * **Vascular dysfunction** → decreased lysyl oxidase → decreased collagen and elastin which are important in arterial function * **Depigmentation of skin and hair** → decreased tyrosinase which produces melanin → reduced melanin synthesis

Answer 47

* No consensus on best biomarker to use → partially because of efficient homeostasis of tissue copper concentrations * (1) Serum/plasma copper and (2) serum ceruloplasmin → reliable only for severe deficiency; not sensitive enough to detect marginal Cu-deficiency * (3) Erythrocyte superoxide dismutase activity → more sensitive indicator of copper depletion than serum copper or ceruloplasmin

Answer 48

* Copper has a UL = 10mg/day * Acute toxicity → abdominal pain; nausea; vomiting * Chronic toxicity (rare) → liver damage

Answer 49

Answer → B

Answer 50

False. Menke's is a genetic disorder resulting in copper deficiency.

Answer 51

False. Wilson's is a genetic disorder resulting in copper toxicity.

Answer 52

Steely depigmented hair Ruptured arteries Reduced BMD Anemia Brain & cognitive abnormalities

Answer 53

Liver disease Impaired motor control and brain damage if untreated

Answer 54

Onset at birth Poor prognosis with life expectancy \<10 years

Answer 55

Onset between 5 - 35 years With treatment normal & healthy life

Answer 56

False. There is no treatment for Menke's disease

Answer 57

Copper is an **essential** **micromineral**, or trace element Occurs in two forms: Cu²⁺ (cupric) Cu⁺ (cuprous)

Answer 58

RDAs for copper Depletion/repletion studies and on studies estimating obligatory losses of copper over a range of intake allowed the estimation of requirements

Answer 59

Answer → A ## Footnote **1 milligram (mg) is equal to 1000 micrograms (μg)**

Answer 60

False. Absorption efficiency of copper is inversely related to dietary intakes and body copper status.

Answer 61

False. Copper transporter 1 synthesis may be **inversely** related to copper status.

Answer 62

Answer → D Legumes, nuts, seeds

Answer 63

* Passage through basolateral membrane via **ATP7A,** a copper transporting ATPase (= active transport) * Transport through hepatic portal blood bound to proteins (mostly albumin) * Liver uptake via multiple carrier proteins, such as Ctr1, Ctr2, DMT1, and other unidentified carriers.

Answer 64

* Transport of copper through basolateral membrane of enterocyte * Release of copper from most cells (except liver) * Transport of copper across the blood-brain barrier

Answer 65

* Transport of copper into golgi for synthesis of copper containing enzymes & ceruloplasmin * Export of copper into bile duct for excretion

Answer 66

* Secreted from liver * Main transporter of copper in blood plasma

Answer 67

* Uptake of ceruloplasmin into tissues via receptors * In cells, bound to chaperone proteins * Use for: biochemical needs, storage, or transport out * Release of copper from cells via ATP7A (expressed in most body cells, except liver)

Answer 68

* Bound to metallothionein * Copper influences hepatic, renal, and brain metallothionein synthesis, but not intestinal metallothionein synthesis.

Answer 69

False. Copper influences hepatic, renal, and brain metallothionein synthesis, but not intestinal metallothionein synthesis.

Answer 70

Answer → C

Answer 71

Cu/Zn superoxide dismutase (SOD)

Answer 72

Ceruloplasmin (= liver) and hephaestin (= basolateral membrane) → oxidation of iron, which is required for cellular iron release and binding to transferrin * Ceruloplasmin is also important for: * Transport of copper in plasma * Antioxidant - important in inflammatory process

Answer 73

Cytochrome c oxidase = terminal oxidation step in ETC

Answer 74

Melanin synthesis → tyrosinase

Answer 75

Via lysyl oxidase * Iron and vitamin C required for hydroxylase * Copper required for lysyl oxidase → **cross-linking of tissue proteins**

Answer 76

Cu required for amidation of peptide hormones → crucial for hormone function Hormones include: gastrin, cholecystokinin, calcitonin, thyrotropin, vasopressin, etc.

Answer 77

* Biogenic amine degradation (in **amine oxidases**) * Including histamine, dopamine, serotonin, norepineprhine * Norepinephrine synthesis (**dopamine monooxygenase**) * **Cytochrome C oxidase** is important in synthesis of myelin.

Answer 78

Answer → D

Answer 79

Rare in adults → more likely with high Zn intake (\>40mg/day) or conditions/medications that reduce Cu absorption

Answer 80

Answer → B

Answer 81

* ATP7B is required for secretion of ceruloplasmin from liver, deficiency decreases its concentration → inability to secrete it means the liver will store more with metallothionein

Answer 82

False. Copper UL = 10mg/day

Answer 83

True. Copper UL = 10mg/day

Answer 84

**Scurvy →** first vitamin deficiency to be prevented (1753 ‘*Treatise on the Scurvy*') * **Fatigue and weakness** → may be related to reduced carnitine synthesis * **Impaired collagen synthesis** leading to: [5] * Small, red skin discolouration caused by ruptured small blood vessels * Easy bruising * Swollen, bleeding, necrotic gums * Loose decaying teeth * Impaired wound healing * **Fatal**, if untreated * *Development of scurvy in as little as 1 month!*

Answer 85

1. **Inadequate intake** → limited food variability 2. **Smoking** (accelerates the depletion of the body's ascorbic acid pool) → smokers need more vitamin C 3. **Certain diseases** 1. GI diseases/conditions that cause malabsorption 2. Some types of cancer → increased vitamin C turnover 3. Diabetes → increased urinary excretion

Answer 86

* Vitamin C = **ascorbic acid** (reduced & active form) * **Dehydroascorbic acid** (oxidized form → can be reduced to ascorbic acid) * No endogenous synthesis of vitamin C in humans (cats can synthesize it!)

Answer 87

1. **Antioxidant activity** → neutralizes ROS 2. **Co-substrate for enzymes/reducing agent [4]** 1. Collagen synthesis 2. Carnitine synthesis 3. Neurotransmitter synthesis 4. Hormone synthesis 3. **Other functions [2]** 1. Possible role in gene expression 2. Enhances immune function

Answer 88

1. Vitamin C and **_iron & copper_** interactions 1. Vitamin C = reducing agent 2. Vitamin C enhances the intestinal absorption of non-heme iron (Fe³⁺) and copper by reducing them into appropriate oxidation state for absorption, i.e., Fe²⁺, Cu⁺ 2. Vitamin C and **_vitamin E & niacin_** 1. Vitamin C = reducing agent

Answer 89

* **Food sources** → fruits and vegetables * **Forms in food** → ascorbic acid (main), dehydroascorbic acid * **Forms in supplements** → ascorbic acid, calcium ascorbate, sodium ascorbate, dehydroascorbate → absorption does not appear to differ between forms

Answer 90

None required!

Answer 91

* **Where** → small intestine, especially proximal jejunum * **How** * _(1) Ascorbic acid_ → **sodium-dependent** vitamin C transporters (SVCT1 and SVCT2) → SVCT1 = main → down-regulated by vitamin C * _(2) Dehydroascorbic acid_ → glucose transporters (GLUT) * **In enterocyte** → rapid reduction of dehydroascorbic acid → ascorbic acid * **From enterocyte** → ascorbic acid diffuses through ion channels in the basolateral membrane → capillaries → hepatic portal vein → liver (just like other water-soluble vitamins)

Answer 92

* Transport of vitamin C from liver to extrahepatic tissues → in **free form** in blood as ascorbic acid (main) or dehydroascorbic acid (minor) * Cellular uptake/tissue uptake * Ascorbic acid via SVCT1 and SVCT2 * Dehydroascorbic acid via GLUTs (i.e., glucose transporters) → reduced intracellularly to ascorbic acid via glutathione-dependent reductase

Answer 93

* Oxidized to dehydroascorbic acid * Further metabolized to oxalic acid and other products * Oxalic acid contributes to formation of kidney stones → at high intakes

Answer 94

* Excretion through urine * Intact or catabolized, depending on level of vitamin C intake and status * Reabsorbed through SVCT1 * When SVCT1 in renal tubules saturated = upper limit of renal absorption

Answer 95

* **No serious adverse effects** * Most common symptoms: * Diarrhea * Nausea * Abdominal cramps * Other GI disturbances → due to the osmotic effect of unabsorbed vitamin C in the GI tract * Tolerable Upper Intake Level (UL) for vitamin C = 2000mg/day (2g/day) for adults

Answer 96

Clinical evidence: * No benefit of pharmacological doses \>1-2 g per day * Regular use does not prevent colds * Regular usage (≤ 1 g/day) **may decrease** the **duration** and **severity** of symptoms * Regular use may decrease incidence of colds in individuals under extreme physical stress (e.g., marathon runners, soldiers exposed to extreme temperatures, etc.) * Note → intravenous vitamin C is often used when people are hospitalized to mitigate cytokine storms

Answer 97

Answer → C

Answer 98

Answer → C

Answer 99

Answer → D

Answer 100

Answer → B

Answer 101

Answer → C

Answer 102

* Powerful **antioxidant/reducing agent,** providing H⁺/e^- * By providing H⁺/e^-, ascorbic acid **neutralizes ROS** * **Regeneration of other antioxidants**, e.g., vitamin E and glutathione

Answer 103

* Vitamin C functions as a **reducing agent** to maintain metal ions (copper and iron) in reduced state in metalloenzymes. * Co-substrate for enzymes in: * **Collagen synthesis** → requires iron and copper as cofactors; vitamin C regenerates their reduced forms * **Carnitine synthesis** → requires iron; vitamin C regenerates reduced form → important for amino acid metabolism * Carnitine plays a **critical role in energy production**. It transports long-chain fatty acids into the mitochondria so they can be oxidized ("burned") to produce energy. It also transports the toxic compounds generated out of this cellular organelle to prevent their accumulation. * **Hormone synthesis** e.g., gastrin cholecystokinin, calcitonin, vasopressin, etc. → copper is required; vitamin C regenerates its reduced form

Answer 104

* **Enhances immune function** → mechanisms unclear but may involve its antioxidant capacity, as well as: * Increased production and activity of immune cells * Promoting chemotaxis (i.e., recruitment of immune cells to sites of infection) * Increased production of complement proteins

Answer 105

**Stability** → destroyed by heat, light, oxidation and pH \> 7; stable at pH \< 7

Answer 106

RDAs (mg/day) → 75 mg/day for me Based on estimations to nearly maximize tissue concentrations and minimize urinary excretion → smokers recommended to take additional 35mg vitamin C daily

Answer 107

* Absorption **efficiency is dose-dependent** = absorption rate is **inversely related with the intake level**: * 70-95% at normal range (30-180 mg/day) * 98% at \<20mg * ~50% at \>1g * 16% at 12g * **Regulated through transporter in brush border membrane → SVCT1** * Relevance of reducing absorption efficiency with increasing intake * Prevention of symptoms of excess → protect against toxicity * Avoidance of symptoms of deficiency

Answer 108

False! UL = 2000mg/day Common symptoms: * Diarrhea * Nausea * Abdominal cramps * Other GI disturbances

Answer 109

False. Vitamin C has a UL (2000mg/day) because of common symptoms (e.g., diarrhea, nausea, abdominal cramps, GI distress)

Answer 110

* Evidence from correlational studies: * Increased intakes of fruits/vegetables → decreased risk of cancer and CVD * Proposed mechanism: * Vitamin C can limit the formation of carcinogens, modulate immune response, and attenuate oxidative damage that can lead to cancer and CVD * Evidence from clinical trials: * No protective or therapeutic benefits of vitamin C

Answer 111

Answer → B It may reduce the duration and severity, but it will not prevent colds.

Answer 112

No appreciable storage of vitamin C in the body as it is a water-soluble organic compound.

Answer 113

Ascorbic acid

Answer 114

* Vitamin E encompasses 8 compounds/vitamers → 2 classes each with 4 forms * Classes: * Tocopherols with _saturated_ side-chains * Tocotrienols with _unsaturated_ side-chains * Forms per class → differ in the number and location of the methyl group on the chromanol ring * α * β * γ * δ * Different forms are **NOT** interconvertible * **α****-tocopherol is the main biologically active form**

Answer 115

* Tocopherols contain 3 chiral centres with a configuration of R or S (used to designate stereoisomers of asymmetrical molecules like vitamin E) * Naturally occurring and most biologically active form = **RRR-****α****-tocopherol** * 2R-stereoisomeric forms (RSR-, RRS-, RSS-) of α-tocopherol have _some_ activity * 2S-stereoisomeric forms (SSR-, SSR-, SRS-, SSS-) disappear rapidly from plasma and have _very little_ activity

Answer 116

* In food → various forms, but α-tocopherol is the one retained in the body * Food sources → primarily found in plant foods, especially nuts, seeds, and oils; animal products are inferior * In supplements and fortified foods → all-racemic α-tocopherol (i.e., all possible stereoisomers of α-tocopherol): α-tocopheryl acetate or α-tocopheryl succinate

Answer 117

* None for tocopherols * Hydrolysis of synthetic tocopherol esters by **esterases** from pancreas and small intestine

Answer 118

* Where → jejunum * How → micelle formation with dietary fat and bile salts; diffusion of micelles across brush border membrane * Simultaneous ingestion of dietary fats improves absorption of vitamin E.

Answer 119

* **Enterocyte** → incorporation into chylomicrons → passage through basolateral membrane → into lymphatic system → blood circulation at thoracic duct * **Uptake of chylomicron content** → lipoprotein lipase → hydrolysis of chylomicrons → release of fatty acids and vitamin E for uptake * **Chylomicron remnants** contain various vitamin E forms → transported to liver * **In liver** → hepatic metabolism occurs specific to α-tocopherol → incorporation of α-tocopherol into VLDL by α-tocopherol transfer protein (α-TTP) → release into blood * Other forms → metabolized for excretion * Tissue uptake of α-tocopherol from VLDL, LDL, and HDL.

Answer 120

* 90% in an unesterified form in fat droplets in adipose tissue → **however**, this is released slowly and does not represent an available source of vitamin E when intakes are low

Answer 121

* Catabolized by the liver * α-tocopherol incorporated into VLDL by α-TTP & released into blood

Answer 122

Excreted in bile (feces) and urine

Answer 123

* Main function = **antioxidant** * Functions in interior of membranes → vitamin E is fat-soluble * Protects membranes from lipid peroxidation * The radical form is not destructive due to the aromatic ring structure stabilizing the charge * **Other** functions, less characterized * Interaction with cell receptors and signalling molecules (e.g., inhibits protein kinase C) * Regulation of gene expression

Answer 124

* **Selenium and vitamin E interaction** * Selenium required for glutathione peroxidase (= enzyme that converts lipid peroxides into lipid alcohols) * Complementary action of both nutrients → therefore, lower intakes of selenium puts higher demands on vitamin E and *_vice versa_*. * **Vitamin C and vitamin E interaction** * Vitamin C regenerates vitamin E after termination of lipid peroxidation step * **Polyunsaturated fatty acids and vitamin E interaction** * Requirement for vitamin E increases/decreases as degree of unsaturation of fatty acids in body tissue rises/falls * Luckily, foods high in PUFA are also relatively good sources of vitamin E. * **Fat-soluble vitamins and vitamin E interaction → A, E, and K (D does not interfere as much)** * Vitamin E inhibits β-carotene absorption and metabolism in the intestine * Vitamin E impairs vitamin K absorption and metabolism.

Answer 125

* Prevalence = rare in adults * **(1) Diseases/conditions that cause fat malabsorption** * Cystic fibrosis * Chronic cholestasis (decreased bile production) * **(2) Genetic defects** * Lipoprotein disorders * α-tocopherol transfer protein (α-TTP)

Answer 126

* **Vitamin E functions to maintain the integrity of cell membranes** * Symptoms: * Fragile red blood cells = **hemolytic anemia** (RBCs lyse due to lack of vitamin E to protect their cell membranes) * Degeneration of nerve cells and effects on muscle = peripheral neuropathy (pain/numbness in extremities); ataxia (poor muscle coordination); skeletal muscle pain; weakness * Skin: ceroid pigments (oxidized proteins and fats) accumulate and appear as brown spots

Answer 127

* Increased tendency for bleeding/impaired blood coagulation (due to impaired vitamin K absorption and RBC lysis) * Gastrointestinal distress including nausea, diarrhea, flatulence

Answer 128

Answer → B The carbon at position 2 is bound to 4 different groups.

Answer 129

* (1) α-tocopherol is the only form of vitamin E maintained in plasma, and the only form that contributes to vitamin E activity * Because of preferential binding to α-tocopherol transfer protein (α-TTP), which is necessary for secretion of vitamin E from the liver * (2) Only 2R-stereoisomers of α-tocopherol appear to have any activity. * 2S-stereoisomers disappear rapidly from blood and do not have significant vitamin E activity. * **(3) Body is unable to interconvert the different forms of vitamin E.**

Answer 130

* Current recommendations → in units of mg alpha-tocopherol * 1mg vitamin E = 1 mg RRR-alpha-tocopherol or 2 mg all rac-alpha-tocopherol * Based on induced deficiency in humans and the correlation between H₂O₂-induced erythrocyte lysis and _plasma alpha-tocopherol concentrations_ * Note * EAR and RDA based on the 2R-stereoisomeric forms of alpha-tocopherol * UL based on all 8 stereoisomeric forms of alpha-tocopherol

Answer 131

**8** RRR, RSR, RSS, RRS, SSS, SSR, SRS, SRR

Answer 132

**4** RRR, RSR, RSS, RRS

Answer 133

Answer → C Vitamin E is mostly found in plant oils. A low fat diet would exclude these sources.

Answer 134

Answer → B We absorb all the different forms, and many forms are deposited throughout the body. Once the chylomicron remnant reaches the liver, other non-biological forms are metabolized and excreted from the body.

Answer 135

* **Initiation** → lipid (PUFA) reacts with *free radical* generating *lipid carbon centered radical* (alkyl radical) * **Propagation** → Alkyl radical reacts with oxygen to form lipid peroxyl radical which then reacts with another lipid to form another alkyl radical → chain reaction continues unless interrupted * **Termination** → vitamin E reduces lipid peroxyl radical and alkyl radical, ending the chain of oxidation * Vitamin E becomes an α-tocopherol radical → regenerated by vitamin C

Answer 136

Regeneration by vitamin C.

Answer 137

Answer → A Higher intakes of PUFA means more UFA inside cells → more prone to oxidation → more vitamin E is necessary to interrupt the chain reaction

Answer 138

False. Vitamin E has a UL = 1,000mg/day Applies to all supplemental forms of alpha-tocopherol * Symptoms of excess * Increased tendency for bleeding/impaired blood coagulation (due to impaired vitamin K absorption and RBC lysis) * Gastrointestinal distress including nausea, diarrhea, flatulence

Answer 139

True. UL = 1,000mg/day * Symptoms of excess: * Increased tendency for bleeding/impaired blood coagulation (due to impaired vitamin K absorption and RBC lysis) * Gastrointestinal distress including nausea, diarrhea, flatulence

Answer 140

Answer → A

Answer 141

* Intakes of RRR-α-tocopherol and other 2R-stereoisomers of α-tocopherol are considered * Other forms, although absorbed, do not contribute to requirements.

Answer 142

Vitamin A = a group of compounds that possess the biological activity of **retinol** (in present form or after conversion) Includes: * **Retinoids** → retinol, retinal, retinoic acid, and retinyl esters * a.k.a. pre-formed vitamin A * **Provitamin A carotenoids** → β-carotene (*highest provitamin A activity*), α-carotene, and β-cryptoxanthin * Carotenoids can be converted to vitamin A. * Note β-carotene is essentially two retinol molecules

Answer 143

RAE = retinol activity equivalent → conversion factor defined for estimation of EAR for vitamin A

Answer 144

* Animal sources → retinyl esters * Beef liver, herring, milk, egg * Plant sources → carotenoids * Spinach, carrots, collards, cantaloupe, sweet potato

Answer 145

* Protein-bound carotenoids and retinyl esters hydrolyzed by pepsin and other proteases → carotenoids and retinyl esters hydrolyzed by hydrolases, esterases, and lipases → free carotenoids and free retinol * Fatty acids, phospholipids. monoacylglycerol, and cholesterol emulsified with bile and incorporated into micelles with free carotenoids and free retinol for absorption via passive diffusion across the brush border membrane.

Answer 146

* Vitamin A → 70-90% absorbed as long as the meal contains some (~10g) fat * Carotenoids → \<5% for carotenoids in uncooked vegetables or non-heat-processed juice; ~60% if present as pure oil or as part of a supplement * Fiber → especially pectin; interferes with micelle formation **(1)** Micelles deliver carotenoids (including beta-carotene) and retinol to the intestinal cell, where they are absorbed by passive diffusion. **(2)** Beta-carotene is converted to 2 retinol **(3)** Retinol (from diet and conversion from beta-carotene) is converted to retinyl ester (storage form of vitamin A) **(4)** Retinyl esters + carotenoids are incorporated into chylomicrons with other lipids and enter the lymphatic and then blood circulation

Answer 147

* **Chylomicrons** enter lymph, then the bloodstream via the thoracic duct and deliver retinyl esters & carotenoids to extrahepatic tissues (i.e., muscle, lungs, adipose tissue) * **Chylomicron remnants** deliver remainder of retinyl esters & carotenoids to the liver

Answer 148

* Once hepatic storage capacity is exceeded, toxicity may occur * Retinol (from diet and conversion from beta-carotene) is converted to retinyl ester (= storage form of vitamin A)

Answer 149

* Retinol and retinal/retinoic acid * Oxidized to various metabolites * Metabolites (water soluble) excreted in urine (60%) * Some metabolites are secreted into bile for fecal excretion (40%)

Answer 150

* Retinol and retinal/retinoic acid * Oxidized to various metabolites * Metabolites (water soluble) excreted in urine (60%) * Some metabolites are secreted into bile for fecal excretion (40%)

Answer 151

1. **Dietary fat** → needed for absorption of vitamin A 2. **Heat** → cooking improves the bioavailability of carotenoids 3. **Fibre** → especially pectin → interferes with micelle formation and absorption 4. **Protein** → needed for converting beta-carotene to retinol and for transport of vitamin A

Answer 152

* Vitamin A, as a fat-soluble vitamin, is transported within cells and in the circulation **bound to proteins** * Circulating form = retinol-RBP-transthretin complex → a.k.a. prealbumin * In cells: * Retinol binds to cellular retinol-binding proteins (CRBPs) * Retinoic acid binds to cellular retinoic acid-binding proteins (CRABPs)

Answer 153

1. **Dietary fat** → needed for absorption of vitamin A 2. **Protein** → needed for converting beta-carotene to retinol and for transport of vitamin A 3. **Vitamin E and vitamin K** → excess vitamin A intake can lower the bioavailability of vitamin E and K.

Answer 154

* Less common in developed countries * Increased risk * Fat malabsorption disorders (e.g., cystic fibrosis, IBD) * Protein deficiency

Answer 155

* Night blindness * Xerophthalmia * Anorexia * Impaired growth * Obstruction and enlargement of hair follicles * Keratinization of epithelial cells (skin) * Increased susceptibility to infections

Answer 156

* **Retinoids** * **Vision** * Roles related to regulation of gene expression: * Cellular differentiation, proliferation and growth * Immune system * Reproduction * Bone development * **Carotenoids** * Potent antioxidant → presence of conjugated double bonds * Eye health * Protects against: * Heart disease * Cancer * Macular degeneration * Cataracts

Answer 157

* Once hepatic storage capacity for retinol is exceeded, toxicity may occur: * **Acute** → GI effect (e.g., nausea), headache * **Chronic** → liver abnormalities; reduced bone mineral density; bone and joint pain * **Teratogenic** → miscarriage; birth defects; permanent learning disabilities * UL = 3000ug preformed vitamin A

Answer 158

Answer → D Vitamin A = a group of compounds that possess the biological activity of **retinol** (in present form or after conversion) Includes: * **Retinoids** → retinol, retinal, retinoic acid, and retinyl esters * **Provitamin A carotenoids** → β-carotene (highest vitamin A activity), α-carotene, and β-cryptoxanthin

Answer 159

Answer → D 5000mcg / (12mcg/RAE) = ~417 2000mcg/ (24mcg/RAE) = ~83 Total = 500 RAE Answer → No

Answer 160

Answer → E

Answer 161

* Add a fat source (e.g., oil) * Add heat (e.g., cook the carrot to help release the vitamin A from the food matrix) * Remove the apple (i.e., the pectin will reduce absorption) * Add a protein source (not necessarily important for absorption, but is important for transport)

Answer 162

1. **Dietary fat** → needed for absorption of vitamin A; low fat = low absorption 2. **Protein** → needed for converting beta-carotene to retinol and for transport of vitamin A; low protein = low transport/utilization

Answer 163

* **Nightblindness** → vitamin A (cis-retinal) is needed for rhodopsin for light detection in rod cells, which are important for ability to see in low light conditions * **Dry, scaly skin** → related to vitamin A's role in cellular differentiation, proliferation, and growth * **Frequent colds** → suppressed immune system and increased susceptibility to infections

Answer 164

Answer → A * Teratogenic toxicity * May lead to miscarriage * Effects on the fetus/child * Birth defects (e.g., cleft palate) * permanent learning disabilities

Answer 165

False. \>700 carotenoids in total, but only 60 are consumed in the diet Examples of non-vitamin A precursor carotenoids: * Lycopene, zeaxanthin, lutein * No vitamin A activity, but may have other important physiological functions

Answer 166

True. \>700 carotenoids in total, but only 60 are consumed in the diet. Examples of non-vitamin A precursor carotenoids: * Lycopene, zeaxanthin, lutein * No vitamin A activity, but may have other important physiological functions

Answer 167

β-carotene → 2 retinal → retinol or retinoic acid * Not all β-carotene converted to retinal → **1 β-carotene does not necessarily = 2 RAL** * Up to 15% of β-carotene escaped cleavage * Non-central cleavage → produces various alcohols and aldehydes

Answer 168

Answer → A

Answer 169

In the liver vitamin A (retinol) is: 1. Used as retinoic acid in regulation of gene expression 2. Stored as retinyl esters 3. Excreted with bile 4. Secreted bound to retinol binding protein (RBP) which joins with transthyretin (TTR) to circulate retinol as a tri-molecular complex

Answer 170

* When vitamin A intake is in excess and serum retinol concentrations increase to levels \> normal range: * Retinol is no longer transported exclusively by RBP * Carried by plasma lipoproteins → **When retinol is presented in this form to the cells, it produces toxic effects**

Answer 171

* **In the liver:** * A small portion → retinol * A portion is incorporated into lipoproteins → extrahepatic tissues * **Transport and tissue uptake through lipoproteins**

Answer 172

1. Light hits retina 2. Rhodopsin molecule is cleaved 3. Signals are sent to the brain (eyesight) 4. Rhodopsin: Opsin + vitamin A (retinal) 5. Vitamin A is needed to make more rhodopsin

Answer 173

False. * Once hepatic storage capacity for retinol is exceeded, toxicity may occur: * **Acute** → GI effect (e.g., nausea), headache * **Chronic** → liver abnormalities; reduced bone mineral density; bone and joint pain * **Teratogenic** → miscarriage; birth defects; permanent learning disabilities * UL = 3000ug preformed vitamin A

Answer 174

True. * Once hepatic storage capacity for retinol is exceeded, toxicity may occur: * **Acute** → GI effect (e.g., nausea), headache * **Chronic** → liver abnormalities; reduced bone mineral density; bone and joint pain * **Teratogenic** → miscarriage; birth defects; permanent learning disabilities * UL = 3000ug preformed vitamin A

Answer 175

Answer → A High intakes can cause orange skin.

Answer 176

Selenium is an **essential micronutrient**, or trace element. * **(1) Inorganic forms** (supplements and some plants) * *selenide*: **Se^2-** (H₂Se or Na₂Se) * *selenite*: Se⁴⁺ (H₂SeO₃ or Na₂SeO₃) * *selenate*: Se⁶⁺ (H₂SeO₄ or Na₂SeO₄) * **(2) Organic forms** (selenoamino acids) * *selenomethionine* (mainly _plants_) * *selenocysteine* (mainly _animals_)

Answer 177

* Essential role in several important metabolic pathways, through **selenoproteins (\>25)** with **selenocysteine** at the active site * **(1) Glutathione (GSH) peroxidase** → antioxidant enzyme which neutralizes hydrogen peroxide and other peroxides * **(2) Thyroid hormone metabolism** → iodothyronin 5'-diodinase (ID); important in converting different forms of thyroid hormone; inactive thyroxine (T₄) to active form thyronine (T₃) * **(3) Antioxidant** → selenoprotein P → antioxidant function: major selenium-containing protein in blood for selenium transport

Answer 178

* (1) Poor growth * (2) Muscle pain and weakness → selenoprotein-N * (3) Whitening of nail beds * **(4) Keshan's Disease** * Cardiomyopathy due to coxsackie virus * Low selenium increases susceptibility * **(5) Kashin-Beck's disease** * Osteoarthropathy = degeneration and necrosis of the joints and epiphyseal-plate cartilage * Low selenium plays a role (with other factors)

Answer 179

* Brazil nuts, seafood, meats, whole grains → soil selenium concentrations vary greatly; therefore, selenium content in food varies * **Forms** in food and supplements: * _Mainly in organic form_ * Plants and supplements: * *Seleno**_methionine_*** * *Inorganic forms* * Animal products: * *Seleno**_cysteine_***

Answer 180

* Selenium may help prevent some toxic effects associated with some metals, e.g., arsenic-associated skin lesions

Answer 181

* Possible role in disease prevention due to its antioxidant function * Some epidemiological evidence to suggest a beneficial effect → suggested to reduce the risk of cancer and cardiovascular disease, but overall limited evidence. * In contrast, higher selenium concentrations in some studies associated with increased risk for diabetes, hypertension, and some cancers * Excess intake of selenium has adverse effects; small range between deficiency and excess.

Answer 182

* UL for selenium = 400ug/day for adults * **No regulation on selenium absorption** * High intakes = high uptakes; therefore, toxicity possible

Answer 183

* Chronic toxicity/chronic selenosis: * Hair and nail brittleness and loss = critical endpoint on which to base a UL * GI disturbances * Skin rash * **Garlic breath odour** due to excretion in breath * Nervous system abnormalities * More likely from supplements than food forms of selenium.

Answer 184

* Atherosclerosis * Cancer * Eye disease * Autoimmune diseases * Lung damage

Answer 185

Answer → C Most of what we eat are organic forms of selenium (selenocysteine and selenomethionine) are absorbed by amino acid transporters. Less commonly consumed forms: Selenate via active diffusion and selinite via passive diffusion

Answer 186

Based on depletion-repletion studies and on studies estimating obligatory losses of selenium over a range of intake allowed Note: A single brazil nut provides more than the RDA.

Answer 187

Answer → C No right answer, some studies are leaning towards B, and some evidence suggests C.

Answer 188

Answer → D

Answer 189

Answer → B

Answer 190

* **Observational studies (cannot prove causal relationships)** → higher consumption vegetables and fruits: lower risks of several diseases, including CVD, stroke, cancer, and cataracts * **Animal models** → antioxidants interacted with free radicals and stabilized them, thus preventing the free radicals from causing cell damage → *can these results be translated to human metabolism?* * **9 RCTs** of dietary antioxidant supplements for cancer prevention worldwide → no evidence they are beneficial * **1 systematic review** → available evidence regarding use of vitamin and mineral supplements for chronic disease prevention

Answer 191

* Other factors in food * Different dosage compared to foods * Differences in the chemical composition of antioxidants in foods vs supplements * 8 forms of vitamin E in food but only alpha-tocopherol used in most studies * Duration of antioxidant supplement use → not long enough to prevent chronic diseases

Answer 192

* Evidence for a benefit of antioxidant supplements in **limited** and **mixed**. * In general, it seems **better to get antioxidants through a healthy diet** than through supplements. * If you are considering a dietary supplement, first get information on it from **reliable sources**. High dose supplements (especially single nutrient supplements) may increase risk for some diseases and may interact with medications or other supplements.

Answer 193

* ‘Internal framework’ of body * Enable movement * Protects the brain, heart, and other internal organs * Mineral storage (e.g., calcium and phosphorus)

Answer 194

* **Bone growth** → occurs during stages of growth * Fetal development and infancy * Childhood * Adolescence * **Bone modelling** → forms shape of bones; bone is dynamic tissue

Answer 195

* Bone resorption and rebuilding → occurs throughout life * Osteoclasts → bone resorbing cells → dissolve bone * Osteo**b**lasts → bone **building** cells → build new bone

Answer 196

* Childhood/adolescence → net bone growth * Early to middle years of adulthood → no net change * 35-40 years or older → net bone loss * Note: Women lose bone mass faster than men due to menopause which reduces estrogen

Answer 197

* Osteoporosis → reduced total bone mass (density); ‘porous’ * **Risk factors** * _Non-modifiable_ * Estrogen deficiency → menopause reduces estrogen significantly * Ethnicity * Family history * _Modifiable_ * Deficiency of vitamin D, calcium, phosphorus, magnesium * Physical inactivity * Excess alcohol * Smoking

Answer 198

* Osteomalacia → inadequate mineralization of bone (i.e., soft bones) → in children = rickets * **Risk factors:** * Inadequate dietary calcium intake * Insufficient calcium absorption due to vitamin D deficiency * Phosphate deficiency caused by increased renal losses * **Mechanism = Vitamin D deficiency** * Decreased calcium absorption and decreased serum calcium * Decreased calcium for bone mineralization * Decreased phosphorus absorption * As bone turnover occurs, the **bone matrix is preserved** while **bone mineralization is impaired**

Answer 199

* Vitamin D = **calciferol**; a.k.a. the sunshine vitamin * Two main forms: * Ergocalciferol, **D₂** → synthesized in plants * Cholecalciferol, **D₃** → synthesized in animals * Differ only in side chains * Both can be converted to the active form and have the same metabolic activity * Active form = **1,25-(OH)₂-D** (calcitriol)

Answer 200

* Food sources → fatty fish, liver, shitake mushrooms, fortified products (milk, orange juice) * Forms in food → D₃ (animals); D₂ (plants) * Forms in supplements/fortified foods → both

Answer 201

No digestion required

Answer 202

* Where → mostly jejunum * How: * Absorbed in micelles by passive diffusion * Incorporated into chylomicrons in enterocyte * Chylomicrons → lymph → blood → liver → vitamin D to extrahepatic tissues * Chylomicron remnants → remaining vitamin D to the liver

Answer 203

* **Calcidiol (25(OH)D)** = main circulating form in blood * Tightly bound to vitamin D binding protein * Half life = 2-3 weeks * Biomarker for vitamin D status assessment * Target: uptake by tissues (mainly kidney) for conversion to active hormone form, calcitriol * **Calcitriol (25(OH)₂D)** * Loosely bound to vitamin D binding protein (facilitates tissue uptake) * Shorter half-life than calcidiol = 2-6 hours only * Acts in target tissues: * Bone, intestine, kidney * Also, heart, muscle, pancreas, and central nervous system

Answer 204

* Other metabolites of vitamin D

Answer 205

* Calcitroic acid is the major excretory product * Conjugation and excretion via the bile

Answer 206

* Vitamin D₃ (cholecalciferol) synthesized from **7-dehydrocholesterol** in skin upon exposure to UVB

Answer 207

* Lumisterol and tachysterol → lost as skin cells are sloughed → prevents over production → cannot get toxic levels from sun exposure! * Endogenous synthesis is dependent on: * Sunblocks and sunscreen use * Skin pigment (lower synthesis with darker skin) * Aging (vitamin D synthesis decreases with age) * Time of day * Season & latitude → angle of the sun in the winter months in Canada is such that you _cannot_ synthesize enough even with sun exposure.

Answer 208

* **Liver** (***25-hydroxlyase***): Vitamin D → 25(OH)D (calcidiol) * Most vitamin D in liver → converted to calcidiol and secreted into blood * **Calcidiol transport** * Calcidiol = major circulating form in blood * Tightly bound to vitamin D binding protein (DBP) * Half life = 2-3 weeks * Biomarker for vitamin D status assessment * Target = uptake by tissues (mainly kidney) for conversion to the active hormone form of vitamin D, **1,25(OH)₂D** (mainly in kidney) * **Kidney (1****α-hydroxylase):** Calcidiol → 1,25(OH)₂D (calcitriol) * _Regulated process_ → stimulated by parathyroid hormone (PTH) → occurs with low calcium levels * **Transport of calcitriol** * Loosely bound to DBP (facilitates tissue uptake) * Shorter half-life than calcidiol → 2-6 hours only * Acts on target tissues * Bone, intestine, kidney * Also, heart, muscle, pancreas, central nervous system.

Answer 209

**Most commonly used indicator = serum 25(OH)D (calcidiol) concentration** → strong correlation with dietary vitamin D intake

Answer 210

1. Genomic action → regulation of gene expression (\>200 genes) 2. Non-genomic action → activation of signal transduction pathways; physiological responses

Answer 211

* Insufficient exposure to sunlight with inadequate dietary intake * Limited time outside, use of sun protection (clothing, sunscreen), higher latitudes * Fat malabsorption and inadequate endogenous synthesis * At risk populations: * Older adults → typically have lower intake and lower synthesis * Breastfed infants → human milk is low in vitamin D, infants most protected from sun exposure

Answer 212

* **Rickets in infants and children** * A disorder of failed bone mineralization * Defective mineralization of cartilage and the epiphyseal growth plate * Bowing of legs with weight-bearing * **Osteomalacia in adults** * Impaired bone remineralization = ‘softening’ of bones * Prolonged elevation of blood PTH

Answer 213

* Hypercalcemia; hyperphosphatemia * Calcification of soft tissues * Impaired renal function

Answer 214

* Depending on criteria used, up to 75% of people may have suboptimal vitamin D status * Current recommendation is 15 mcg (600IU) * Endocrine society suggests that 50mcg (2000IU) per day may be needed to raise low levels * Bottom line → when possible, aim to get ~15 mins of sun exposure 2-3x per week for vitamin D synthesis * When this is not possible (winter months), take a supplement with 15-50mcg (600-2000IU)

Answer 215

* 0.025 mcg = 1 IU * 15 mcg = 600 IU * 25 mcg = 1000 IU

Answer 216

False. Vitamin D has an RDA.

Answer 217

True. For me = 15 mcg/day = 600 IU

Answer 218

Answer → D Fat soluble vitamins → A, D, E, and K; absorption enhanced by dietary fats

Answer 219

* Notice from the graphs that darker skin requires longer exposure for the same amount of synthesis → trade-off → those with darker skin also have less DNA damage from UVB exposure because melanin is protective * For European white skin → estimated that ~15 minutes of sun exposure is needed on arms and legs during peak sun hours 2-3 times per week (Hollick, 2014).

Answer 220

Answer → D Everyone in Canada requires a Vitamin D supplement in the winter months.

Answer 221

* Bone * Intestine * Kidney * Heart * Muscle * Pancreas * Central Nervous System

Answer 222

Answer → B

Answer 223

* Regulation of \>200 genes * Vitamin D binds to vitamin D receptor (VDR) * VDR/RXR complex * Vitamin D response element * Enhanced gene expression * Increased expression of proteins needed to maintain calcium homeostasis * Promotes **differentiation** of white blood cells, intestinal epithelial cells and osteoclasts * Promotes **proliferation** of fibroblasts and keratinocytes

Answer 224

* Via binding to vitamin D receptor on cell membranes * Activation of signal transduction pathways * Physiological responses * May be important for: * Calcium absorption * Regulation of calcium channels in muscle

Answer 225

* Via genomic and non-genomic action → increases blood Ca * Low blood calcium → stimulates PTH release * PTH stimulates 1,25(OH)₂D synthesis in kidney * Increased 1,25(OH)₂D and PTH leads to [3]: * Increased calcium reabsorption in **kidney** * Increased **intestinal** absorption of calcium and phosphorus * Increased resorption of calcium and phosphorus from **bone** * **Net result = Increased blood calcium**

Answer 226

1. **Calcium and phosphorus** → uptake and serum levels regulated by vitamin D 2. **Dietary lipids (fatty acids)** → improve absorption of vitamin D

Answer 227

Answer → C

Answer 228

* **Vitamin D deficiency** * Decreased calcium absorption and decreased serum calcium * Decreased calcium for bone mineralization * Decreased phosphorus absorption * As bone turnover occurs, the **bone matrix is preserved** while **bone mineralization is impaired**

Answer 229

False. UL = 4000 IU for adults * Symptoms of excess: * Hypercalcemia * Calcification of soft tissues * Impaired renal function

Answer 230

True. UL = 4000 IU * Symptoms of excess: * Hypercalcemia * Calcification of soft tissues * Impaired renal function

Answer 231

Answer → E Vegans → many sources are non-vegan Older adult females → lower synthesis and lower intakes This could be extended to everyone in winter months in higher latitudes.

Answer 232

**Natural food sources** → dairy products; some seafood (e.g., salmon); nuts; legumes and legume products (especially tofu); some vegetables **Form of calcium in foods** → insoluble calcium salts **Form of calcium in supplements →** calcium carbonate, calcium citrate, and other salts (note; calcium carbonate requires acidity for digestion/absorption, so it is advised to take with food since food stimulates HCl production; this is not the case for calcium citrate)

Answer 233

* Conversion of insoluble calcium salts to free Ca²⁺ (in the acidic stomach environment of the stomach via HCl)

Answer 234

* **Saturable, carrier-mediated, active transport** * Carrier = TRPV6 (a.k.a. calcium transporter 1, CaT1) * Upregulated by calcitriol; decreases with age * Occurs in duodenum and proximal jejunum * **Paracellular diffusion** → passive, nonsaturable, _nonregulated_ process * Dose dependent * Occurs in jejunum and ileum

Answer 235

* Absorption rate is **highest in infants** and young children (60%) * Absorption rate is **lowest in older adults** and women with low estrogen (15-20%); because [3]: * Calcium transporter expression decreases with age * Endogenous synthesis of vitamin D (required for calcium homeostasis/absorption) * Decreased stomach acidity (required for calcium digestion/absorption)

Answer 236

* Hormones that regulate serum calcium concentration include: * PTH * Calcitriol * Calcitonin

Answer 237

1. Bone mineralization 2. Activator of muscle contraction 3. Cofactor in blood clotting → calcium needed for blood clotting factors 4. Signal transduction (Secondary messenger Ca²⁺) 5. Stimulation of enzyme activity (calmodulin) 6. Nerve transmission

Answer 238

* **Absorption enhancers** * Vitamin D * Sugars and sugar alcohols * Protein * **Absorption inhibitors** * Fibre * Phytic acid * Oxaclic acid * Excessive divalent cations (Zn and Mg) * Unabsorbed fatty acids * **Urinary excretion enhancers:** * Sodium * Protein * Caffeine * Calcium impairs phosphorus, iron and fatty acids.

Answer 239

* **Absorption enhancers** * Vitamin D * Sugars and sugar alcohols * Protein * **Absorption inhibitors** * Fibre * Phytic acid * Oxaclic acid * Excessive divalent cations (Zn²⁺ and Mg²⁺) * Unabsorbed fatty acids * **Urinary excretion enhancers:** * Sodium * Protein * Caffeine * Calcium impairs phosphorus, iron and fatty acids.

Answer 240

* Alcohol use * Corticosteroid use * Calcium low * Estrogen low * Smoking * Sedentary lifestyle * **Populations at risk** → adolescents and older adults in Canada due to low dietary intake; vitamin D inadequacy

Answer 241

* **Osteoporosis** → reduced total bone mass (density) * **Neuromuscular impairment** * Increase neuromuscular excitability * Intermittent contractions of muscle that fail to relax * Hand and feet muscles most affected * **Tetany** * Characterized by continuous severe muscle spasms * Can cause respiratory dysfunction and death

Answer 242

* **Hypercalcemia** → lethargy; anorexia; nausea; vomiting; heart arrhythmias; higher risk for kidney stones * Causes * Usually from high dose supplements (or antacids) * Hyperparathyroidsm

Answer 243

RDA → established based on the amount required for bone health and to maintain adequate retention

Answer 244

Answer → C 100g of spinach contains ~135mg calcium

Answer 245

Answer → A 125mg x 32% = 40mg (milk) 50mg x 61% = 30mg (broccoli) 115mg x 5.1% = 7mg (spinach)

Answer 246

* Binding to **calbindin** * Shuttle across the cytosol * Release near basolateral membrane

Answer 247

Ca²⁺-ATPase pump

Answer 248

* Same as in circulating blood * (1) Bound to protein, mainly albumin (40-45%) * (2) Complexed with sulfate, phosphate, citrate, and/or bicarbonate (up to 10%) * (3) Free Ca²⁺ (45-50%)

Answer 249

* Excreted through urine and feces * Fecal excretion = what was not absorbed * Urinary excretion is regulated; **98% is reabsorbed**

Answer 250

* **Protein** → however; overall small effect on Ca balance because while high protein increases Ca excretion in the urine, high protein intake also increases calcium intestinal absorption (= no net effect) * **Caffeine** → small losses (2-3mg Ca/cup of coffee) * **Na⁺**→ share common reabsorption mechanism; higher Na⁺ intake = increased Calcium excretion

Answer 251

Answer → C

Answer 252

Answer → A Hormones which increase serum calcium: **PTH** **1,25-(OH)₂-D** *Note: Calcidiol is the inactive form of vitamin D in the blood.*

Answer 253

Answer → C **Intestine** → increases absorption **Bone** → promotes resorption (i.e., release of calcium from bone) **Kidney** → reabsorb more to keep it in the blood **Thyroid gland** → vitamin D does not target this endocrine organ

Answer 254

* (1) **PTH** released by parathyroid gland in response to low circulating calcium levels * (2) In **kidney** * PTH stimulates activation of calcidiol to calcitriol * PTH and calcitriol **increase renal reabsorption** of filtered calcium * (3) In **small intestine** * **Calcitriol** **enhances intestinal calcium absorption** through increased transcription of (1) calbindin, (2) TRPV6, and (3) Ca²⁺-ATPase pumps * (4) In **bone** * PTH and calcitriol stimulate osteoclasts which promote **release of calcium from bone** into blood * (5) Once serum calcium levels are adequate, secretion and actions of PTH and calcitriol are suppressed

Answer 255

* High [Ca] stimulates release of **calcitonin** from the thyroid * **Suppresses PTH** production and release * **Inhibits osteoclast activity** → blocks calcium and phosphate release from bone * **Promotes bone mineralization** * Inhibits renal reabsorption of calcium and phosphate → **enhanced urinary losses** of calcium and phosphate * Eventually brings serum Ca back to the normal range

Answer 256

* **To increase intracellular Ca²⁺** → activation of cell membrane channels allowing its entry; Ca²⁺ released from organelles * **To lower intracellular Ca²⁺** → release from cells via ATPase pumps; sequestered in organelles

Answer 257

Answer → B Tightly controlled mechanisms exist to keep serum and cellular calcium levels within a very narrow range, (at the expensive of bone calcium).

Answer 258

* Lack of satisfactory test to measure calcium status on a routine basis. * **(1) Serum/plasma calcium (not effective due to tightly controlled regulation mechanisms)** * So tightly regulated that it doesn't reflect dietary intake or biochemical status * Measurement of disturbances in calcium metabolism * **(2) Non-invasive techniques to assess bone mineral density (more reliable methods)** * DEXA scan * CT scan

Answer 259

Answer → D Calcium is needed for blood clotting factors, which are vitamin K dependent GLA-proteins. Calcium is needed for bone mineralization; one of the vitamin K dependent proteins is **osteocalcin (a GLA-protein)** which helps to bind calcium and bring it into bone → important for bone mineralization

Answer 260

Across the lifespan → not just in older adults or high-risk periods for osteoporosis; because → higher peak bone mass = more bone to lose before developing osteoporosis

Answer 261

False. **Hypercalcemia** → lethargy; anorexia; nausea; vomiting; heart arrhythmias; higher risk for kidney stones

Answer 262

True. **Hypercalcemia** → lethargy; anorexia; nausea; vomiting; heart arrhythmias; higher risk for kidney stones

Answer 263

* Low calcium intake/status has been associated with an increased risk of * Hypertension * Colon cancer * Type 2 diabetes * Obesity * Causal relationship not confirmed to date

Answer 264

Answer → E A → symptoms of excess; however Jane is not exceeding the UL

Answer 265

* Second most abundant mineral in the body * 85% in bone and teeth * 1% in ECF * 14% associated with soft tissues * Occurs in the body in form of inorganic phosphate (P_i) and organic phosphates (bound to protein, saccharides, or lipids (e.g., phospholipids))

Answer 266

1. Structural component of bone 2. Component of multiple biological molecules (DNA; RNA; ATP; phospholipids; coenzyme forms of vitamins) 3. Regulation of enzyme function (glycogen phosphorylase; glycogen synthase) 4. Acid-base balance 5. Oxygen delivery (RBCs)

Answer 267

* **Natural food sources** → meat; poultry; fish; eggs; dairy; nuts; legumes; grains; widely distributed in foods; phosphates in additives and colas * **Forms in foods** → mostly organic forms in meats (phospholipids; phosphorylated proteins and saccharides); inorganic phosphates * In grains → phytic acid = not bioavailable

Answer 268

* Hydrolysis of organic phosphate compounds by phosphatases * Phospholipase C * Alkaline phosphatase on brush border

Answer 269

* Where → throughout small intestine * How → as free inorganic phosphate ion * (1) paracellular diffusion (main) * (2) Sodium-dependent, saturable, carrier-mediated, active transport; enhanced by 1,25-(OH)₂-D * Efficiency varies (50-80%); higher for animal sources * Absorption _not_ affected by body P status * High intakes * High serum P levels * Increased urinary excretion

Answer 270

* Excretion through urine and feces * Urinary excretion = primary means of excreting phosphate and maintaining phosphate homeostasis * Excreted as inorganic phosphate ion * Reabsorbed with low-normal intakes * High serum phosphate promotes urinary phosphate excretion * **Regulated by PTH and FGF23** → both promote excretion by diminishing reabsorption

Answer 271

* **Inhibitors** * **Magnesium** → formation of non-bioavailable complex * Calcium containing **antacids** (Ca acetate or carbonate → bind phosphorus

Answer 272

* Serum phosphate concentration are regulated but not as tightly as calcium * Hormones involved in P regulation: * (1) Fibroblast growth factor (FGF) 23 * (2) PTH → released by parathyroid gland * (3) Calcitriol * (1) and (2) inhibit P reabsorption in kidneys

Answer 273

* Rare, only seen in cases of: * Severe malnutrition * Other conditions such as hyperparathyroidism

Answer 274

* Impaired bone health: rickets; osteomalacia; bone pain * Skeletal muscle weakness and cardiomyopathy

Answer 275

* **Causes** * Excessive intakes from food additives and colas * Renal disease → impaired excretion of phosphates * Vitamin D toxicity * **Diagnostics** * high serum phosphate (hyperphosphatemia) * **Symptoms** * Calcification of non-skeletal tissues * Increased risk for atherosclerosis and heart disease

Answer 276

* Thiamin diphosphate (TDP) * Pyridoxal 5'-phosphate (PLP) * Flavin mononucleotide (FMN) * Flavin adenine dinucleotide (FAD) * Nicotinamide adenine dinucleotide (NADH) * Nicotinaminde adenine dinucleotide phosphate (NADPH) * Coenzyme A (CoA)

Answer 277

Answer → E

Answer 278

* RDA based on balance studies

Answer 279

Answer → E Phosphorus is widely distributed in food, so deficiency due to inadequate intake is unlikely.

Answer 280

Answer → B

Answer 281

Answer → C

Answer 282

Answer → D Decreased renal function leads to impaired urinary excretion.

Answer 283

* **Enhancers [3]** * Protein intake → improves solubility * Presence of lactose and sugar alcohols → improves solubility * Gastric acidity * **Inhibitors [6]** * Oxalic acid (spinach, rhubarb, swiss chard) → binds calcium and forms insoluble complex * Phytic acid (whole-grain breads, seeds, legumes) → binds calcium and forms insoluble complex * Magnesium, zinc → compete with calcium for absorption * Fibre → binds calcium so that it is not absorbed * Unabsorbed fatty acids → bind calcium and form calcium soaps that are not absorbed; mostly a concern for those with fat malabsorption disorders (e.g., liver disease, pancreatic disorders, cystic fibrosis, etc.)

Answer 284

* **Enhancers [3]** * Protein intake → improves solubility * Presence of lactose and sugar alcohols → improves solubility * Gastric acidity * Vitamin D → enhances expression of calcium transporters

Answer 285

* **Inhibitors [6]** * Oxalic acid (spinach, rhubarb, swiss chard) → binds calcium and forms insoluble complex * Phytic acid (whole-grain breads, seeds, legumes) → binds calcium and forms insoluble complex * Magnesium & zinc → compete with calcium for absorption * Fibre → binds calcium so that it is not absorbed * Unabsorbed fatty acids → bind calcium and form calcium soaps that are not absorbed; mostly a concern for those with fat malabsorption disorders (e.g., liver disease, pancreatic disorders, cystic fibrosis, etc.)

Answer 286

* Bone mineralization/ structural component * Enzymatic reactions * Ion channel regulation (K and Ca channels) * Enhances insulin release and action * And more!

Answer 287

None required

Answer 288

* **Where** → small intestine * **How** → in Mg²⁺ form * **(1) Saturable, carrier-mediated, active transport via TRPM6** → inhibited by high cytosolic Mg concentration * **(2) Paracellular diffusion (main mechanism at high intakes)** → increases as Mg concentration in lumen increases

Answer 289

* Transport in blood, including hepatic portal vein * (1) Free Mg2+ (50-55%) = physiologically active form * (2) Bound to protein, mainly albumin (20-30%) * (3) Complexed with sulfate, phosphate, and citrate (5-15%)

Answer 290

Excretion mainly through kidney → excretion is regulated, 95-97% is reabsorbed.

Answer 291

* **Enhancers** → protein & carbohydrates; high doses of vitamin D (enhances paracellular uptake) * **Inhibitors** * Phytic acid (whole-grain breads, seeds, legumes) * Fibre * Unabsorbed fatty acids (in case of fat malabsorption; form soaps with Mg) * Phosphorus (forming non-bioavailable complex Mg₃(PO₄)₂.

Answer 292

* **Excretion affected by** * Plasma Mg concentration * PTH * **Factors promoting Mg urinary excretion:** * Diuretic medications * Protein * Alcohol * Caffeine

Answer 293

* Low intakes → common * Low intake of whole plant foods

Answer 294

* **Non-specific symptoms** → delayed diagnosis * Fatigue, lethargy, weakness, nausea, vomiting * **Diagnostics** * Plasma/serum magnesium concentration * Routinely measured indicator, but not sensitive and cutoff is debated

Answer 295

* Possible increased risk of * Hypertension * Type 2 diabetes * Possible role of Mg: * Sleep * Leg cramps * Migraines * Depression and anxiety

Answer 296

* Excessive magnesium from food sources does not cause toxicity, due to efficient renal excretion. * Excessive intake possible from high-dose supplements. * **Symptoms** * Diarrhea * Nausea, vomiting * Muscle weakness, paralysis

Answer 297

→ 50-60% of total body Mg is in bone → together with calcium and phosphorus → forms bone crystal lattice

Answer 298

**Structural cofactor to stabilize enzyme or allosteric activator** → assists in stabilization of ATP and transfer of phosphate group * Enzymatic roles including in glucose, fat, protein, and nucleic acid metabolism

Answer 299

**K and Ca Channels** * Mg is a ‘natural calcium channel blocker’ and also activates calcium ATPase → decreased intracellular calcium * Mg is needed for Na/K+ pump and maintaining K+ concentration in cells * Relevant for (1) nerve conduction, (2) muscle contraction, and (3) heart rhythm.

Answer 300

Answer → E

Answer 301

* Natural food sources → nuts, seeds, whole grains, legumes, green leafy vegetables, seafood, dairy * **Form in foods** → Mg²⁺ * **Forms in supplements** → Mg-citrate, Mg-gluconate, Mg-lactate

Answer 302

RDA → established based on magnesium balance studies. 320mg/day for me!

Answer 303

Answer → D

Answer 304

Via Na+-ATPase pump

Answer 305

Homeostasis is regulated at **intestinal absorption** and **urinary excretion**. * **Vitamin D** enhances intestinal absorption of all three minerals: its main function is to increase calcium transporters to enhance calcium absorption, but it can also increase paracellular absorption of Mg and P at high levels as well. * **Vitamin D and PTH** stimulate bone resorption so all three minerals are released. * **Vitamin D** enhances renal reabsorption of calcium and phosphate, but not magnesium. * **PTH** enhances renal reabsorption of calcium and magnesium, but inhibits the renal reabsorption of phosphate (i.e., enhances urinary excretion). * Calcium and phosphate can form an insoluble, inactive complex (calcium phosphate), so excreting more phosphate in urine when PTH levels are high can help to prevent this. * **FGF23** is released from bones when phosphate levels are high and inhibits renal reabsorption of phosphate and inhibits activation of vitamin D → acts to decrease phosphate levels. * **Calcitonin** is released when calcium levels are high. It inhibits bone resorption to decrease calcium levels.

Answer 306

Answer → A Vitamin D enhances the expression of calcium transporters; vitamin D is critical for calcium absorption. High doses of vitamin D enhance paracellular uptake of magnesium.

Answer 307

* PTH enhances renal reabsorption (decrease urinary excretion) * PTH activates vitamin D; vitamin D enhances absorption of magnesium * PTH acts with vitamin D to increase bone resorption (minerals are released from bone, including magnesium) * Net effect = increased serum magnesium levels

Answer 308

* Mg transporters are inhibited; less is absorbed * Magnesium itself inhibits renal reabsorption (urinary excretion increased) * Net effect = decrease serum magnesium

Answer 309

Answer → A * PTH enhances renal reabsorption (decrease urinary excretion) * PTH activates vitamin D; vitamin D enhances absorption of magnesium * PTH acts with vitamin D to increase bone resorption (minerals are released from bone, including magnesium) * Net effect = increased serum magnesium levels

Answer 310

High Mg inhibits P absorption → with increasing Mg intake → decreasing P absorption due to formation of Mg₃(PO₄)₂

Answer 311

Low Mg²⁺ associated with low K⁺ Low [Mg²⁺] → increasing K⁺ efflux from cells and subsequent renal K⁺ excretion

Answer 312

* (1) **Low** Mg associated with hypocalcemia → Mg²⁺ cofactor for 25-hydroxylase which activates vitamin D * (2) **Excess** Mg interferes with calcium function * Mg²⁺ reduces Ca²⁺ flux across membranes and activates Ca2+-ATPase pumps → reduces intracellular [Ca²⁺]. * Mg²⁺ competes with Ca²⁺ for binding sites on troponin C and myosin → alters muscle contraction

Answer 313

Answer → A * Low magnesium → low calcitriol because the active form of vitamin D requires two hydroxylation steps, one of which requires magnesium * Low magnesium is associated with low calcium through vitamin D * Low magnesium disrupts the sodium-potassium pump and lets potassium be excreted out

Answer 314

Answer → C

Answer 315

Answer → B

Answer 316

Answer → B Vitamin D increases serum phosphate by increasing absorption (lesser effect than compared to calcium); increases renal absorption (countered by PTH which decreases renal absorption); enhance resorption from bone.

Answer 317

Answer → A

Answer 318

Answer → C PTH secreted when calcium levels are low → acts to increase absorption, mostly through vitamin D; renal reabsorption and bone resorption

Answer 319

Answer → B PTH does increase bone resorption; but inhibits renal reabsorption → no net effect on serum P

Answer 320

Answer → A

Answer 321

* **Main function = formation of thyroid hormones** * Triiodothryonine (T₃) → 3 iodide * Thyroxine (T₄) → 4 iodide * Thyroid hormone production and secretion → regulated by thyroid-stimulating hormone (TSH, also called thyrotropin) * TSH will result in an enlarged thyroid gland if iodide is deficient.

Answer 322

* **Food** → mostly animal sources → seafood; **seaweed**; dairy; smaller amounts in meats, grains & legumes * Iodide content in plant and animal foods varies by region because soil iodide content greatly varies → **Canada has low levels of iodide in soil** * **Salt fortification** in Canada → added to all table salts

Answer 323

* Pre 1920's **goiter** (enlarged thyroid due to iodine deficiency) was **common in Canada** due to low consumption/availability of iodine rich food sources * Iodine added to all table salts in Canada → **¼ tsp provides ~90μg iodide** * Kosher, pickling, and sea salt → contains natural iodine, but not as much as iodized table salt.

Answer 324

None required for free, ionic forms (iodide I^-)

Answer 325

Rapid absorption mostly in stomach

Answer 326

* Free iodide in blood * Highest uptake by thyroid glands through _active transport_ * Thyroid gland synthesizes and secretes thyroid hormones → **70-80% of total body iodide in thyroid gland as thyroid hormones**

Answer 327

* **Selenium, iron & vitamin A deficiency** can enhance the effect of iodine deficiency → needed for iodide uptake and synthesis of thyroid hormones * **Goitrogens (i.e., known to increase risk of goiter)** → glucosinolates in cabbage, kale, cauliflower, Goitrin in cassava → **impaired uptake of iodide into thyroid gland**

Answer 328

* **Urinary iodine concentration → main biomarker** * Changes with diet * Indicator for mild/moderate/severe deficiency but also of excess iodine status * **Thyroid gland → indirect indicator** * Physiologic indicator of gland health * Enlargement of the thyroid gland in case of deficiency * **Serum TSH concentration** * Increased concentration of thyroid-stimulating hormone in blood = indicator for potential iodine deficiency

Answer 329

* **Risk factors** → areas without iodide fortification, especially if farther away from the ocean * **Deficiency** → Goiter (swelling of thyroid gland) * In pregnancy → congenital iodine deficiency = impaired physical and intellectual development; stillbirths and spontaneous abortions * Maternal iodine deficiency during pregnancy is associated with impaired cognitive development in offspring → **the effect of iodine deficiency in the first half of pregnancy is irreversible.**

Answer 330

Most people are very tolerant to excess intake; excess status is not likely due to efficient urinary excretion. Iodine does still have a UL.

Answer 331

* Thyroiditis (inflammation of thyroid gland) * Goiter * Hypothyroidism or hyperthyroidism * Thyroid papillary cancer * **UL for iodine = 1100ug/day**

Answer 332

Answer → B Fatigue, weight-gain, and high TSH are associated with iodine deficiency.

Answer 333

RDA defined by studies quantifying the thyroid iodine accumulation and turnover rates

Answer 334

Answer → E

Answer 335

* Absorbed unchanged (i.e., T₃ and T₄) * Allows thyroid hormone medication to be administered orally

Answer 336

* **Urinary excretion (80-90%)** * Kidneys have no reabsorption or other mechanism to control urinary iodide excretion * Excess dietary iodine that was absorbed into the blood stream but not taken up by tissues or thyroid glands is directly excreted * **Urinary excretion fluctuates with recent dietary intake**

Answer 337

Answer → A * Kidneys have no reabsorption or other mechanism to control urinary iodide excretion * Excess dietary iodine that was absorbed into the blood stream but not taken up by tissues or thyroid glands is directly excreted. * Urinary excretion fluctuates with recent dietary intake.

Answer 338

* **Inadequacy** results in reproducible structural and/or physiological abnormalities or speicific biochemical changes. * **Adequacy** can prevent abnormalities; sometimes, supplementation can reverse abnormalities

Answer 339

* **Adipose tissue** → enhances lipolysis * **Muscle** → enhances contraction * **Bone** → promotes anabolism (growth and development) * **Cardiovascular system** → increases heart rate * **GI tract** → stimulates nutrient digestion and absorption * **Metabolism** → stimulates metabolic rate and cellular oxygen consumption in metabolically active tissues

Answer 340

The science is unclear. Takeaway → depends on what else people are eating; how much they are restricting salt; where the live in relation to the ocean & iodine rich soil If you are trying to reduce sodium → reduce highly processed foods; continue to use table salt

Answer 341

Vitamins A, D, E, C, B6, B3, and choline.

Answer 342

False. Dehydroascorbic acid is absorbed via GLUT transporters and then reduced to ascorbic acid within the enterocyte via glutathione reductase.

Answer 343

False. Fatigue in scurvy is due to decreased carnitine synthesis.

Answer 344

False. Ruptured blood vessels occur due to decreased collagen synthesis.

Answer 345

False. Bruising is due to decreased collagen synthesis.

Answer 346

Component of metalloenzymes (gustin)

Answer 347

False. Zinc absorption decreases

Answer 348

False. Zinc absorption is increased at low pH (high acidity).

Answer 349

False. Phytic acid inhibits absorption of zinc.

Answer 350

Copper and vitamin C

Answer 351

* The higher doses of antioxidants in supplements can have harmful effects (e.g., beta-carotene increases risk of lung-cancer in smokers) * It is difficult to trace the origin of chronic diseases to a set time or cause * The form of antioxidants in supplements may not be the same as the beneficial form in foods. * Foods contain other components that may have beneficial effects on health.

Answer 352

False. The main form is retinol bound to RBP and transthyretin.

Answer 353

False. The main form is retinol bound to RBP and transthyretin.

Answer 354

False. The main form of vitamin A transported in systemic circulation is retinol bound to retinol binding protein and transthyretin.

Answer 355

False. The main form is retinol bound to RBP and transthyretin.

Answer 356

High calcium concentrations are sensed primarily by the **thyroid**, which then secretes **calcitonin** to reduce plasma calcium.

Answer 357

There is a slightly increased risk of heart disease with calcium supplements, but if her health provider suggests she needs a supplement the benefits of taking it probably outweigh the risks.

Answer 358

Take the supplement with a meal including fat to enhance absorption.

Answer 359

False. Most is absorbed as free inorganic phosphate ions.

Answer 360

False. Most is absorbed as free inorganic phosphate ions.

Answer 361

False. Most is absorbed as free inorganic phosphate ions.

Answer 362

False. It is fortified with cholecalciferol.

Answer 363

False. It is fortified with cholecalciferol.

Answer 364

False. It is fortified with cholecalciferol.

Answer 365

False. It is fortified with cholecalciferol.

Answer 366

Phosphorus

Answer 367

There is a reduction in vitamin D formation in the skin with increasing age.

Answer 368

Organic phosphate

Answer 369

* Chemical structure * Dietary sources * They have the same function

Answer 370

False. It reflects both endogenous synthesis and exogenous intake of vitamin D.

Answer 371

False. It reflects both endogenous synthesis and exogenous intake of vitamin D.

Answer 372

False. It reflects both endogenous synthesis and exogenous intake of vitamin D.

Answer 373

False. Calcitriol is the functional form. Calcidiol (the main circulating form) reflects both endogenous synthesis and exogenous intake of vitamin D.

Answer 374

PTH activates vitamin D which enhances intestinal absorption and bone resorption of Ca, P and Mg. Calcium and phosphate can form an insoluble, inactive complex (calcium phosphate), so excreting more phosphate in urine when PTH levels are high can help to prevent this.

Answer 375

True. Insulin response and glucose tolerance → signalling and release; impaired glucose tolerance in zinc deficiency

Answer 376

False. **Insulin response and glucose tolerance** → signalling and release; impaired glucose tolerance in **zinc deficiency**

Answer 377

* **Neuromuscular impairment** * Increase neuromuscular excitability * Basically calcium prevents rapid depolarization caused by sodium entering the cell (down its electrochemical gradient). So less calcium, quicker depolarization. * Intermittent contractions of muscle that fail to relax * Hand and feet muscles most affected

Answer 378

* **Tetany** * Characterized by continuous severe muscle spasms * Can cause respiratory dysfunction and death

Answer 379

**Saturable, carrier-mediated, active transport of Mg via TRPM6** → inhibited by high cytosolic Mg concentration

Answer 380

* Carnitine transports long-chain fatty acids into the mitochondria so they can be oxidized ("burned") to produce energy. * It also transports the toxic compounds generated out of the mitochondria to prevent their accumulation.

Answer 381

False. * Lumisterol and tachysterol → lost as skin cells are sloughed → prevents over production → cannot get toxic levels from sun exposure!

Answer 382

True. * Lumisterol and tachysterol → lost as skin cells are sloughed → prevents over production → cannot get toxic levels from sun exposure!

Answer 383

False. * Excessive magnesium from food sources does not cause toxicity, due to **efficient renal excretion**. * Excessive intake possible from high-dose supplements. * **Symptoms** * Diarrhea * Nausea, vomiting * Muscle weakness, paralysis

Answer 384

True. * Excessive magnesium from food sources does not cause toxicity, due to efficient renal excretion. * Excessive intake possible from high-dose supplements. * **Symptoms** * Diarrhea * Nausea, vomiting * Muscle weakness, paralysis

Answer 385

True. * Excessive magnesium from food sources does not cause toxicity, due to efficient renal excretion. * Excessive intake possible from high-dose supplements. * **Symptoms** * Diarrhea * Nausea, vomiting * Muscle weakness, paralysis

Answer 386

False. * Excessive magnesium from food sources does not cause toxicity, due to efficient renal excretion. * Excessive intake possible from high-dose supplements. * **Symptoms** * Diarrhea * Nausea, vomiting * Muscle weakness, paralysis

Answer 387

False. * Absorption _not_ affected by body P status * High intakes lead to: * High serum P levels * Increased urinary excretion

Answer 388

True. * Absorption _not_ affected by body P status * High intakes lead to: * High serum P levels * Increased urinary excretion

Answer 389

False. Digestion of zinc requires release from proteins and nucleic acids.

Answer 390

False. Digestion of zinc requires release from proteins and nucleic acids.

Answer 391

False. Digestion of zinc requires release from proteins and nucleic acids.

Answer 392

False. However, one of the metabolic functions of calcium is stimulation of enzyme activity, including calmodulin.

Answer 393

*cis*-Retinal

Answer 394

True. Tyrosinase → copper containing metalloenzyme which synthesizes melanin.

Answer 395

True. Some of these hormones include gastrin, cholecystokinin, vasopressin, and calcitonin.

Answer 396

True. Cu/Zn superoxide dismutase.

Answer 397

False. alpha-tocopherol is the most active form of vitamin E because alpha-tocopherol transfer protein preferentially **secretes** vitamin E from the liver.

Answer 398

False. alpha-tocopherol is the most active form of vitamin E because alpha-tocopherol transfer protein preferentially secretes vitamin E from the liver.

Answer 399

False. alpha-tocopherol is the most active form of vitamin E because alpha-tocopherol transfer protein preferentially secretes vitamin E from the liver.

Answer 400

False. alpha-tocopherol is the most active form of vitamin E because alpha-tocopherol transfer protein preferentially secretes vitamin E from the liver.

Answer 401

False. Menke's disease leads to deficiency of copper due to decreased release of copper from enterocytes through ATP7A.

Answer 402

False. Menke's disease leads to deficiency of copper due to decreased release of copper from enterocytes through ATP7A.

Answer 403

False. Menke's disease leads to deficiency of copper due to decreased release of copper from enterocytes through ATP7A.

Answer 404

False. Menke's disease leads to deficiency of copper due to decreased release of copper from enterocytes through ATP7A.

Answer 405

False. Vitamin C is needed to reduce copper to the active Cu⁺ form.

Answer 406

False. Vitamin C is needed to reduce copper to the active Cu⁺ form.

Answer 407

False. Vitamin C is needed to reduce copper to the active Cu⁺ form.

Answer 408

False. Copper absorption mainly occurs through carrier mediated absorption that is reduced at high intakes of copper.

Answer 409

False. Copper absorption mainly occurs through carrier mediated absorption that is reduced at high intakes of copper.

Answer 410

False. Paracellular diffusion occurs at high intakes. Copper absorption mainly occurs through carrier mediated absorption that is reduced at high intakes of copper.

Answer 411

False. Phosphorus absorption primarily occurs through non-saturable passive paracellular diffusion.

Answer 412

False. Phosphorus absorption primarily occurs through non-saturable passive paracellular diffusion.

Answer 413

False. Phosphorus absorption primarily occurs through non-saturable passive paracellular diffusion.

Answer 414

False. Copper is excreted primarily through feces.

Answer 415

False. Copper is excreted primarily through feces.

Answer 416

* **Keshan** → selenium deficiency increases susceptibility of cardiomyopathy due to coxsackie virus * **Kashin Beck** → selenium deficiency plays a role; osteoarthropathy

Answer 417

False. The main effect of copper toxicity is liver damage.

Answer 418

False. The main effect of copper toxicity is liver damage.

Answer 419

False. The main effect of copper toxicity is liver damage.

Answer 420

False. The main effect of copper toxicity is liver damage.

Answer 421

False, animal products are only a good source of retinoids.

Answer 422

Inorganic phosphates and organic phosphates (bound to DNA, proteins, etc.)

Answer 423

Metabolism of vitamin C to oxalic acid for excretion in urine.

Answer 424

False. Vitamin C absorption is down-regulated at high intakes.

Answer 425

Cholecalciferol, D3

Answer 426

Ergocalciferol, D2

Answer 427

Conjugated double bonds

Answer 428

No, because serum calcium levels are tightly regulated.

Answer 429

Calcium supplements should be taken at separate times from **iron** supplements because of potential interactions inhibiting absorption.

Answer 430

Phosphorus deficiency is rare, but is more likely to occur among individuals **with hyperparathyroidism or severe malnutrition**.

Answer 431

False. Phosphorus toxicity is more likely to occur in individuals with renal failure.

Answer 432

False. Phosphorus toxicity is more likely to occur in individuals with renal failure.

Answer 433

False. Phosphorus toxicity is more likely to occur in individuals with renal failure.

Answer 434

False. Wilson's disease is associated with increased storage of copper in the liver.

Answer 435

False. Wilson's disease is associated with increased storage of copper in the liver.

Answer 436

False. Wilson's disease is associated with increased storage of copper in the liver.

Answer 437

False. Wilson's disease is associated with increased storage of copper in the liver.

Answer 438

Reduced activation of vitamin D

Answer 439

Calcium Vitamin D

Answer 440

Low iodine stimulates release of TSH which increases thyroid growth.

Answer 441

Irreversible impaired cognitive development in offspring.

Answer 442

* **Iron** → high zinc may reduce iron absorption * **Calcium** → high zinc may interfere with calcium absorption * **Copper** → high zinc increases metallothionein which may ‘trap’ copper in the enterocyte and reduce its absorption

Answer 443

* Suppression of immune system * Copper deficiency * Anemia

Answer 444

No, current evidence suggests that taking a zinc supplement does not appear to reduce the risk of getting a cold.

Answer 445

Evidence suggests that taking vitamin C will not reduce the incidence of common colds, but may decrease the duration and severity of a cold.

Answer 446

**Selenium** → cofactor for glutathione peroxidase **Copper** → cofactor for Cu/Zn superoxide dismutase **Zinc** → structural component of Cu/Zn superoxide dismutase **Vitamin E** → termination of lipid peroxidation chain reaction **Vitamin C** → reduction of alpha-tocopherol radical (oxidized vitamin E)

Answer 447

**1. Cu and Zn both required for Cu/Zn superoxide dismutase** **2. Vit C needed for regeneration of oxidized vitamin E** **3. Se and vitamin E both needed for prevention/reducing damage from lipid peroxidation** → Vitamin E can donate an electron + hydrogen to an LOO• radical, forming LOOH, and glutathione peroxidase converts this lipid peroxide to a lipid alcohol (LOH). So vitamin E and glutathione peroxidase work together to eliminate free radicals that form in cell membrane lipids.

Answer 448

Vitamin A as retinoic acid is important in regulating gene expression for cell proliferation and differentiation (important for growth and development) as well as the immune system.

Answer 449

Vitamin A is stored in the liver, and therefore, higher doses every few months can be taken to fill liver stores, which can be released during times when intakes are lower.

Answer 450

Retinol can be obtained from preformed vitamin A (retinoids) or some carotenoids. RAE accounts for the conversion of carotenoids to retinol and their different contributions to total retinol activity in the body.

Answer 451

Vitamin A is a fat-soluble vitamin that is absorbed with dietary fats; therefore, taking vitamin A with dietary fat will improve its absorption.

Answer 452

* When calcium is low, PTH is released from the parathyroid. * In the kidney, PTH promotes activation of vitamin D to calcitriol. * Calcitriol enhances calcium and phosphate (to some extent) absorption from intestine. * PTH and calcitriol increase resorption of calcium and phosphate from bone * Calcitriol increases reabsorption of calcium and phosphate from the kidney * PTH increases calcium reabsorption but inhibits phosphate resorption in kidney * The net effect of calcitriol is to increase both calcium and phosphate in serum * PTH increases calcium but has no net effect on phosphate levels.

Answer 453

Calcitonin - released from thyroid gland

Answer 454

FGF23 – released from bone (osteocytes)

Answer 455

Intracellular calcium levels are maintained through a balance of calcium entry into the cell (via calcium channels) and release from the cell (via transporters), as well as regulated storage and release of calcium from organelles.

Answer 456

* Calcium carbonate requires acidity for digestion/absorption, so it is advised to take with food since food stimulates HCl production. * This is not the case for calcium citrate.

Answer 457

Less commonly consumed forms: **Selenate** via active transport **Selinite** via passive diffusion

Answer 458

Mg-citrate Mg-gluconate Mg-lactate

Answer 459

All-racemic α-tocopherol (i.e., all possible stereoisomers of α-tocopherol) α-tocopheryl acetate α-tocopheryl succinate

Answer 460

Zinc salts (e.g., zinc sulfate, zinc gluconate)

Answer 461

Copper sulfate and other complexed forms

Answer 462

Ascorbic acid Calcium ascorbate Sodium ascorbate Dehydroascorbate

Answer 463

* **Inorganic forms:** * *selenide*: **Se^2-** (H₂Se or Na₂Se) * *selenite*: **Se⁴⁺** (H₂SeO₃ or Na₂SeO₃) * *selenate*: **Se⁶⁺** (H₂SeO₄ or Na₂SeO₄) * **Organic form → selenomethionine**

Answer 464

Ergocalciferol, D2 Cholecalciferol, D3

Answer 465

Calcium carbonate Calcium citrate …and other salts

Final Exam Material Flashcards

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