Beleh Fat Soluble Vitamins

What are some therapeutic uses of Vitamin D? (Table)

-Indicated for osteoporosis prevention/treatment, hypoparathyroidism, hypocalcemia, hypophosphatemia

What is the key biological function of Vitamin D? What other roles does it help with?

-Key role of vitamin D is bone formation -Regulates expression of genes that maintain calcium homeostasis -Creates heterodimer by binding a nuclear hormone receptor (VDR) that then binds to an RXR; this modulates the expression of genes -The gene products enhance absorption of Ca and phosphate from the small intestines, promotes their mobilization from bone, and decreases their excretion by the kidney

Where does the light enter in a human rod cell? in which part of the cell is the opsin found?

-Light enters through the synaptic body -Opsin can be found in the outer segment in the disks

What is the main function of vitamin E? What other ways is it used?

-Main function believed to be antioxidant -Intercept lipid radicals -Can inhibit protein kinase C -Can alter expression/activities of enzymes in immune and inflammatory cells

Explain the general SAR of vitamin A and the analogs. How are these products mainly used?

-Mainly used in acne products

At what doses can vitamin A toxicity occur? What are the signs/symptoms?

-May occur at 200mg in adults, and half that in children (100mg) -May include headache, nausea/vomiting, increased CSF pressure, blurred vision, bulging of the fontanelle in infants

Briefly explain the structures of vitamin K. (Diagram)

-Notice the quinone structure

Interaction with what other receptors are causes other vitamin A functions? What can happen if there are vitamin A deficiencies?

-Other functions arise from interaction of retinoid acid with nuclear retinoid receptors (RARs) and retinoid receptors (RXRs) -Bind to DNA and modulate transcription -Deficiencies can cause night blindness, dry/scaly skin, and overgrowth of teeth and bones in infants

Where is vitamin D2 produced? Explain its metabolism.

-Produced in plants from ergosterol; has similar properties to D3

Explain the basic components of the antioxidant mechanism. What role does the quinone play in this mechanism?

-Quinone gets rid of the toxic metabolites and oxygens -In this case the quinones are helpful for two reasons: 1) quinone is converted back to vitamin E very quickly, which is safe. 2) the quinones do not all gather in one place (such as the liver), but rather all over the body. This makes them much safer because there isn't mass accumulation in one area.

What are the three major vitamin A forms? What physiological functions to they have a role in?

-Retinol (top) -Retinal (left) -Retinoic acid (right) -Role in bone growth, reproduction, embryonic development, protein synthesis, tissue differentiation, glycoprotein synthesis

Explain how retinol plays a role in vision.

-Retinol is actively transported into cells and oxidized by retinol dehyrogenase -Retinal is converted to 11-cis retinal by retinal isomerase -Changes the structures conformation at the 11th carbon

Explain the "front end" of phototransduction. (Diagram) What are some interesting features of the molecule involved at the area of light reaction?

-Rhodipsin hit by a photon -Although the cis formation is quite stable, the light reaction causes isomerazation and converts back into the old trans form

When do you see vitamin E deficiency? What about toxicity?

-Severe cases of malnutrition or genetic defects will cause deficiency; can result in neurological symptoms, damage to the retina, and muscle weakness -Toxicity is difficult to achieve (>3000 mg/day did not show significant toxicity); >1000 mg/day in infants can lead to hepatotoxicity

What are the mainly used vitamin E derivates and where are they isolated from? How do their structures vary?

-The OH group off the phenyl ring must stay attached, other wise the molecule is no longer Vitamin E

Explain the pathway of vitamin K and how it's used in clotting.

-The vitamin K epoxide is converted in a hydroquinone through vitamin K reductase -The hydroquinone is important for binding CO2 to glutamate through the Vit K dependent carboxylase; this reaction forms the gamma-carboxyglutamate -Carboxyglutamate increases Ca binding, which helps the clotting factors -The alkoxide in the center has a negatively charged Oxygen that goes in and extracts the Blue hydrogen, giving the glutamate the negative charge that can react with the CO2

What are the therapeutic uses of vitamin K? What DDIs should be noted?

-Therapeutic uses include: deficiencies, antidote for warfarin OD, topical creams for post-operative bruising, Vit K injections for newborns -DDIs: cephalosporin antibiotics, warfarin, orlistat, bile acid sequestrates

How many double bonds are found on a vitamin A molecule. What position are they in? Is vitamin A easy to synthesize? Why or why not?

-There are 5 conjugated double bonds -All are in the trans position -The conjugated bonds are easily isomerized by light, which makes synthesis very difficult

Explain the biochemical reactions that are responsible for vision (Diagram)

-Think of the process as a signal transduction pathway -The 5'-GMP form will close the channels, leading to glutamate production and to the events that cause vision

Name some therapeutic uses of vitamin A and the analogs.

-Vitamin A deficiency -Increased immunity in infants -Skin disorders (acne, psoriasis, Kaposi's sarcoma) -Acute promyelocytic leukemia (APL) -Perhaps cancer prevention?

Why is vitamin D3 not considered a true vitamin? Which "form" is it? Explain its metabolism (Diagram).

-Vitamin D3 is produced from 7-dehydrocholesterol by UV irradiation. This is interesting since because D3 is the "animal form," and most other vitamins need to come from other organic sources

Having a deficiency in which minerals will cause problems with vitamin A?

-Zinc deficiency alters vitamin A metabolism; it is needed for synthesis of retinol binding protein (RBP), hydrolysis of retinal palmitate, conversion of retinol to retinal -Deficiencies of vitamin A can also exacerbate iron-deficiency anemia

True or False: Both ß-carotene and vitamin A have OD toxicities.

False: only Vitamin A has OD toxicity

What are the conformations seen in the pre/post-light forms of rhodopsin?

Pre-light = 11-cis bound Post-light = all trans bound

Name some of the drugs that cause DDIs when used with vitamin A.

-Any vitamin A based drug -Tetracycline antibiotics -Anticoagulants (warfarin) -Oral contraceptives -Bile acid sequestrants -Omeprazole (other PPIs)

What are some common characteristics of the fat soluble vitamins?

-Associated with lipids in food -Absorbed from the intestine with dietary lipids -Stored in the liver and converted (to their active form) by organism

In what form is retinol transported to the liver for storage. What important protein is responsible for this?

-Converted to its esterified form for liver storage. -Vitamin A is transported and complexed to retinol binding protein (RBP)

In the vision process, how doe 11-cis-retinal interact? What is the name of the complex?

-Coupled to lysine on the opsin; coupled as a Schiff base -Forms a whole complex called Rhodopsin

How common is vitamin K deficiency? What are the signs/symptoms? How common is toxicity?

-Deficiency is uncommon: generally results from intestinal obstruction, celiac or Crohn's disease -Symptoms: excessive bleeding, stomach pains, bone effects -No real toxicity associated with Vit K

Which factors in the coagulation cascade does vitamin K dependent carboxylase activate?

-Factors II, VII, IX, and X

What are some therapeutic uses of Vitamin E?

-Hemolytic anemia in premature infants -Macrocytic megaloblastic anemia in children -Suggested to be useful in CV disease, cataracts, immune function, cancer

Which sources contain provitamin ß-carotene? Where in the body is this provitamin cleaved? How?

ß-carotene dioxygenase - uses two oxygens to oxidize each side of the molecule -Enzyme controlled by feedback NADH dependent reductase then cleaves retinal to retinol -Enzyme not controlled by feedback