Midterm 2 (Lec 7)

Question 1

Vitamin A

Answer 1

Generic term for a large number of related compounds with vitamin A activity (RETINOIDS)

along time treatment for night blindness

3 key forms of retinoids:
- retinal: VISION
- retinol: (TRANSPORT) (need a binding protein since vit A is fat soluble) gets converted to other forms
- retinoic acid (HORMONE)

Question 2

Vitamin A interconversions

Answer 2

Retinyl ester (foods in fat, storage in liver)

<->

Retinol (transport form attached to RBP) (alcohol)

<->

Retinal (vision) (aldehyde)

<->

Retinoic acid (gene expression)

Question 3

Carotenoids

Answer 3

Over 600

Some carotenoids have provitamin A activity (can be converted to vitamin A):
- beta carotene (most potent)

Others cannot be converted to vitamin A

Question 4

Vitamin A and carotenoids food sources

Answer 4

Vitamin A (retinoids)
- animal foods
- ex: oat milk fortified to be similar to whole milk, margarine fortified to be similar to butter

Carotenoids
- plant foods

Question 5

Vitamin A bioavailability

Answer 5

Rate and extent at which vitamin is absorbed and utilized

Depends on amount in food, amount absorbed, amount utilized
- retinoids (animal sources) much better absorbed

RAE = retinol activity equivalents

1 RAE equals (best to worst bioavailability):
- 1 ug of vitamin A (retinol)
- 2 ug of supplemental beta carotene
- 12 ug of dietary beta carotene
- 24 ug of other active carotenoids

(Just know order)

Question 6

Vitamin A metabolic functions

Answer 6

VISION
- retinAL (retinas in eyes)
- participates in the visual cycle
- initiated by light, end result is action potential

REGULATION OF GENE EXPRESSION
- retinOIC ACID
- reproduction, growth, integrity of immune system and epithelial cells

Question 7

Vitamin A regulation of gene expression

Answer 7

Retinoic acid can act as a steroid hormone (as well as vitamin D)

Retinoic acid actually binds to the DNA
- may increase or decrease transcription of specific proteins and affect gene expression
- influence numerous physiological processes

Most of the physiological effects of vitamin A result from its role in regulating gene expression, except for its role in VISION

Question 8

Vitamin A regulation of gene expression steps

Answer 8

1. Retinol travels to target cell membrane
2. Reitnol-> retinal -> retinoic acid
3. Retinoic acid travels intracellularly to the nucleus by CRABP (cellular retinoic acid binding protein)
4. Retinoic acid attaches to DNA receptors and alters transcription

Question 9

Vitamin A regulation of gene expression effects

Answer 9

Key physiological effects that involve vitamin A modulation of transcription :
- REPRODUCTION
- GROWTH
- IMMUNITY: maintains integrity of skin
- OTHER EPITHELIAL CELLS: role in differentiation of cells

Question 10

Vitamin A nutrient interactions: ZINC

Answer 10

Vitamin A needs zinc because zinc is involved in many aspects of vitamin A metabolism

Zn is needed for synthesis of RBP
Zn is needed for release of vitamin A from liver storage
Zn is needed for conversion of retinol to retinal

Therefore Zn deficiency interferes with Vitamin A status

Question 11

Vitamin A nutrient interactions : IRON

Answer 11

Vitamin A helps iron

Vitamin A helps mobilize iron from storage to help develop RNC for incorporation into hemoglobin
Relates to vitamin A’s role in differentiation of RBCs

Combination of vitamin A and iron helps address iron deficiency more effectively than iron alone

Question 12

Vitamin A deficiency main effects

Answer 12

Night blindness is a key early sign
- Bitots spots: white foamy lesions in the eye (great physical biomarker before it worsens)
-Due to lack of vitamin A in the back of the eye (retina)
-VERY common in developing countries , especially preschool aged children

Xerophthalmia
- progresses to lack of vitamin A in the front of the eye (cornea)
- corneal ulcerations, scarring, IRREVERSIBLE blindness
- leading cause of blindness in many developing countries

Question 13

Vitamin A deficiency other effects

Answer 13

Decreased growth

Failure to reproduce

Increased susceptibility to infection : considered a nutritionally acquired immunodeficiency disease

Keratinization of epithelial tissues : cells change shape and secrete keratin

Question 14

Vitamin A toxicity issues

Answer 14

Can be toxic due to liver storage

HYPERVITAMINOSIS A
- headache, vomiting, bone and joint pain, liver damage
- due to overconsumption of vitamin A, NOT carotenoids
- long term consumption in excess of 10x the RDA

TERATOGENIC RISK
- risk of birth defects, need to avoid during pregnancy
- due to vitamin A NOT carotenoids

Excessive carotenoids can cause carotenemia
- yellow orange ish skin
- distinct from jaundice (it’s not seen in eyes)

Question 15

Vitamin K Types

Answer 15

Vitamin K1
-phylloquinone
- synthesized by plants

Vitamin K2
- menaquinone
- synthesized by intestinal bacteria

Vitamin K3
- menadione
- synthetic form
- not sold as a dietary supplement

Question 16

Vitamin K metabolic role ?

Answer 16

Required as a coenzyme for the carboxylatuin of glutamic acid (GLU) to gamma carboxyglutamic acid (GLA)

Therefore a vitamin K dependent carboxylation

Glutamic acid residue of vitamin K proteins

Post translational modification

GLA sole purpose is to interact with calcium - important for:
- blood clotting
- bone proteins

Question 17

Vitamin K and blood clotting

Answer 17

Depends on vitamin K

Involves more than 12 proteins and calcium
- 7 if the, are vitamin K dependent proteins

Clotting is a CASCADE - aka clotting has to be activated (it’s not constantly happening)

Inactive factors are converted to active factors
- all require calcium to be activated

Activation needs to be done because we don’t want our blood clotting constantly

Question 18

Clotting factor cascade

Answer 18

Proteins dependent on vitamin K for synthesis
- the vitamin K carboxylates the GLU residue to GLA which allows calcium to bind

Proteins dependent on calcium for activation

• Prothrombin to thrombin
• fibrinogen to fibrin
• can cross linked fibrin = CLOT

Question 19

Vitamin K dependent blood coagulation proteins

Answer 19

Synthesized in the liver

have multiple GLA residues
- allows for binding if multiple calcium ions

Chelates calcium and forms bridge on membrane at injury site

Lead to fibrin formation - allow clot to form

Question 20

Prothrombin time

Answer 20

PTT - measurement of how long it takes for blood to clot

Measures presence of five clotting factors

High prothrombin time = insufficient amounts of vitamin K to carboxylate GLU (low vit K)

Question 21

Vitamin K cycle

Answer 21

Participation of vitamin K in the carboxylation of proteins is a cyclical process

Vitamin K is regenerated, following participation in carboxylation

STEPS
- vitamin KH2 (fully reduced form of vitamin K, ready to carboxylate) participates in carboxylation of GLU to GLA and is converted to vitamin K epoxide
- vitamin K epoxide is converted to vitamin K by vitamin K epoxide reductase
- vitamin K is reduced back to vitamin KH2 (fully reduced form is regenerated, ready to carboxylate again) by vitamin K (quionone) reductase

Question 22

Warfarin

Answer 22

Prescribed for people at risk of thrombotic events also as rat pesticide

Indirect vitamin K antagonist
- doesn’t inhibit the vitamin k carboxylase itself
- instead it blocks the regeneration of vitamin KH2 (fully reduced K) by inhibiting the vitamin K cycle enzymes:
— vitamin K (quinone) reductase
— vitamin K epoxide reductase

Stops the vitamin K cycle, decreases blood clotting

People on warfarin should decrease vitamin K intake

Question 23

Bone GLA protein BGP aka osteocalcin

Answer 23

Vitamin K dependent protein

Synthesized by osteoblasts (build up protein)

Contains 3 GLA residues

Very abundant in bone, especially growing bone

GLA residues facilitate calcium binding

Promotes bone mineralization

Question 24

Matrix GLA protein (MGP)

Answer 24

Vitamin K dependent protein

Contains 5 GLA residues

Found in bone but also blood vessels - role in vessels is more clear than bone

Reduces calcification (opposite of what’s expected of vitamin K protein) of blood vessels which has implications for CVD - active area of research

Question 25

Vitamin K food sources

Answer 25

Phylloquinone major form in foods
- green leafy vegetables

Menaquinone form present in fermented foods and some animal foods - also what’s synthesized from our intestinal bacteria

Question 26

Vitamin K deficiency

Answer 26

Uncommon in healthy adults

Several factors prevent deficiency
- widespread distribution of vitamin K in foods
- vitamin K cycle, conserved vitamin K
- microbiological flora of the gut (we can synthesize menaquinone form)

Symptoms
- prolonged blood clotting time
- easy brushing and bleeding
Susceptible groups:
- extended antibiotic use
- newborns exclusively breast fed (breast milk is a poor source of vitamin K- lactating moms recommended to supplement with vitamin K)

Question 27

Hemorrhagic disease of the newborn

Answer 27

Also called vitamin K deficiency bleeding (VKDB)

Bleeding does not stop and can include a fatal brain hemorrhage

Newborns may be susceptible to vitamin K deficiency because:
- poor placental transfer of vitamin K therefore born with low vitamin K status
- infant gut and breast milk are sterile
- neonatal liver is immature ; poor clotting factor synthesis
- vitamin K cycle may not be fully functional
- breast milk is low in vitamin K

Need prophylactic vitamin K (injection) at birth

Question 28

Vitamin K and Covid 19

Answer 28

Thromboembolism occurs in Covid 19 patients (blood clot in a blood vessel that comes loose and blocks another blood vessel)

Vitamin K preferentially used to help blood to clot and reduces amount for matrix GLA protein

Covid patients had more inactive matrix GLA protein than controls

Question 29

Vitamin K and cognition

Answer 29

Relates to menaquinone form of vitamin K and overall role of gut microbiota in cognition

Study shows a link between certain isoform of menaquinone and cognition