Fat Soluble Vitamins

What are the fat-soluble vitamins?

A, D, E, K

Where are fat-soluble vitamins stored?

Liver and adipose tissue

What is the function of vitamin A?

Vision, healthy skin, and cell differentiation

What is the function of vitamin D?

Calcium and phosphate metabolism, cell differentiation

What is the function of vitamin E?

Antioxidant (especially for lipids)

What is the function of vitamin K?

Synthesis of blood clotting proteins

What are the clinical features of a vitamin A deficiency?

Night blindness, growth retardation, and xerophthalmia

What are the clinical features of a vitamin D deficiency?

Rickets in children and osteomalacia in adults

What are the clinical features of a vitamin E deficiency?

Hemolytic anemia in newborns and neurological disorders

What are the clinical features of a vitamin K deficiency?

Bleeding

Excessive intake of what fat-soluble vitamins can cause toxicity?

A and D

What are the A vitamins?

Retinol, retinal, and retinoic acid

What vitamin A is found from plant sources?

Carotenoids, such as beta-carotene

Vitamin A is a cofactor required for the protein?

Opsin in the retina

Vitamin A acts as a transcription factor in…/

Retinoic acid receptors

What is the precursor to vitamin A?

Beta-carotene

Beta-carotene is cleaved in the intestine to produce…?

Two molecules of retinal

When retinal is reduced it creates?

Retinol

When retinal is oxidized it creates?

Retinoic acid

Conversion of beta-carotene into retinol is…?

Inefficient

How is vitamin A transported?

Transported to liver in chylomicrons

How is vitamin A stored?

Retinyl esters in liver and adipose

When vitamin A is secreted from the liver, it is associated with?

Plasma retinol-binding proteins complexed with transthyretin

11-cis retinal covalently links to opsin to form?

Rhodopsin

When light hits the retina, what happens to rhodopsin?

Activates a GTP-binding protein, transducin. This activates a cyclic GMP phosphodiesterase, which causes a visual signal

How does vitamin A work as a transcription factor?

Retinoic acid binds to RAR and RXR receptors, leading to the synthesis of specific proteins

How is vitamin A used to treat acne?

Reduce inflammation, normalize follicle cell life cycle, reduce sebum production, reduce amount of skin cells within hair follicle that can cause blockage

How is vitamin A used to treat psorasis?

Reduces inflammation and promotes differentiation of epidermal keratinocytes

What is the basis behind acute promyelocytic leukemia (APL)?

A chromosomal translocation occurs that creates a PML-RARalpha gain-of-function protein that represses gene expression resulting in proliferation and inhibition of terminal differentiation

How does all-trans retinoic acid therapy treat APL?

Promotes reactivation of differentiation

ATRA therapy is usually combined with?

Arsenic trioxide

What is xerophthalmia?

Pathologic dryness of cornea, loss of mucus-secreting goblet cells

What are bitot spots?

Gray plaques on the conjunctiva

What is follicular hyperkeratosis or keratosis pilaris?

Overexpression of keratin in hair follicles

What are the sources of vitamin D?

Sunlight, fatty fish, liver, cheese, egg yolk, shiitake mushroom, fortified foods

What is the active form of vitamin D?

Calcitriol

How does skin make vitamin d3?

UV-B sunlight hits 7-dehydrocholesterol and it is converted into cholecalciferol

How does the liver make vitamin D?

25-hydroxylase adds an -OH group to carbon 25 of vitamin D3 to produce calcifediol

How does the kidney activate vitamin d?

1α-hydroxylase adds an -OH group to carbon 1, producing calcitriol

How does PTH affect vitamin d synthesis?

Induces 1α-hydroxylase expression (CYP27B1) in kidney proximal tubule in response to low plasma calcium

What is the function of 1,25-dihydroxy D3 (calcitriol)?

Maintain adequate levels of plasma calcium; stimulates renal reabsorption of calcium when the calcium level is low, stimulates calcium uptake by the intestine

Where are vitamin d receptors (VDR) expressed?

Intestine, bone, and kidney

What is the function of VDRs?

In calcitriol-bound state, VDR:RXR functions as a transcription factor and targeting calcium binding and transport proteins

What is rickets?

Soft and weak bones due to deficient mineralization of growth plates resulting in bowlegs

What is osteomalacia?

Demineralization of bone and poor mineralization of new bone (matrix intact)

What are the sources of vitamin K?

Leafy greens, gut flora, liver, egg yolk, plant oils, blueberries, pumpkin

Vitamin K is a cofactor for…?

gamma glutamyl carboxylase

What is the function of gamma-glutamyl carboxylase?

Promotes conversion of Glu to Gla in key blood clotting factors; enables their ability to bind calcium

What is the function of Gla residues?

Critical for a subset of proteins to bind calcium, including clotting factors. Important one is prothrombin!

When vitamin K participates in γ-carboxylation, it changes from its active, reduced form into an oxidized form called…?

Vitamin k epoxide

What is the active, reduced form of vitamin k?

Vitamin K hydroquinone

What enzymes convert vitamin k back into its active form?

Vitamin K epoxide reductase (VKOR)

Vitamin K reductase (VKR)

What is the mechanism of warfarin?

Acts as an anti-coagulant by preventing the conversion of vitamin k back to its active hydroquinone form

What can overcome the anticoagulant effect of warfarin?

Large quantities of supplemental vitamin k

What is prothrombin time?

Measures the time taken for blood to clot and can be used for the diagnosis of bleeding problems

An increase in prothrombin time can be due to…?

Vitamin k deficiency

Why is a dose of vitamin k given to all newborns (phylloquinone)?

Newborns have sterile intestine, human milk is low in vitamin k, and a vitamin k deficiency in newborns may result in a life-threatening bleeding disorder

What is the difference between vitamin c/k deficiency in regards to PTT?

Vitamin K deficiency increases PTT, it is normal in vitamin C deficiency (bleeding time is increased)

What is vitamin E also known as?

Alpha-tocopherol

What are the major sources of alpha-tocopherol?

Vegetable oils, nuts, whole grains, and green leafy veggies, liver, milk and eggs

In human liver, alpha-tocopherol is bound to…?

Alpha-tocopherol transfer protein and incorporated into lipoproteins to transport it to extrahepatic tissues

Where is vitamin e stored?

Adipose tissue

What is the function of vitamin e?

Reduces oxidative damage to membrane (esp RBCs) and plasma lipids; non-enzymatically terminates the free radical lipid peroxidation