Midterm 2 (Lec 7) Flashcards
Vitamin A
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)
Vitamin A interconversions
Retinyl ester (foods in fat, storage in liver)
<->
Retinol (transport form attached to RBP) (alcohol)
<->
Retinal (vision) (aldehyde)
<->
Retinoic acid (gene expression)
Carotenoids
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
Vitamin A and carotenoids food sources
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
Vitamin A bioavailability
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)
Vitamin A metabolic functions
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
Vitamin A regulation of gene expression
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
Vitamin A regulation of gene expression steps
- Retinol travels to target cell membrane
- Reitnol-> retinal -> retinoic acid
- Retinoic acid travels intracellularly to the nucleus by CRABP (cellular retinoic acid binding protein)
- Retinoic acid attaches to DNA receptors and alters transcription
Vitamin A regulation of gene expression effects
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
Vitamin A nutrient interactions: ZINC
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
Vitamin A nutrient interactions : IRON
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
Vitamin A deficiency main effects
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
Vitamin A deficiency other effects
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
Vitamin A toxicity issues
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)
Vitamin K Types
Vitamin K1
-phylloquinone
- synthesized by plants
Vitamin K2
- menaquinone
- synthesized by intestinal bacteria
Vitamin K3
- menadione
- synthetic form
- not sold as a dietary supplement
Vitamin K metabolic role ?
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
Vitamin K and blood clotting
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
Clotting factor cascade
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
Vitamin K dependent blood coagulation proteins
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
Prothrombin time
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)
Vitamin K cycle
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
Warfarin
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
Bone GLA protein BGP aka osteocalcin
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
Matrix GLA protein (MGP)
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
Vitamin K food sources
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
Vitamin K deficiency
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)
Hemorrhagic disease of the newborn
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
Vitamin K and Covid 19
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
Vitamin K and cognition
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
