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159 Cards in this Set
- Front
- Back
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basic definition of a vitamin
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-organic compound required by the diet in small amounts
-not oxidized to provide energy -not for structured purposes, but as cofactors |
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Pyruvate dehydrogenase has five cofactors. what are they?
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1. thiamin
2. riboflavin 3. niacin 4. pantothenic acid 5. lipoic acid |
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what cofactors are needed for alpha ketoglutarate dehydrogenase?
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same as pyruvate dehydrogenase
1. thiamin 2. riboflavin 3. niacin 4. pantothenic acid 5. lipoic acid |
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what enzyme converts pyruvate to acetyl coA?
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pyruvate dehydrogenase
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what enzyme Alpha-KG to succinyl CoA?
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alpha KG dehydrogenase
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Some characteristics of fat-soluble vitamins?
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-found in oil and fats
-require bile for abs -lymphatic system and CM for transportation -protein carrier often required -stored liver and adipose (toxicity risks) -needed in periodic doses |
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water soluble vitamins
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-thiamin
-niacin -B12 -biotin -ascorbic acid -riboflavin -b6 -folate -pantothenic acid |
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cofactor
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-chemicals required for enzymes ex. coenzyme, metal ion, lipid
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coenzyme
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small organic molecules required by enzymes
-NOT METAL |
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holoenzyme
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an enzyme with its cofactors
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apoenzyme
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an enzyme without it's cofactors
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mole
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contains Avogados number of molecules, (6.02*10^23) and contains a mass in grams=molecular weight
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1 molar =?
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180 g/L
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Vitamin A: two forms
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retinoids and carotenoids
-carotenoids: broadest term and ~10% have the ability to be converted to Vit A and retinoids |
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what are the prohormone forms of vitamin A ?
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B-carotene (plant)
all-trans-retinol (animal) |
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what is the plant version of vitamin a?
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b carotene
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what is the animal version of vitamin a?
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all-trans-retinol
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what is the alcohol form of vitamin a?
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retinol or all-trans-retinol
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what is the aldehyde form of vitamin a & what is it's specialty?
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11-cis-retinal and it's a visual cofactor
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what is the acid form of vitamin A? What is its purpose in the body?
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1. all-trans-retinoic acid and it's derivatives
2. 9-cis-retinoic acid 3. 13-cis-retinoic acid purpose- active hormone |
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what is special about the acid form of vitamin a?
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the double bonds gives a lot of forms with differ biological activities and affinities for certain receptors
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Storage of Vitamin A
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1. only vitamin with specific body storage sites & elaborate storage/release mechanism- may reflect it's toxicity
liver: 70% Adipocyte: 15% Remainder: kidney, ovary, intestines, heart |
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is vitamin a recycled?
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vitamin a is not recycled in lipoproteins (not present abundantly in VLDL)
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what kind of cell is vitamin a stored in?
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stellate cells until released by an unknown signal and is coupled by other transporters
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Ligands
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1. flat/planar structures
2. aromatic ring/conjugated double bonds 3. share receptors 4. hydrophobic 5. no cell membrane receptor (into cell by itself) |
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what are examples of ligands that have no cell membrane receptors? and what are the two groups of them called (what are they divided by)?
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1. Cholesterol derivatives: vit D, estrogen, progesterone, testoterone, glucocorticoids, mineralcorticoids
2. NON-cholesterol derivatives: vit A, thyroid hormone, ecdysone |
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which one of the ligand has a nuclear receptors?
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vit D
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Zinc fingers are rich in what kind of protein?
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cysteine
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what dimerize the two ligands together on the retinoic acid receptor?
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leucine zipper- it puts two of the receptors together
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do plants synthesize vit A?
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yes
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Steroid receptor superfamily
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- transcription factors that bind to target gene's promoter region
-activity depends on ligand binding (vit d active form, thyroid hormone, retinoic acid) -cross talk -homo & heterodimers -'orphan receptors' |
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vitamin a affects almost every cell type- how?
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it affects the differentiation and proliferation of almost every cell type by controlling transcription of target genes
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how does vitamin A effect c-fos & c-jun?
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transcription factors in many cells, antagonized by RA-RAR
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how does vitamin A effect osteonectin?
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regulates chondrocyte (cartilage cell) differentiation and matrix formation
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how does vitamin A effect collagenase?
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degrades the collagen bone matrix, turned off by RA
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how does vitamin A effect homeotic selector genes?
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transcription factors that control identity of embryonic structures as they are formed
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how does vitamin A effect alcohol dehydrogenase?
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turned on by RA
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how does vitamin A effect apolipoprotein A1?
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turned on by RA
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What is the main function of vitamin A?
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protein synthesis and cell differentiation
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Promotes differentiation of what two types of cells?
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1. epithelial cells
2. goblet cells |
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how does vitamin A promote differentiation of epithelial cells?
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1. inside: mucous membranes, linings of the mouth, stomach, intestines, lungs, urinary bladder; vagina, eyelids, sinus pathways
2. outside: skin |
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RA analogs are used for what?
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are used for chemotherapy for CA of epithelial origin basal cell carncinoma, melanoma, cervial dysplasia
uncontrolled proliferating cells-> normal differentiation (to promote CA normal differentiation) |
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Retinoic acid containing accutane and isotretinoin are used for what?
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epithelial disorders
- severe cystic acne: redifferentiates the sebaceus glands -psoriasis (autoimmune disorders): RA effects skin, immune system, Vit D -antiwrinkle cream |
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do goblet cells stop differentiating without Vit A?
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yes
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The relationship with vitamin A and immune fxn?
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-enhances t cell-mediated immunity
- one to five year old children have a 50% reduction in mortality with a 200,000 IU supplement - animal studies have shown impaired immune responses in Vit A deficiency in t cell mediated immunity, antibodiy synthesis, and lymphocyte proliferation |
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Reproduction and growth and it's relationship with Vit A
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1. Men- sperm development
2. Women- fetus development/embryogenesis a. defines spatial position while structure/organ is formed b. defines posterior (little finger vs thumb) c. dictates shapes of the heart, face, kidney, ear, eye d. bone remodeling |
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Isotretinoin syndrome
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increased Vit A content in skin products makes
1.misplace/missing ears 2.small/missing eyes 3.concave,mongoloid face 4.deranged neurons 5.mental retardation 6.open septum of the heart |
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teratogenic doses of Retinoic acid
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0.5-1.5 mg/kg/bw
toxic to embryos |
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what is the link of vitamin A and Fetal ETOH syndrome?
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it might be caused by an abnormal vit A metabolism
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b carotene is defined as not a pro but a..
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antioxidant
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what is the link b/n carotenoids and cancer?
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increased intakes of carotenoids and F&V have been correlated toa reduced risk to CA of the cervix, endometrium, breast, skin, and lung in some studies
increased intakes of carotenoids may be harmful to those with lung CA |
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Eye function and Vit A
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maintenance of the cornea of the eye
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bitot's spot?
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RA deficiency leads to a cornea abnormality that forms white foam patches, the cornea cells die and the cornea prolapses which then leads to blindness
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Vit A deficiency is the leading cause of what in the world?
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blindness
and night blindness |
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what part of the eye uses Vit A and what kind?
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in the retina there are rods (b&w) and cones (color). The rods use rhodopsin which is composed of opsin and retinal (11-cis-retinal) the aldehyde form of Vit A
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the visual cycle is independent of?
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the hormonal action of RA and the epithelial corneal differentiation by RA
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Toxicity of Vit A
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-teratogenicity (toxic to fetus)
-acute peeling, cracking, drying and redness of skin -clinical hypothyroidism -death |
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are carotenoids toxic?
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generally no
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why does toxicity of vit A cause clinical hypothyroidism?
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competition b/n Vit A and thyroid hormone at the receptors, which overwhelm the thyroid gland and get a deficiency of thyroid hormone
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is body growth affected by vit A deficiency?
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yes, there is a lack
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what are some confounding problems that would aggravate Vit A deficiency?
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1. measles
2. PEM- Kwashiorkor 3. Zn deficiency 4. Diarrhea and/or parasitic infection 5. Vit D toxicity |
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Measles and vit A
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-depletes the liver stores of vit A which worses vit A deficiency by an unknown mechanism
-major health problem in non-industrialized nations |
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PEM (Kwashiorkor) and Vit A
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insufficient RBP synthesis and vitamin A is trapped in the liver
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Zn deficiency and Vit A
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impaired retinoic acid synthesis and impaired RAR fxn
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Vitamin D and Vit A
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vitamin D receptor blocks RA action because it can form heterodimers too
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dietary requirement for Vit A
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male/female: 900/700 RAE
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Animal sources of Vit A
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liver, organ meats, egg, dairy products, fish liver oil
these are high in retinyl esters but low in beta carotene |
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plant sources of Vit A
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deep yellow/orange/green vegetables: carrots, sweet potatoes, apricots, broccoli, red palm oil
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Serum retinol levels that lead to deficiency
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>30 micrograms/dl- adequate
10-30 marginal <10 deficient |
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Dark adaptation time and retinol levels
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~5 min normal
>15 deficient |
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are patients with liver disease more sensitive to deficiency or excess of vitamin A?
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yes
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where is Vit A deficiency an endemic? and where?
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yes and southeast asia and africa
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how do you measure vitamin A status?
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liver biospy
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Golden rice is supplemented with what type of Vit A?
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beta carotene
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What is the plant form of Vit D? and what does it get transformed to?
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Ergosterol (provitamin D)--(UV light)--> ergocalciferol (vit D2)
This form is more frequent in supplement and is more potent in rats |
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What is the animal form of Vit D and what does it get transformed to?
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7-dehydrocholesterol (provitamin D) --(UV light)-->cholecalciferol (vit D3)
more present in the diet and more potent in chicken |
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do the animal and plant forms have the same potency in human?
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they have equal potency
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Is vitamin D a vitamin or prohormone?
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the vitamin deficiency can be corrected by rare foods but it is more a prohormone becuase it is synthesized by the skin by a photochemical process and it acts as a hormone on multiple parts of the body
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how many minutes in the summer will make the RDA of Vit D?
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10 minutes on the hands and face
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what is the RDA value for Vit D?
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10 micrograms or 400 IU
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Whats the deal with Vit D in the elderly and babies?
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1. children are born with a 9 month storage
2. Reduced in the elderly, pigmented skin also- any sunscreen blocks vit D synthesis |
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What is the "hinge" element and Vit D?
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its a length of nucleotides that differs for each hormone
Vit D=3 PTH=4 |
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what is the definition of rickets?
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insufficient supply of Ca and P to bone mineralization site Bowed legs, enlarged head and joints, and abnormal rib cage
two types |
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Vit D dependency Rickets Type 1
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children with this type of rickets despite normal Vit D intake because there is a deficient 1aplha-hydroxylation so there is a lack of the active form of Vit D (1,25 dihydoxy D3)
Treatment: 1 microgram of active form of vit D3 |
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Vit D dependency Rickets Type 2
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this is the more serious of rickets, it is caused by a defective (mutated) 1,25 (OH)2D3 receptor gene 9could the Zinc finger or hormone binding domain)
This form is resistant to treatment of the active form of Vit D3 Treatment: Ca and P infusions corrects mineralization and other fxns of vit D remain unsatisfied |
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What is renal osteodystrophy?
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You lose function of the kidneys and then secondary hyperthyroidism so you make large quantities of PTH and then they experienced a marked bone resorption
Treatment: Active form of suppressed PTH expression and Calcium Carbonate to bind P in intestine |
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what is the link b/n osteoporosis, estrogen, and Vit D?
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It may be an estrogen deficiency disorder and the FDA approved a treatment by adding estrogen in women
this all may be due to a 1aplha-hydroxylase defective |
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Psoriasis and Vit D?
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Psoriasis is an autoimmune disorder that causes painful itching and flacking of the skin
Vit D: can be immunosuppressive at pharmacologic doses and redirects skin cell differentiation. it is now being tested as a topical skin cream |
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Atherosclerosis and Vit D
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with hypervitaminosis of Vit D can causes symptoms of atherosclerosis and increases Ca deposits which then damages elastic tissue and smooth muscle tissue of the heart and vessels
this is independent of Cholesterol intake |
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How does melanin effect Vit D?
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Tyr--(UV)-->Melanin--> lower Vit D synthesis in the skin because melanin is a natural sunscreen
melanin is a darker pigment of skin.. |
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Who is at risk for a Vit D deficiency?
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1. Pt's with fat malabsorption
2. Pt with renal disease bc can't form active form of Vit D3 3. Pt with cirrhosis of the liver bc can't form 25-OH-D3 4. pt who aren't in the sun (darker infants in winter in northern latitudes, elderly, & women who are totally covered because of religion) |
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Is Vit D toxic?
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yes, extremely bc its a steriod hormone that is unregulated by the liver
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What are the symptoms of Vit D toxicity in adults?
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1. N&V
2. HTN 3. Mental confusion 4. Ca deposition and damage to heart and kidneys symptoms relate to hypercalcemia (serum Ca>12mg/dl) |
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What are the symptoms of Vit D toxicity in fetus/infants?
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1. mental retardation bc of premature skull calcification
2. narrowing of major blood vessels 3. Ca deposition in a variety of tissues and cell death |
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Lead toxicity and Vit D? what the?
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lead and Ca share teh same intestinal transport system, adn becuase they do vit D can incr lead absorption from the diet, it would be no big deal because it would be stored in bone but vit D also mobilizes ca and lead from the bone matrix leading to lead toxicity
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what is the treatment for Vit D toxicity?
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1. glucocorticoids that compete/antagonize Vit D at the gene level
2. calcitonin with lowers plasma ca |
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what are the AI for different age groups?
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0-50 yrs: 5 micrograms /day
51-70 yrs: 10 71+: 15 1 microgram = 40IU |
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what are the tolerable upper intake levels?
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0-1 yrs- 25
1 yrs +: 50 (10x's the AI) |
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What are dietary sources of Vit D?
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cod liver oil, unfortified milk, fortified milk, fortified cereal, fatty fish and eggs yolks, sunlight
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what are low in Vit D or have none?
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skeletal muscle and meats are low in Vit D and plants have none
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What are some Vit E deficiency symptoms?
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1. rat fetal reabsorption
2.muscular dystrophy 3. hemolysis 4. encephalomalacia |
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what is the difference in structure between tocopherols and tocotrienols?
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tocopherols have saturated bonds on the tails and tocotrienols have 3 unsaturated bonds
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what is within each class of the eight isomers of vit E?
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they have a various number of methyl groups with a chroman ring, the orientation of the 3 chiral carbons at 2,4, and 8 prime
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what are the natural and synthetic forms of vit E?
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1. Natural- RRR-alpha tocopherol (d-alpha-tocopherol)
2. Synthetic- all-rac-alpha-tocopherol which has 8 isomers in the supplement (d,l,alpha-tocopherol) |
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which form natural or synthetic is more biologically active?
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natural, RRR-alpha-tocopherol
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describe some characteristics of vit E supplements?
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they contain alpha-tocopherol esters actate, succinate, nicotinate that prevent vit E oxidation which prolong the shelf life. The supplements are hydrolyzed in the gut by pancreatic esterase and absorbed in the unesterified form
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is there an intestinal transfer protein for vit E?
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nope
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what is the absorption rate of Vit e and that is the preferred order of absorption?
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The rate is low, 15-45%, and alpha-tocotrienol (T3) is preferentially absorbed with gamma or delta T3s and alpha-tocopherol
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Which organ discriminated vit E and how?
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the liver discriminates and it preferentially secretes RRR-alpha tocopherol
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where is most of the alpha tocopherol in the body?
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>90% is in teh adipose tissue, main in fat droplets, not memebranes!!
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where in the body is there fast and slow vit E turnover?
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fast- RBC, liver, spleen
slow- heart, muscle, nerves |
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what is the deal with alpha-tocopherol transfer protein and where is it located?
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- it is found only in hepatocytes and it transfers alpha tocopherol into the VLDL so it in turn regulates the plasma level of Vit E
-it's affinity for the isomers of vit E ranges |
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what are the affinities for the isomers of vit E by alpha-tocopherol transfer protein?
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100% alpha tocopherol
38% beta tocopherol 9% gamma tocopherol 2% delta tocopherol 11% SRR-alpha tocopherol 12% alpha tocotrienol |
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where does excretion of vit e primarily occur?
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in the feces, sometimes in the urine
there is some evidence of excretion in skin |
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what is the fxn of Vit E?
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antioixdant!
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what are some other fxns of Vit E?
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1. gamma tocotrienol enhances the degradation of HMG CoA reductase hypocholesterolemic
2. alpha-tocopherol inhibits protein kinase C activity (glucagon breakdown pathway) |
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what is a reactive oxygen molecule?
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free radical or a single oxygen
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what are the natural ways free radicals are formed?
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1. immunity: phagocytic cells make FRs as they attack invading cells
2. exercise; high oxygen flow damages muscle and o2 reacts with FR |
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what are some of the ways that free radicals damage the body?
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1. denature proteins
2. damage nucleic acids, gene mutation, CA initiation 3. saturate double bonds of FAs in lipid membrane which alters membrane structure and fxn 4. oxidize cholesterol, trigger arterial plaque formation, cause CVD |
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the body's defense system against free radicals are?
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1. mineral-dependent enzymes
2. antioxidants |
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what are the mineral-dependent enzymes and what are their minerals of need?
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1. superoxide dismutase (SOD) with is copper and zinc dependent: it turns superoxide (O2) into hydrogen peroxide (h2O2)
2. Glutathione peroxidase which is Selenium dependent and it turns hydrogen peroxide into water 3. catalase which is iron dependent and also turns hydrogen peroxide into water |
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what are the small molecules that act as antioxidants in the body?
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vitamin C
glutathione uric acid carotenoids vit E |
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what are free radical enzymes?
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1. cytochrome P450: which is iron depdendent, uses superoxide for hydroxylation
2. xanthine oxidase which makse uric acid and superoxide |
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does biological activity equal antioxidant activity?
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no
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what is the biological activity parallel antioxidant activity order?
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alpha>beta>gamma> delta tocopherol
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which biological and antioxidant activity does NOT parallel?
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1. Bio activity: alpha-tocopherol is 3x's alpha-tocotrienol
2. Antioxidant activity: alpha-tocopherol< alpha-tocotrienol |
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Causes of deficiency of Vit E
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1. genetic defect of alpha-TTP
2. genetic defect in lipoprotein synthesis (apoprotein B) |
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what are the two ways that one can have a genetic defect of apo B synthesis?
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1. homozygous hypobetalipoproteinemia: defective apo-B and rapid lipoprotein turnover
2. Abetalipoproteinemia: defective microsomal triacylglycerol transfer protein (MTP) so it can't get to the cell membrance and a defective lipidation of apo-B SO there si no apoB containing lipoprotein and impaired CM secretion |
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what are the 3 secondary to fat malabsorption syndromes?
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1. impaired bile secretion
2. impaired pancreatic digestive enzymes 3. total parental nutrition |
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what are the symptoms of vit E deficiency in animals?
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-necrotizing myopathy
-fetal death and resorption -anemia (hemolytic) -lipofuscin accumulation |
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what are the symptoms of vit E deficiency in humans?
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peripheral neuropathy and RBC hemolysis (hemolytic anemia)
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what are some sources of RRR-alpha-tocopherol?
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wheat germ
safflower sunflower cottonseed palm |
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what are some sources of gamma-tocopherol?
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soybean
corn cottonseed palm |
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what percentages of the total vit E activity belong to which isomers?
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75% RRR-alpha tocopherol
10% gamma-tocopherol |
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what is the RDA for Vit e?
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15 mg of RRR-alpha-tocopherol or equivalents
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one IU= ?? (vit E)
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i mg all-rac-alpha-tocopherol (synthetic form)
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what are the 3 forms of Vit K?
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1. Phylloquinone from plants Vit K1
2.Menaquinone from bacteria Vit K2 3. Menadione from synthetic Vit K3 |
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what is the Vit K absorption?
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- there is both active and passive abs in the intestine, and it's moderately efficient ,10-80% and its highly dependent on adequate fat intake, bile salts and pancreatic juice and carried by chylomicron from intestine to the liver
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What is special is so special about the half life of Vit K?
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- its incredibly short, 2.5 hours
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what is the body pool size?
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.22 millimol SMALL because it's excreted very quickly
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where is vit K located in the body?
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75% in bones
25% in the liver and other tissues containing gamma-glutamyl carboxylases |
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vitamin K is important for the synthesis of what precursor of proteins?
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gamma-glutamic acid GLA
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GLA is important for..
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Ca-binding proteins
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example of Ca-binding proteins are?
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1. Koagulation proteins
2. bone proteins 3.kidney gla proteins |
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tell some crap about koagulation proteins
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there are four blood clotting factors, like II (prothrombin), VII, IX, X
there are also homeostasis proteins C,S,Z,M |
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what does gamma-glutamyl carboxylase do?
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its the enzyme that catalyzes the rxn that adds the extra COO- to glutamic acid so it can bind calcium
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tocotrienols and menaquinones are what kind of molcule?
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mixed isoprenoids
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tocotrienols act as a mixed isopreniods to do what three fxns?
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1.increase degradation of HMG-CoA reductase
2. hypocholesterolemic 3. tumor-suppressive |
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menaquinone acts as a mized isprenoid to do what?
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1. leukemia-suppressive
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Is primary deficiency common?
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nope, vitamin K recycling and menaquinone is synthesized from microbiologic flora of the normal gut
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what is the kind of deficiency that is common with Vit K?
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secondary deficiency
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secondary deficiency can happen 7 ways..
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1. TPN
2.Drugs 3. malabsorption syndrome (GI disorders) 4. PEM-hypothrombinemia 5.liver disease (defective RER and hypothrombinemia) 6. genetics (gamma-glutamyl carboxylase) 7.newborn-hemorrhagic disease of the newborn |
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what is the deal with hemorrhagic disease of the newborn (HDN)?
|
there is poor transmission of lipids to placenta so the neonatal liver is immature in prothrombin synthesis. since breastmilk is low in vit K and the gut is sterile the first few days of life- so they give a 0.5-1.0 mg of vit K injection shortly shortly after birth
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what is the vit K?
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1.0 micrograms/kg/day and it is also helped by enteric bacteria of the intestine
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what is the average intake of vit K?
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300-500 micrograms/gay
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Vit K toxicity?
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menadione only and in infants is causes hemolytic anemia, hpyeralbuminemia, kernicterus (bilirubin encephalopathy)
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sources of vit K
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leafy green vegetables, vegetables (soybean, cottonseed, canola, olive)
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sources of phylloquinone
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animal and plant foods, tabacco
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sources of menaquinone
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liver and cheese
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