Vitamins and lipids (1.15) Flashcards
What are the 4 fat soluble vitamins?
A
D
E
K
What is the active form of vitamin A?
all-trans-retinol
What are the dietary forms of vitamin A? What foods?
Carotenoids
Retinyl-acyl esters
Red, yellow, and orange fruits and vegetables
How is dietary vitamin A converted into free carotenoid and free retinol in the intestine?
Dietary protein-bound carotenoids and retinyl esters enter stomach –proteases–> carotenoid and retinyl esters enter duodenum –hydrolases, esterases, and lipases–> free carotenoids and free retinol
What happens in the intestine after free carotenoids and free retinols are formed? Why?
Fatty acids, phospholipids, monoacylglycerol, and/or cholesterol are added
Gets incorporated into micelle
In what two forms does vitamin A leave the intestinal cell?
Retinoic acid…to liver via blood albumin
CRBPII-retinyl-palmitate…lymphatics in chylomicron –> to liver as chylomicron-remnant
Why does retinoic acid go to the liver?
The liver stores vitamin A in stellate cells…controls vitamin A homeostasis (30-86ug/dL)
After retinyl esters enter a hepatic parenchymal cell, how can the leave?
Stellate cells (to/back to storage) VLDL (to tissues)
After retinyl esters enter a hepatic parenchymal cell, they can be converted to retinol. How does retinol leave?
Retinol complexes with transthyretin and retinol binding protein (RBP) to go out to the serum
After retinyl esters enter a hepatic parenchymal cell, they can be converted to retinoic acid. How does retinoic acid leav?
Goes out to serum complexed with albumin…like it did from the intestinal cell
What kind of receptors are Retinoic Acid Receptors (RAR), Retinoic X Receptors (RXR), and some Peroxisome proliferator activated receptor (PPAR)?
Ligand activated transcription factors
What are the effects of RAR, RXR, and PPAR?
Increased differentiation of goblet cells
Decreased keratinization
Apoptosis of cancer cells
Maturation of dendritic cells
Recruitment of antibody secreting B cells to small intestine
How can carotenes be helpful if they are not cut?
Act as antioxidants…their double bonds can neutralize singlet oxygen and free radicals
What are the symptoms of vitamin A deficiency?
Anorexia Retarded growth Increased susceptibility to infections Alopecia Keratinization of epithelial cells Night blindness* Xeropthalmia (dry eyes d/t keratinization)* Bitot's spots (something with eyes)*
How is vitamin A deficiency diagnosed?
The Relative Dose Response (RDR)
How is the RDR calculated?
At what point is an RDR indicative of a deficiency?
RDRs > 20%
What is the Tolerable Upper Limit (TUL) of vitamin A?
3000ug/day
What can happen if vitamin A TUL is exceeded for a period of time?
Nausea/Vomiting Blurred vision* Headache Desquamation of skin Alopecia Ataxia Liver damage (from excess stellate cell growth and proliferation) Conjunctivitis/eye pain Teratogen at very high doses (Accutane--an acne medication)
What are the two forms of vitamin E? What food?
Tocopherols (saturated 16C acyl chains)
Tocotrienols (polyunsaturated 16C acyl chains)
Plant oils and wheat germ
How does vitamin E get into the liver?
Similar to vitamin A
Pancreatic lipase does its thing so vitamin E can enter intestinal epi cells…leaves as chylomicron for tissues…then to the liver in a chylomicron remnant
How is vitamin E sent to the tissues after being in the liver?
RRR steroisomers can be incorporated into and exported in VLDL
What is vitamin E’s function?
Antioxidant activity (d/t phenolic hydroxyl) in lipid bilayers
What other two vitamins does vitamin E interact with?
Vitamin C reduces oxidized vitamin E to active form
Vitamin K absorption and metabolism are INHIBITED by vitamin E
What are the symptoms of vitamin E deficiency?
Myopathy
Hemolytic anemia
Peripheral neuropathy
Ataxia…loss of vibratory sense
What can cause vitamin E deficiency?
Absorptive problems–premies, Crohn’s, short bowel syndrome
Inherited lipoprotein disorders
What are the two main forms of dietary vitamin K?
Phylloquinone (main form…in leafy greens)
Menaquinones (produced by fermentation…cheese)
What is a synthetic form of vitamin K used in animal feed that can be toxic to humans?
Menadione (liver toxicity)
What is the digestion/absorption process for vitamin K?
Same as E…which is the same as A…which is the same as fat
Where is vitamin K stored?
Cellular membranes–lung, kidney, bone marrow, and adrenal glands
What is vitamin K’s function?
Co-factor for gamma-glutamyl carboxylase –> activates clotting proteins (Factors IX, VIIa, and X)
What are the symptoms of vitamin K deficiency?
Coagulation disorder (increased PTT and bleeding)
What foods contain vitamin D?
Foods of animal origin
Besides the diet, how else can vitamin D be obtained?
Synthesized de novo from cholesterol
What is needed to make active vitamin D3?
Metabolism of skin, liver, and kidney
What is the main function of vitamin D?
Calcium homeostasis
Vitamin D is taken to the liver via the expected route, but how is it activated (start with de novo steps)?
Cholesterol + sunlight (skin) –> dietary form of vitamin D –liver–> 25-Hydroxycholecalciferol (main form circulating in blood) –kidney (PTH 1-alpha hydroxylase–> 1,25-OH D3 (active form)
When does the parathyroid secrete the PTH necessary to activate vitamin D?
When serum calcium is low (<8.5mg/dL)
How does vitamin D increase serum calcium levels?
Reabsorption from bones
Increased absorption in the gut
How does vitamin D increase intestinal calcium absorption?
Vitamin D Receptor acts as a ligand activated transcription factor –> tsl of calcium transport proteins (TRPV6 at brush border, calbindin in cytoplasm, and Ca ATPases at basolateral membrane…and alters claudin–tight junctions–to be more permeable to calcium)
If vitamin D causes increased translation of proteins, how can there be a response within seconds to minutes?
There is a transcription-independent rapid response… binds to other plasma membrane receptors
What are the symptoms of vitamin D deficiency?
Rickets (seizures, growth retardation, osteomalacia)
What can cause vitamin D deficiency?
Diet
Genetics
Absorption problem (Crohn’s)
What are the symptoms of vitamin D toxicity (most likely vitamin toxicity)?
Calcification of soft tissues
Hyperphosphatemia
Hypertension
What is the TUL of vitamin D in people >9?
4000IU