Nutrition III: Vitamins & Minerals

Question 1

Describe deficiency symptoms for major water-soluble vitamins:

1. Thiamin
2. Niacin
3. Folic Acid (3)
4. Vitamin B12 (3)
5. Vitamin C

Answer 1

1. Thiamin -
   beriberi: cardiac failure, peripheral & central neuropathies
2. Niacin - Pellegra –> photosensitive dermitis
3. Folic acid
   - megaloblastic anemia***
   - leucopenia
   - thrombopenia
4. Vitamin B12
   - Megaloblastic anemia,
   - hyperhomocysteinemia
   - pernicious anemia
5. Vitamin C - scurvy

Question 2

Explain potential etiologies of pernicious anemia.

Answer 2

Result of a lack of Intrinsic Factor.

Lack of intrinsic factor may result from autoantibodies produced against the protein or congenital form of impaired intrinsic factor secretion.

Question 3

Describe toxicity syndrome for Niacin and Vitamin C.

Answer 3

1. Niacin
   - flushing of skin, pruritus, nausea & vomiting
2. Vitamin C
   - kidney stones in susceptible persons

Question 4

Describe the inter-relationship between folate and vitamin B 12

What accumulates if there is a deficiency in vitamin B12?

Answer 4

Methyl Trap Hypothesis

• both folate & vitamin B12 are required for synthesis of thymidilate (using thymidilate synthesis to make dTMP - precursor)
• folate is necessary for purine and thymidilate synthesis
• a major source of folate for body tissues is THF
• reduction of methylene THF to methyl THF is irreversible (METHYL TRAP)
• only role of METHYL THF is methylation of homocysteine to methionine
• only way methyl THF to get demethylated back to THF is through methionine synthase activity, WHICH REQUIRES B12!!!
• B12 is defficient, methyl THF accumulates in the cell and THF decreases

aka DNA SYNTHESIS

Question 5

What are the enzymes that are dependent on Folate/ B12 Synthesis? (4)

Answer 5

Dihydrofolate reductase

Thymidylate synthetase

Methylene THF reductase

Methionine synthase
(AKA homocysteine methyltransferase)

Question 6

What are 2 examples of nutrient drug interactions involving folic acid?

Answer 6

1. Methotrexate - inhibits dihydrofolate reductase enzyme
   - enzyme is necessary to remove toxic dihydrofolate and transform it into tetrahydrofolate
2. 5-fluorouracil - inhibits thymidilate synthase enzyme
   - prevents the change from dUMP to dTMP

Question 7

Describe the major role of the following minerals & trace elements:

1. Calcium
2. Phosphorus
3. Iron
4. Iodine

Answer 7

1. Calcium
   - component of hydroxyapatite
   - activation of catalytic properties of proteins
   - stabilization of proteases & blot clothing proteins
   - intracellular signal transduction
2. Phosphorus
   - major component of hydroaxyapetite
   - component of cell membranes
   - second messenger systems
   - energy storage
   - regulation of acid base balance
3. Iron
   - component of TCA cycle enzymes & oxidative phosphorylation
   - heme containing proteins
   - cofactor in oxygen atom transfer
4. Iodine
   - component of thyroid hormones

Question 8

The following describes what mineral:

• component of hydroxyapatite
• activation of catalytic properties of proteins
• stabilization of proteases & blot clothing proteins
• intracellular signal transduction

Answer 8

1. Calcium

Question 9

The following describes what mineral:

• major component of hydroaxyapetite
• component of cell membranes
• second messenger systems
• energy storage
• regulation of acid base balance

Answer 9

2. Phosphorous

Question 10

The following describes what mineral:

• component of TCA cycle enzymes & oxidative phosphorylation
• heme containing proteins
• cofactor in oxygen atom transfer

Answer 10

3. Iron

Question 11

The following describes what mineral:

• component of thyroid hormones

Answer 11

Iodine!

Question 12

What factors induce calcium absorption?(4)

What factors inhibit calcium absorption? (5)

Answer 12

What factors induce calcium absorption?

1. Vitamin D adequacy
2. Calcium deficiency
3. Pregnancy
4. Postweaning status & mucosal permeability

What factors inhibit calcium absorption?

1. Vitamin D deficiency
2. Menopause
3. Decreased stomach acid
4. rapid intestinal trans time
5. Estrogen deficiency (also includes drug induced - Ex: tamoxifen)

Question 13

Explain the etiology of REFEEDING syndrome.

1. What stimulates anaerobic glycolysis?
2. What shifts into cells? How does serum values of this change?
3. What patients is this a particular concern for?

Answer 13

1. Anaerobic glycolysis stimulated by infusion of hypertonic glucose
2. causes rapid shift of PHOSPHOROUS & depleting serum Phosphorous
3. ADP levels may be depleted, and impair multiple Phosphorous requiring processes
4. Particularly a concern in cachectic patients

Symptoms of Refeeding syndrome: sever hyperglycemia, weakness, muscle paralysis, cardiorespiratory failure, death!

Question 14

What is the effect of chronic Phosphorous deficiency?

Answer 14

growth impairment, osteomalacia, myopathy, RBC AND WBC dysfunction, platelet disorders, metabolic acidosis, NS dysfunction

Question 15

Define the roles of the following Iron Proteins (state whether transport or storage and where) AND WHICH TYPE OF IRON (Fe2+ or Fe3+)

1. Ferritin
2. Transferrin
3. Hemosiderin
4. Ceruloplasmin

Which is the storage protein in HEPATOCYTES?
Which oxidizes ferrous to ferric ion for binding to transferrin?

Answer 15

1. Ferritin (binds Fe2+)
   - storage protein in most cells
2. Transferrin (binds Fe3+)
   - transfer protein
3. Hemosiderin
   - storage protein in HEPATOCYTES
4. Ceruloplasmin
   - circulating protein oxidizes ferrous to ferric ion for binding to transferrin (2+ to 3+)

Question 16

1. Describe the deficiency and toxicity of Calcium

2. Describe the deficiency and toxicity of Phosphorous

Answer 16

Calcium:
1. Deficiency: osteoporosis, Toxicity: RARE

Phosphorous:
Deficiency: REFEEDING SYNDROME**, secondary to malabsorption syndromes, vitamin D deficiency, HYPERPARATHYROIDISM,

Toxicity: secondary to advanced renal diseases, hypoparathyroidism

Question 17

1. Describe the deficiency and toxicity of Iron

2. Describe the deficiency and toxicity of Iodine.

Answer 17

Iron:
Deficiency - microcytic hypochromic anemia***** TEST

Toxicity: severe vomiting, diarrhea, abdominal pain, hereditary hemochromatosis

Iodine:
deficiency - endemic goiter, severe deficiency may result in endemic cretinism

Toxicity: GOITER

Question 18

The following describes the main function of what Vitamin:

1. NAD & NADP coeznymes for redox reactions, ATP synthesis, ADP ribose transfer reactions
2. Dietary tryptophan metabolized to NAD (60mg Tryptophan = 1 mg Niacin)

Answer 18

NIACIN

Question 19

Which mineral is associated with the 4D’s (PELLAGRA)?

What are they?

Answer 19

NIACIN

1. Diarrhea
2. Dermatosis - on exposed skin, NOT FACE usually (casual’s necklace)
3. Dementia
4. Death

Similar to Pellegra –> Hartnup’s syndrome –> characterized by impaired synthesis of niacin from tryptophan resulting in Pellagra-like symptoms

Question 20

Niacin deficiency is similar to a thiamin deficiency often seen in alcoholics, a disease called __________

What is Niacin often used for?

Answer 20

Wiernecke’s - Encephalopathy

Used as an antihyperlipidemic agent –> decreases triglyceride levels by inhibiting adenylate cyclase activity thereby lowering VLDL synthesis

Question 21

What are the functions of:

1. Folate
2. B12

How is Folic Acid Status assessed?

Inhibition of which step in the purine and thymidilate synthesis pathway results in megaloblastic anemia? By What?

Answer 21

1. Folate
   * coenzyme in methyl group reactions*
   - purine and pyrimidine synthesis
   - methylation of tRNA
2. B12
   - coenzyme for methionine synthase (homocysteine methyl transferase)
   AND methylmalonyl - CoA Mutase (converts methylmalonylCo A to succinyl Co A)
3. Plasma 5-methyl THF
4. Inhibition of THYMIDILATE SYNTHASE (with 5-flurouracil = cancer drug)
   - by FOLATE or B12 deficiency

Question 22

How are levels of B12 assessed?

Where is this released initially?

Where is vitamin B 12 found?

Answer 22

1. Plasma Cobalamin B12 levels
2. Released from foods by gastric pepsin

• Vitamin B 12 is made by bacteria, present in all forms of ANIMAL tissue
• NOT IN PLANTS

cobalamin = the bomb because its for meat eaters only (and I’m the bomb ok)

Question 23

Deficiency in B12 results in inhibition of _____ _____.

Leading to impaired synthesis of ____

and an increase in ______

WHICH RESULTS IN _______ ANEMIA?

Answer 23

1. Methionine Synthase
2. DNA
3. Plasma Homocysteine
   - elevated homocysteine levels in blood = risk factor for vascular disease
4. MEGALOBLASTIC ANEMIA

Question 24

The following describe which Vitamin:

1. Essential for cross linking of collagen
2. NT and Neuropeptide synthesis of corticosteroids and aldosterone in the adrenal cortex
3. Hydroxylation of tryptophan to form SEROTONIN in the brain
4. Antioxidant in aqeuous phase, scavenges hydroxyl, peroxyl, and superoxide radicals, regenerates active form of Vitamin E

Answer 24

1. Collagen

Question 25

How are plasma vitamin C levels assessed? What is an early sign of this deficiency?

Answer 25

Plasma and leukocyte concentrations - Bleeding of the gingiva

Question 26

How do the levels of the following change with HYPOCALCEMIA: 1. Plasma Calcium levels 2. PTH levels. Activation of Vitamin D results in what 3 changes?

Answer 26

1. DECREASE 2. Increase a) increased reabsorption from proximal tubule b) increased intestinal absorption c) increased bone RESORPTION

Question 27

What are two ways that calcium is absorbed? What is a potent inhibitor of calcium absorption?

Answer 27

ACTIVE: calcium enters calcium channel, binds to calbindin, transported across cytosol, released into circulation via Ca-ATPase & Na/Ca exchanger PASSIVE - between intestinal cells along calcium gradient Potent inhibitor = Oxalic Acid (forms indigestible salt) & PHYTATE (plant storage form of phosphorous) - high protein diets increase calcium excretion (via antiproton in kidney cells) CALCIUM status --> plasma or ECF

Question 28

The renal handling of Phosphorous: 1. Kidneys: reabsorbed in ______ _____ with Na 2. MAIN REGULATORS (name 3) 3. How does PTH affect phosphorous reabsorption?

Answer 28

1. Proximal Tubule 2. GFR, Tubular Reabsorption, PTH 3. PTH DECREASES Phosphorous reabsorption - hyper P increases clearance - hypo P, decreases clearance ASSESS BY SERUM PHOSPHOROUS LEVELS

Question 29

The following describe what syndrome: (state the cause & associated drops in what other ions) 1. Occurs when severely malnourished, dehydrated individuals given glucose & saline 2. Results from rapid expansion of extracellular fluid (↑ sodium intake) & increased insulin secretion (↑ carbohydrate intake) 3. Stimulates rapid glycogen synthesis, depleting plasma phosphorus concentration

Answer 29

REFEEDING SYNDROME May result in cardiac arrhythmias and sudden death Not caused solely by rapid drop in plasma phosphorus levels, also potassium, magnesium & vitamins

Question 30

Iron is found in 2 oxidation states: Fe2+ and Fe3+ Which is bound to transferring for plasma transport? Which is required for absorption from the gut, cellular storage in Ferritin, and synthesis of heme? In iron deficiency what is unregulated and what is down regulated (TfR/Ferritin) Iron excess?

Answer 30

1. Fe3+ 2. Fe2+ 3. Tfr is UPREGULATED in deficiency (increase receptor on cell surface) Ferritin is DOWNREGULATED = released opposite for excess --> ferritin increased for storage, and down regulation of Tar

Question 31

The iron sulfur complex is part of mitochondrial ______, an enzyme that catalyzes the conversion of CITRATE to ISOCITRATE in the citric acid cycle. - critical for cellular energy production

Answer 31

ACONITASE

Question 32

Microcyic Hypochromic Anemia is associated with a deficiency in ________

Answer 32

Iron - this occurs because without sufficient iron, hemoglobin synthesis is inhibited (ALA DEHYDRATES STEP) - thereby allowing additional cell division resulting in smaller RBC's - fatigue, lightheadedness, dyspnea upon exertion, difficult swallowing (lump in throat) , sore mouth and tongue

Question 33

What are 3 important functions of heme containing proteins?

Answer 33

1. Carries oxygen in hemoglobin and myoglobin 2. Constituent of peroxidase enzymes & protects cells from oxidative injury 3. Heme iron serves as active site for cytochromes

Question 34

What is the diagnosis for iron deficiency: Serum Ferritin _____, followed by a _____ in serum iron. Iron Binding Capacity _____ and transferring saturation is ______.

Answer 34

FALLS - decrease in serum Iron - Iron Binding capacity INCREASES - transferrin saturation is LOW ** efficiency of iron absorption INCREASES in deficiency***