Fat-Soluble Vitamins Flashcards
What are the Fat Soluble Vitamins?
ADEK
General properties for fat soluble vitamins?
- require bile and fats for absorption
- excess stored in liver and adipose tissue
- not readily excreted (because of efficient enterohepatic circulation); results in increased risk of toxicity
How are vitamins unbound to proteins?
Vitamins are bound to proteins as we eat them, but once in the stomach, proteins are degraded into small peptides releasing vitamins.
Where does absorption occur for fat-soluble vitamins?
In the jejunum
Explain how absorption of fat-soluble vitamins occur
In the jejunum, fat-soluble vitamins forms micelle with bile salts allowing them to be passively transported into the intestinal enterocytes.
What occurs once the micelle enters the intestinal enterocyte?
In the enterocytes, micelles are packaged into chylomicrons and released into the lymphatic system. Once inside the lymphatic system, chylomicrons travel up the thoracic duct and enter the left subclavian vein.
Where do we obtain vitamin A from?
Either from animal foods in the form of retinyl esters or from plant foods as beta carotene
Discuss the conversion of the different forms of vitamin A in the body.
Retinol (which comes from retinyl esters) to retinal (which comes fro beta-carotene) is reversible. Retinal to retinoic acid is irreversible.
Sources of vitamin A
liver, sweet potatoes and carrots
Does the ingestion of equal amounts of beta carotene and retinyl esters yield similar amounts of vitamin A?
No. The absorption of beta carotene is not as efficient as that of retinyl ester
What is the form of vitamin A circulating in chylomicrons?
Retinyl ester
Where is retinyl ester converted to retinol?
In the hepatocyte
After conversion from retinyl ester to retinol, where is retinol stored?
Retinol is transported into stellatte cells for storage
What are stellate cells?
Account for 5%-8% of the cells in the liver. In a healthy liver, stellate cells are quiescent and contain numerous vitamin A lipid droplets, constituting the largest reservoir of vitamin A in the body
Function of retinol?
Supports reproduction and major transport and storage form
Function of retinal?
Active in vision
Function of retinoic acid?
Regulates cell differentiation, growth, and embryonic development
Function of beta-carotene?
Antioxidant
Why is retinoic acid unique?
Retinoic acid functions as a transcription factor, which means it participates in protein synthesis and cell differentiation through regulating gene expression (via RAR - its nuclear receptor)
Name specific cells affected by retinoic acid
Retinoic acid promotes differentation of both epithelial cels and goblet cells which protects mucous membranes
Pharamacological use of retinoids?
- Retinoic acid - treatment of acute promyelocytic anemia
- Tretionin - specifically Retin-A - treatment for acne, agining, dark pigments
- Isotretinoin - specifically accutane - oral treatment for cystic acne but is a teratogenic, therefore women who are using Accutane are required to use reliable forms of birth control
What is the pigment molecule found in rods (a cell of the retina)
Rhodopsin
What is rhodopsin?
Rhodopsin is composed of a protein caled opsin which is bonded to a molecule of retinal.
Explain how light affects the conformation of rhodopsin
As light interacts with rhodopsin, retinal changes from cis to trans configuration. Configuration change (cis to trans) releases retinal from opsin. Alone, opsin initiates a signal transduction cascade to nerve cells that communicate with the brain’s visual center. Trans retinal is enzymatically converted back to cis retinal which combines with opsin to regenerate rhodopsin.
What is a primary deficiency?
Inadequate intake
What is a secondary deficiency?
Poor absorption of fats
What is a deficiency in vitamin A called?
Hypovitaminosis A
What diseases can cause a secondary deficiency in vitamin A?
Cystic fibrosis, Crohn’s disease, liver disease, excessive alcohol intake
Symptoms of vitamin A deficiency?
Night blindness . If left untreated, it can progress to complete blindness known as xerophthalmia
Explain how a deficiency in vitamin A can lead to dry eyes.
Reduction in goblet cells and production of mucin leads to dry eyes.
Other changes developing with vitamin A deficiency
Bitot spots, corneal ulcer and keratomalacia
What causes corneal ulcers (keratitis)?
Due to inflammation of cornea
What causes keratomalacia?
Due to softening of the cornea
How is immunity affected in patient with a vitamin A deficiency?
Immunity is impaired
What is keratinization?
Kertinization, also known as hyperkeratosis, results from a vitamin A deficiency. The skin becomes dry, rough and scaly.
Results of toxiticy of vitamin A
birth defects
What are the birth defects in a child whose mother took accutane?
Cranofacial malformations and malformations of the CNS, thymus, and heart
Symptoms of Beta-carotene excess
Not harmful. Excess beta-carotene is stored in the fat under skin
How is vitamin D different from other nutrients?
Vitamin D can be synthesized in the body with the help of UV light using cholesterol as a precursor
Describe what occurs in the skin that leads to vitamin D3 formation.
In response to sunlight exposure, pro-vitamin D3 (7-dehydrocholesterol) is converted to pre-vitamin D3. Pre-vitamin D3 undergoes isomerization to become Vitamin D3 (cholecalciferol).
What form of vitamin D is food?
Vitamin D3 (cholecalciferol)
Describe what occurs in the liver, with regard to vitamin D.
Vitamin D3 binds to a vitamin D-binding protein in the bloodstream and is transported to the liver. D3 is hydroxylated by the liver. Enzyme responsible is 25-hydroxylase. The result is 25(OH)D3
Describe what occurs in the kidney, with regard to vitamin D.
25(OH)D3 is further hydroxylated in the kidney by (1-OHase). This yields the active 1,25 (OH)2D3 which is calcitriol
Sources of vitamin D?
Several types of fish, mushrooms, and fortified milk
Functions of vitamin D?
calcium and phosphorus homeostasis (main), bone health (main), immune function, reduction of inflammation and apoptosis, blood pressure regulation, regulation of gene expression as a pro-hormone
How does vitamin D modulate gene transcription?
The active form of vitain D, calcitriol, can modulate gene transcription following binding to its cognate nuclear receptor, the vitamin D receptor (VDR)
Factors that contribute to a vitamin D deficiency
Dark skin, breastfeeding without supplementation, lack of sunlight, use of non-fortified milk, lose ability to active vitamin D (elderly), little or no milk in diet, vegan diet
Diseases resulting from a vitamin D deficiency
Rickets, osteomalacia, osteoporosis
Symptoms of Rickets?
(1) Growth retardation, skeletal abnormalities such as bowing of the legs. (2) Poorly formed attachments of bones to cartilage. (3) Delayed closure of fontanel resulting in rapid enlargement of head
Who in the US is more suspectible to rickets?
young, breast-fed black children. Breast milk does not have much vitamin D and pigments in dark skin reduce vitamin D synthesis
What is osteomalacia?
poor mineralization of bones due to vitamin D deficiency leads to soft, brittle and deformed bone
How can osteomalacia develop?
Result of taking anticonvulsants such as phenobarbital and phenytoin for a long period of time. Also, in patients with chronic kidney disease where the production of the active form of vitamin D is greatly reduced
What causes toxiticis in vitamin D?
occurs with supplementation; cannot occur via sunlight or dietary sources
Harm from increased vitamin D?
Excess vitamin D increases the concentration of blood calcium which tends to precipitate in the soft tissues suh as blood vessels, kidney, heart, lungs where it can cause death
Another name for vitamin E?
Tocopherol
What is tocopherol?
Tocopherol is a general term describing 8 related compounds (4 tocopherols: alpha, beta, gamma & delta and 4 tocotrienols), one of which has vitamin E activity.
Which compond has vitamin E activity?
D-isomer of alpha tocopherol
Sources of vitamin E?
Nuts and oils
Functions of vitamin E?
effective lipid soluble antioxidant (main), inhibition of platelet aggregation and monocyte adhesion, assisting in maintenance of fertility
How is vitamin E an effective lipid soluble antioxidant?
Protects polyunsaturated fatty acids within cell membranes from peroxidation
What is lipid peroxidation?
Lipid peroxidation is the oxidative degradation of lipids. It is the process in which free radicals “steal” electrons from the lipids in cell membranes, resulting in cell damage.
Common target for peroxidation?
Unsaturated fatty acids present in membrane phospholipids
How does vitamin E stop peroxidation?
Vitamin E stops peroxidation by donating a hydrogen to lipid radicals
What is vitamin C’s role in aiding vitamin E?
After donating its hydrogen, active vitamin E is regenerated by vitamin C
Who generates the most reactive oxygen species?
The mitochondrial electron transport chain generates most of the reactive oxygen species such as superoxide or hydrogen peroxide
Results from a deficiency in vitamin E?
characterized by the premature destruction of red blood cells leading to hemolytic anemia
How could a vitamin E deficiency occur?
inadequate intake (rare) or fat malabsrption because of cystic fibrosis or pancreatic insufficiency (secondary deficiency) or in preterm infants
How can vitamin E toxicity occur?
rare; but may develop when exogenously supplemented
Results of excess vitamin E?
(1) interference with vitamin K which can lead to issues with clotting and increase likelihood of a hemorrhage
(2) nerve daage
How is vitamin K unique?
Synthesized by the bacteria in our gut
Animal source of vitamin K?
menaquinones (also the form synthesized by gut bacteria)
Plant source of vitamin K?
phylloquinones
Sources of vitamin K?
Green, leafy vegetables and oils
Function of vitamin K?
involved in blood clotting and bone mineralization
What is vitamin K’s main role as a cofactor?
Vitamin K is a required cofact for the posttranslational modification of glutamate to the unusual amino acid, gamma-carboxyglutamate (Gla)
Which enzyme catalyzes the conversion of glutamate to gamma-carboxyglutamate (Gla)?
Gamma-glutamyl carboxylase
What is the importance of gamma-carboxyglutamate (Gla) ?
Several blood proteins require the presence of nine to thirteen Gla residues for normal function; these are the so called vitamin K-dependent (VKD) proteins
Role of vitamin K in blood coagulation?
Vitamin K participates in both the intrinsic and extrinsic blood-clotting pathways
Causes of a possible deficiency in vitamin K?
Deficiency of vitamin K may develop with the use of antibiotics and malabsorption. Newborns have low stores of vitamin K at birth due to the laack of gut bacteria.
Symptoms of vitamin K deficiency?
hemorrhaging, bruisability, mucosal bleeding
How could a patient have a toxicity in vitamin K?
Toxicity may develop in patients taking warfarin. Warfarin works by decreasing the activity of vitamin K
What do vitamins A, D, and K have in common?
Play important role in bone growth and remodeling
What is the relationship between vitamin E and A?
Vitamin E protects vitamin A from oxidation
