Water Soluble Vitamins

Question 1

vitamins

• definition
• sources

Answer 1

organic molecules required to maintian normal growth, devpt, metabolism

• synthesized by gut bacteria: K, biotin
• synthesized from precursors
  
  • cholesterol → vit D
  • Trp → niacin
• dietary intake essential to meet required amts

Question 2

vitamins involved in blood formation/clotting

Answer 2

vit B-6

vit B-12

folate

vit K

Question 3

vitamins involved in protein/aa metabolism

Answer 3

vit B-6

vit B12

folate

vit C

choline (not true vitamin)

riboflavin (indirect)

Question 4

vitamins involved in antioxidant defenses

Answer 4

vit E

vit C

carotenoids

riboflavin (indirect)

Question 5

vitamins involved in gene expression

Answer 5

vit A

vit D

Question 6

vitamins involved in bone health

Answer 6

vit A

vit D

vit K

vit C

Question 7

vitamins involved in energy metabolism

Answer 7

thiamin

riboflavin

niacin

pantothenic acid

biotin

vit B-12

Question 8

vitamins vs carbs/fats/proteins

Answer 8

• both organic

differences

• no calories
• micronutrients
• not present in large quantities in food

Question 9

bioavailability and factors that affect it

Answer 9

amount of a nutrient that is actually absorbed and used by body (vs. amt ingested)

• efficiency of digestion/transit time in GI tract
  
  • acid production necessary to release B12 from protein to which it is bound
  • diarrhea decreases transit time/abs
• method of food prep
• nutrient source (natural vs synthetic/fortified)
• previous/simultaneous nutrient consumption

Question 10

general process of digestion/abs of water-soluble vitamins (and exceptions)

Answer 10

1. digestive enzymes/low pH in stomach: hydrolysis of vitamins from bound protein complexes
2. upper part of small intestine: absorption
   * vit B12 absorbed in ileum

​3. bloodstream: distributed throughout body

• vit B12 stored
  4. kidneys: excreted rapidly (i.e. body has ltd stores of water-soluble vitamins - should be consumed daily)
• vit B12 stored
• vit B6 (pyridoxine) stored

Question 11

water-soluble vitamins vs fat-soluble vitamins

Answer 11

1. transport

• fat-soluble vits are stored in chylomicrons, released into lymphatic system, then circulated in blood
• water-soluble vits are released directly into blood and travel free

2. storage

• fat-soluble vits are stored in liver and adipose tissue
• water-soluble vits arent stored for most part

3. excretion/toxicitiy

• water-soluble vit excesses are monitored and removed by kidneys
• fat-soluble vitamins are stored, excreted less readily → can develop toxicities more quickly

*vits K and B12 have unique props and so tend not to follow the general rules

Question 12

primary fx of B vitamins

cofactors vs. coenzymes vs prosthetic groups

Answer 12

• B vitamins mostly function as components of coenzymes
• cofactors: accessory molecultes important for protein/enzyme fx
  • either organic (coenzymes) or inorganic (minerals)
  • coenzymes can either by co-substrates (ex. NAD, NADPH) or prosthetic grups (ex. B12, FAD, heme)

Question 13

B vitamin mnemonic

Answer 13

the rhythm nearly proved fully contagious

thiamine = B1

riboflavin = B2

niacin = B3

pyridoxine = B6

folate = B9

cobalamin = B12

Question 14

B1

• name
• sources
• absorption

Answer 14

thiamine

• sources: whole grain food (significant; fortified cereals), other nutritious food (sunflower seeds, tuna)
• absorption
  
  • needs to be phosphorylated to be active (thiamin pyrophosphate)
  • abs reduced in presence of alcohol
  • abs reduced with folate deficiency
  • found in tissues with high metabolic rate: sk muscle, liver, heart, kidneys, brain

Question 15

B1 function

Answer 15

• function
  
  • energy production: helps convert carbs into energy
  • used as a coenzyme with
    
    • pyruvate dehydrogenase
    • alpha-ketoglutarate dehydrogenase
    • branched chain alpha-ketoacid dehydrogenase (BCK-DH)
    • LIV a.a. metabolism
    • transketolase (HMP pathway)
  • evidence of thiamine-binding proteins thathave roles in nervous system (regulation of nt release?)

Question 16

B1 deficiency and toxicity

Answer 16

• deficiency
  
  • ​often seen in alcoholics (poor abs, increased excretion in urine; Wernicke Korsakoff syndrome), malnourished/homeless, extreme diets
  • symptoms: poor appetite, irritability, apathy, confusion, weight loss
  • advanced: beri beri (wet-CV system, dry-neurologic system)
• toxicity
  
  • ​none reported

Question 17

beri beri

Answer 17

• B1/thiamine deficiency
• dry
  
  • muscle waiting, puan, numbness/tingling of lower extremities, difficulty walking
  • in alcoholics, can progress to Wernicke-Korsakoff syndrome: encephalopathy and psychosis
• wet
  
  • abnormalities in cardiovasc system leading to edema

Question 18

B2

• name
• sources
• absorption

Answer 18

riboflavin

• sources: milk/milk products, whole grains [+enriched/fortified grains], liver
  
  • sensitive to UV light/irradiation, stable to heat
• absorption
  
  • circulate bound to albumin or other serum proteins
  • converted to active forms FMN (flavin mononucleotide) and FAD (flavin adenine dinucleotide) in cell

Question 19

B2 function

Answer 19

• prosthetic groups for enzymes
  
  • FAD, FADH2
• involved in redox reactions (oxphos, glutathione reductase for removing ROS)

Question 20

B2 deficiency and toxicity

Answer 20

• deficiency
  
  • ​inflammation of membranes (also occurs with some other B deficits)
    
    • cheilosis: cracks at corners of mouth
    • glossitis: infl of tongue
    • stomatisis: infl of mouth/lips, sensitivity to light
    • seborrheic dermatiti: infl skin condition - flaky white/yellow scales on oily areas (scalp, face, inner ear)
  • bloodshot eyes, sensitivity to bright light
• toxicity
  
  • ​none reported

Question 21

B3

• name
• sources
• forms/absorption

Answer 21

niacin

• sources: protein rich foods (meat, fish, poultry, PB), mushrooms, asparagus, fortified foods
• absorption
  
  • ​found as nicotinic acid, nicotinamide (major form that circulates in blood)
  • active forms: NAD, NADP (from nicotinic acid, nicotinamide, or Trp)

Question 22

B3 function

Answer 22

• redox reactions (NAD, NADP) - over 200 rxns
  
  • production and breakdown of glucose, fats, a.a.s, nucletides

Question 23

B3 deficiency and toxicity

Answer 23

• deficiency seen in alcoholics, corn-based diets without other sources of B3
• pellagra (“rough skin”)
  
  • initially: fatigue, loss of appetite, weakness, anxiety, irritability, depression, GI probs
  • 4Ds
    
    • diarrhea
    • dermatitis
    • dementia
    • death
• toxicity
  
  • ​occurs in supplementation, like when taken for lowering LDL/triacylglycerol and picking up HDL
    
    • niacin sometimes cheap alt for statins
  • get niacin flush and itching (treated with low dose aspirin or ibuprofen)

Question 24

B6

• name
• sources
• absorption

Answer 24

pyridoxine

• sources: protein rich roods (poultry, meat, fish), starchy vegetables, non citrus fruits
• absorption
  
  • ​found as pyridoxal (found mostly in animal products), pyridoxine and pyridoxamine (found ostly in plants)
  • all are converted to PLP (pyridoxal phosphate, a coenzyme - key for a.a. metabolism)

Question 25

B6 function

Answer 25

• transamination reactions (moving amino groups from a.a. to keto acids)​
• deamination reactions
  
  • ​amino acid metabolism
  • urea metabolism
• conversion of Trp to niacin
  
  • implication: B6 deficiency can lead to B3 deficiency!
• neurotransmitter synthesis (serotonin, dopamine, norepi, histamine)
• heme synthesis (pyridoxine is coenzyme for ALA synthase in committed step)

Question 26

B6 deficiency and toxicity

Answer 26

• deficiency is rare, only in some cases
  
  • newborns fed formula low in B6
  • women taking oral contraceptives
  • alcoholics
  • can be consequence of drug interactions
    
    • isoniazid (used to treat TB) binds to B6, induces deficiency
    • penicillamine (used to treat rheumatoid arthritis) depletes pyridoxine → deficiency
  • symptoms: cheliosis, glossitis, pellagra-like dermatitis, depression, confusion (note overlap with B3 symptoms! think B6 fx)
• toxicity
  
  • used pharmacologically to treat carpal tunnel, PMS, asthma, depression, pregnancy nausea, diabetic neuropathy
  • HOWEVER, high doses can lead to irreversible nerve damage (sensory damage, difficulty walking, numbness of hands/feet)

Question 27

B9

• name
• sources
• forms
• absorption

Answer 27

folate [NOT REFERRED TO BY # (B9)]

• codependent with cbalamin (B12)
• sources: dark leafy vegetables (spinach, broccoli, legumes, cirtus fruits), liver, fortified bread/cereal (via folic acid)
• forms/absorption
  
  • ​unlike other B vitamins, many active forms
  • basic structure: ring structure (pteridine) - PABA bridge molecule (para-aminobenzoic acid) - glutamate
  • usually have multiple glutamates at end of chain (aka polyglutamates)
    
    • additional Glu are removed in intestine (until only one left) and methyl group is added: methyltetrahydrofolate which is released in circ and delivered to cells
    • in cells, methylterrahydrofolate is inactive, must be converted to active form

Question 28

how are folates converted from inactive form (methyltetrahydrofolate) to active form in cells?

Answer 28

vitamin B12!!!

• B12 knocks the methyl off of methyltetrahydrofolate, attaches it to itself
  
  • B6 - methyl = activated
  • B12 + methyl = activated
  • both are now ready for their roles in synthesis

Question 29

B9/folate function

Answer 29

• role in synthesis of DNA, RNA, some a.a.s
  
  • esp important in rapidly dividing cells (RBCs, epithelial cells, embryonic cells)
• regen of Met from homoCys

Question 30

B9/folate deficiency: reasons, main signs

link between B9/B12 deficiency

Answer 30

• deficiency due to increased demand (during preg), inadequate absorption (Celiac, Crohn’s), antifolates (ex. methotrexate - leukemia treatment), aldoholism, antacids (hinder abs by increasing pH of upper int)
  
  • ​macrocytic anemia
    
    • ​weakness, fatigue, headache, palpitations, SOB
• tx? supplement BUT **WARNING**
  
  • ​folate supp can reverse anemia, but might mask symptoms of a B12 deficiency - might think you’re getting better and still have neuro damage
  • either give folic acid + B12 or methylmalonic acid test (accumulation = B12 def)

Question 31

folate and birth defects

Answer 31

• folate deficiency associated with neural tube defects
  
  • spina bifida (neural tube not fully closed)
  • anencephaly (brain/skull underdeveloped)
• folate supplementation advised for women planning to be pregnant (folic acid before/during pregnancy)

Question 32

folate and heart disease

Answer 32

• homocysteine is an independent risk factor for atherosclerosis
  
  • increased homoCys due to folate deficiency can be a marker for increased risk of CVD
• smokers might benefit from folic acid supplementation → reduced risk of stroke

Question 33

B9/folate toxicity

Answer 33

excessive consumption of folic acid as supplement could mask a potential B12 deficiency

• would take care of expected anemia, BUT could lead to progression of neurological deterioration (if B12 def undetected as a result)

Question 34

B12

• name
• sources
• forms: synthetic and active

Answer 34

cobalamin

• sources: foods of animal origin (produced by bacteria, ex. in cattle rumen), also fortified cereals, soy milk
• forms
  
  • ​synthetic: cyanocobalamin
  • active: methylcobalamin, deoxyadenosylcobalamin

Question 35

B12 digestion and absorption

Answer 35

UNIQUE

• salivary glands: release R protein
  
  • R protein and protein-bound B12 move to stomach
• stomach:
  
  • B12 is released from its binding protein
  • B12 binds to R protein
  • parietal cells release IF (intrinsic factor)
  • R-bound B12 and IF move to duodenum
• duodenum: pancreatic enzymes clear R-protein-bound B12, allowing B12 to bind to IF
  
  • ​IF-bound B12 moves through intestines to ileum
• ileum: IF receptors allow internalization of B12 to ileal epithelial cells
  
  • in epithelial cells, B12 is released from IF
  • B12 binds to transcobalamin II, moves to liver via hepatic circulation
  • due to enterohepatic circ, can be good for several years

Question 36

B12 functions

Answer 36

**B12 and folate depend on each other for activation**

• regeneration of Met, synthesis of DNA, synthesis of RNA
• metabolism of odd-numbered FAs and many a.a.s
• helps maintain nerve cells

Question 37

B12 deficiency

Answer 37

• deficiency
  
  • ​malnutrition (ex. vegan diet w no supplementation)
  • issues with absorption
    
    • pernicious anemia: damage to parietal cells via autoimmune disease: decrease in IF
    • atrophic gastritis with aging, damages cells of stomach: low HCl and IF production
    • decreased gastric acid production (antacids/proton pump inhibitors)
    • terminal ileum removal (site of B12 abs)
• symptoms
  
  • megaloblastic anemia
  • nerve damage
  • painful, swollen tongue

Question 38

B7/biotin

• name
• functions
• deficiency
• toxicity

Answer 38

biotin [not known as B7]

• function
  
  • ​coenzyme in carboylation rxn
  • needed by ABC carboxylases (ATP, biotin, CO2)
  • req for metabolism of carbs, fats, proteins
• deficiency
  
  • ​rare
  • sometimes seen as biotinidase deficiency (enzyme needed to recycle active form of biotin) : skin rash, hair loss, convulsions, impaired growth
  • also seen with excessive consumption of raw eggs : excess avidin (binds biotin v tightly)
• toxicity
  
  • ​none known

Question 39

biotinidase deficiency

Answer 39

• inability to recycle biotin
• inherited: autosomal recessive; part of newborn screening in US
• symptoms
  
  • hypotonia (weak muscles), seizures, alopecia (hair loss), eczema, dept delays, lactic aciduria

Question 40

B5/pantothenic acid

• sources
• form
• functions
• deficiency/toxicity?

Answer 40

pantothenic acid [not known as B5]

• sources: meat milk, many veggies
• form: part of coenzyme A (acyl and acetyl group carrier)
• function
  
  • ​essential for activation of FAs and fat metabolism (synthesis of FAs, triacylglycerol, cholesterol, acetylcholine)
  • cell membrane symthesis
• deficiencies are rare, toxicity: none known

Question 41

interactions among B vitamins [3 examples]

Answer 41

• folate and B12 are dependent on each other for activation
• FMN (riboflavin, B2) is key for conversion of B6 (pyridoxine) to PLP
• FMF, PLP, and iron are required for conversion of Trp to niacin (B3)
• B vitamins are all involved directly or indirectly in energy metabolism
  
  • sources often have overlaps of B vitamins
• deficiencies can be linked, with common symptoms (cheilosis, glossitis) and it can be hard to tell what vitamin/deficiency is actually responsible for a symptom

Question 42

vitamin C

• name
• sources

Answer 42

ascorbic acid

• sources: fruits, vegetables

Question 43

C functions

Answer 43

• collagen formation
  
  • strengthening bones and blood vessels
  • anchoring teeth in gums
  • tissue repair
  • wound healing
• water soluble antioxidant
• synthesis of carnitine: key for FA degradation
• synthesis of neurotransmitters: norepi
• enhances intestinal abs of non-heme Fe (increases bioavailability of Fe from food)

Question 44

vitamin C: antioxidant ability

Answer 44

• vitamin C readily donates electrons to free radicals and ROS
• protects proteins, nucleic acids, cabs, lipids from oxidative damage
• vitamin C can be reduced back to its active form

Question 45

vitamin C: collagen synth

Answer 45

• used as a cosubstrate/cofactor by two enzymes involved in collagen synthesis
  
  • prolyl hydroxylase: catalyzes selective mod of Pro → hydryxproline
  • lysyl hydroxylase: catalyzes conversion of Lys → hydroxylysine

vitamin C def leads to nonfunctional collagen in blood vessels and bones

Question 46

vitamin C: role in neurotransmitter synth

Answer 46

norepi synthesis requires vitamin C

• explains neurological dysfunction and lassitude seen in scruvy

Question 47

vitamin C deficiency risk factors

Answer 47

• urban/poor adults (food deserts/low access to fruits and veg)
• severe bones/fractures (higher demand for vit C for collagen synth)
• alcohol and/or smoking

Question 48

scurvy

Answer 48

• ​muscle weakness, jt pain
• loose teeth, bleeding swollen gums (scorbutic gums)
• bruised skin, pinpoint hemmorhages (spontaneous internal bleeding - bad blood vessels), impaired wound healing
• fatigue

Question 49

vitamin C toxicity

Answer 49

vit C can be metabolized to oxalic acid

• pt with history of oxalate kidney stones should avoid high doses

Question 50

vitamin C as medicine

Answer 50

• doesnt prevent, but can reduce severity of common cold
• more research needed:
  
  • might reduce oxidation of LDLs
  • might help reduce risk of cancer/aid in cancer treatment

Question 51

look at and memorize last slide

Answer 51

look at and memorize last slide