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159 Cards in this Set

  • Front
  • Back
basic definition of a vitamin
-organic compound required by the diet in small amounts
-not oxidized to provide energy
-not for structured purposes, but as cofactors
Pyruvate dehydrogenase has five cofactors. what are they?
1. thiamin
2. riboflavin
3. niacin
4. pantothenic acid
5. lipoic acid
what cofactors are needed for alpha ketoglutarate dehydrogenase?
same as pyruvate dehydrogenase
1. thiamin
2. riboflavin
3. niacin
4. pantothenic acid
5. lipoic acid
what enzyme converts pyruvate to acetyl coA?
pyruvate dehydrogenase
what enzyme Alpha-KG to succinyl CoA?
alpha KG dehydrogenase
Some characteristics of fat-soluble vitamins?
-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
water soluble vitamins
-thiamin
-niacin
-B12
-biotin
-ascorbic acid
-riboflavin
-b6
-folate
-pantothenic acid
cofactor
-chemicals required for enzymes ex. coenzyme, metal ion, lipid
coenzyme
small organic molecules required by enzymes

-NOT METAL
holoenzyme
an enzyme with its cofactors
apoenzyme
an enzyme without it's cofactors
mole
contains Avogados number of molecules, (6.02*10^23) and contains a mass in grams=molecular weight
1 molar =?
180 g/L
Vitamin A: two forms
retinoids and carotenoids

-carotenoids: broadest term and ~10% have the ability to be converted to Vit A and retinoids
what are the prohormone forms of vitamin A ?
B-carotene (plant)
all-trans-retinol (animal)
what is the plant version of vitamin a?
b carotene
what is the animal version of vitamin a?
all-trans-retinol
what is the alcohol form of vitamin a?
retinol or all-trans-retinol
what is the aldehyde form of vitamin a & what is it's specialty?
11-cis-retinal and it's a visual cofactor
what is the acid form of vitamin A? What is its purpose in the body?
1. all-trans-retinoic acid and it's derivatives
2. 9-cis-retinoic acid
3. 13-cis-retinoic acid

purpose- active hormone
what is special about the acid form of vitamin a?
the double bonds gives a lot of forms with differ biological activities and affinities for certain receptors
Storage of Vitamin A
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
is vitamin a recycled?
vitamin a is not recycled in lipoproteins (not present abundantly in VLDL)
what kind of cell is vitamin a stored in?
stellate cells until released by an unknown signal and is coupled by other transporters
Ligands
1. flat/planar structures
2. aromatic ring/conjugated double bonds
3. share receptors
4. hydrophobic
5. no cell membrane receptor (into cell by itself)
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)?
1. Cholesterol derivatives: vit D, estrogen, progesterone, testoterone, glucocorticoids, mineralcorticoids

2. NON-cholesterol derivatives: vit A, thyroid hormone, ecdysone
which one of the ligand has a nuclear receptors?
vit D
Zinc fingers are rich in what kind of protein?
cysteine
what dimerize the two ligands together on the retinoic acid receptor?
leucine zipper- it puts two of the receptors together
do plants synthesize vit A?
yes
Steroid receptor superfamily
- 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'
vitamin a affects almost every cell type- how?
it affects the differentiation and proliferation of almost every cell type by controlling transcription of target genes
how does vitamin A effect c-fos & c-jun?
transcription factors in many cells, antagonized by RA-RAR
how does vitamin A effect osteonectin?
regulates chondrocyte (cartilage cell) differentiation and matrix formation
how does vitamin A effect collagenase?
degrades the collagen bone matrix, turned off by RA
how does vitamin A effect homeotic selector genes?
transcription factors that control identity of embryonic structures as they are formed
how does vitamin A effect alcohol dehydrogenase?
turned on by RA
how does vitamin A effect apolipoprotein A1?
turned on by RA
What is the main function of vitamin A?
protein synthesis and cell differentiation
Promotes differentiation of what two types of cells?
1. epithelial cells
2. goblet cells
how does vitamin A promote differentiation of epithelial cells?
1. inside: mucous membranes, linings of the mouth, stomach, intestines, lungs, urinary bladder; vagina, eyelids, sinus pathways

2. outside: skin
RA analogs are used for what?
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)
Retinoic acid containing accutane and isotretinoin are used for what?
epithelial disorders
- severe cystic acne: redifferentiates the sebaceus glands
-psoriasis (autoimmune disorders): RA effects skin, immune system, Vit D
-antiwrinkle cream
do goblet cells stop differentiating without Vit A?
yes
The relationship with vitamin A and immune fxn?
-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
Reproduction and growth and it's relationship with Vit A
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
Isotretinoin syndrome
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
teratogenic doses of Retinoic acid
0.5-1.5 mg/kg/bw

toxic to embryos
what is the link of vitamin A and Fetal ETOH syndrome?
it might be caused by an abnormal vit A metabolism
b carotene is defined as not a pro but a..
antioxidant
what is the link b/n carotenoids and cancer?
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
Eye function and Vit A
maintenance of the cornea of the eye
bitot's spot?
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
Vit A deficiency is the leading cause of what in the world?
blindness

and night blindness
what part of the eye uses Vit A and what kind?
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
the visual cycle is independent of?
the hormonal action of RA and the epithelial corneal differentiation by RA
Toxicity of Vit A
-teratogenicity (toxic to fetus)
-acute peeling, cracking, drying and redness of skin
-clinical hypothyroidism
-death
are carotenoids toxic?
generally no
why does toxicity of vit A cause clinical hypothyroidism?
competition b/n Vit A and thyroid hormone at the receptors, which overwhelm the thyroid gland and get a deficiency of thyroid hormone
is body growth affected by vit A deficiency?
yes, there is a lack
what are some confounding problems that would aggravate Vit A deficiency?
1. measles
2. PEM- Kwashiorkor
3. Zn deficiency
4. Diarrhea and/or parasitic infection
5. Vit D toxicity
Measles and vit A
-depletes the liver stores of vit A which worses vit A deficiency by an unknown mechanism

-major health problem in non-industrialized nations
PEM (Kwashiorkor) and Vit A
insufficient RBP synthesis and vitamin A is trapped in the liver
Zn deficiency and Vit A
impaired retinoic acid synthesis and impaired RAR fxn
Vitamin D and Vit A
vitamin D receptor blocks RA action because it can form heterodimers too
dietary requirement for Vit A
male/female: 900/700 RAE
Animal sources of Vit A
liver, organ meats, egg, dairy products, fish liver oil

these are high in retinyl esters but low in beta carotene
plant sources of Vit A
deep yellow/orange/green vegetables: carrots, sweet potatoes, apricots, broccoli, red palm oil
Serum retinol levels that lead to deficiency
>30 micrograms/dl- adequate
10-30 marginal
<10 deficient
Dark adaptation time and retinol levels
~5 min normal
>15 deficient
are patients with liver disease more sensitive to deficiency or excess of vitamin A?
yes
where is Vit A deficiency an endemic? and where?
yes and southeast asia and africa
how do you measure vitamin A status?
liver biospy
Golden rice is supplemented with what type of Vit A?
beta carotene
What is the plant form of Vit D? and what does it get transformed to?
Ergosterol (provitamin D)--(UV light)--> ergocalciferol (vit D2)

This form is more frequent in supplement and is more potent in rats
What is the animal form of Vit D and what does it get transformed to?
7-dehydrocholesterol (provitamin D) --(UV light)-->cholecalciferol (vit D3)

more present in the diet and more potent in chicken
do the animal and plant forms have the same potency in human?
they have equal potency
Is vitamin D a vitamin or prohormone?
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
how many minutes in the summer will make the RDA of Vit D?
10 minutes on the hands and face
what is the RDA value for Vit D?
10 micrograms or 400 IU
Whats the deal with Vit D in the elderly and babies?
1. children are born with a 9 month storage
2. Reduced in the elderly, pigmented skin

also- any sunscreen blocks vit D synthesis
What is the "hinge" element and Vit D?
its a length of nucleotides that differs for each hormone

Vit D=3
PTH=4
what is the definition of rickets?
insufficient supply of Ca and P to bone mineralization site Bowed legs, enlarged head and joints, and abnormal rib cage

two types
Vit D dependency Rickets Type 1
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
Vit D dependency Rickets Type 2
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
What is renal osteodystrophy?
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
what is the link b/n osteoporosis, estrogen, and Vit D?
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
Psoriasis and Vit D?
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
Atherosclerosis and Vit D
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
How does melanin effect Vit D?
Tyr--(UV)-->Melanin--> lower Vit D synthesis in the skin because melanin is a natural sunscreen

melanin is a darker pigment of skin..
Who is at risk for a Vit D deficiency?
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)
Is Vit D toxic?
yes, extremely bc its a steriod hormone that is unregulated by the liver
What are the symptoms of Vit D toxicity in adults?
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)
What are the symptoms of Vit D toxicity in fetus/infants?
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
Lead toxicity and Vit D? what the?
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
what is the treatment for Vit D toxicity?
1. glucocorticoids that compete/antagonize Vit D at the gene level
2. calcitonin with lowers plasma ca
what are the AI for different age groups?
0-50 yrs: 5 micrograms /day
51-70 yrs: 10
71+: 15

1 microgram = 40IU
what are the tolerable upper intake levels?
0-1 yrs- 25
1 yrs +: 50 (10x's the AI)
What are dietary sources of Vit D?
cod liver oil, unfortified milk, fortified milk, fortified cereal, fatty fish and eggs yolks, sunlight
what are low in Vit D or have none?
skeletal muscle and meats are low in Vit D and plants have none
What are some Vit E deficiency symptoms?
1. rat fetal reabsorption
2.muscular dystrophy
3. hemolysis
4. encephalomalacia
what is the difference in structure between tocopherols and tocotrienols?
tocopherols have saturated bonds on the tails and tocotrienols have 3 unsaturated bonds
what is within each class of the eight isomers of vit E?
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
what are the natural and synthetic forms of vit E?
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)
which form natural or synthetic is more biologically active?
natural, RRR-alpha-tocopherol
describe some characteristics of vit E supplements?
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
is there an intestinal transfer protein for vit E?
nope
what is the absorption rate of Vit e and that is the preferred order of absorption?
The rate is low, 15-45%, and alpha-tocotrienol (T3) is preferentially absorbed with gamma or delta T3s and alpha-tocopherol
Which organ discriminated vit E and how?
the liver discriminates and it preferentially secretes RRR-alpha tocopherol
where is most of the alpha tocopherol in the body?
>90% is in teh adipose tissue, main in fat droplets, not memebranes!!
where in the body is there fast and slow vit E turnover?
fast- RBC, liver, spleen
slow- heart, muscle, nerves
what is the deal with alpha-tocopherol transfer protein and where is it located?
- 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
what are the affinities for the isomers of vit E by alpha-tocopherol transfer protein?
100% alpha tocopherol
38% beta tocopherol
9% gamma tocopherol
2% delta tocopherol
11% SRR-alpha tocopherol
12% alpha tocotrienol
where does excretion of vit e primarily occur?
in the feces, sometimes in the urine

there is some evidence of excretion in skin
what is the fxn of Vit E?
antioixdant!
what are some other fxns of Vit E?
1. gamma tocotrienol enhances the degradation of HMG CoA reductase hypocholesterolemic

2. alpha-tocopherol inhibits protein kinase C activity (glucagon breakdown pathway)
what is a reactive oxygen molecule?
free radical or a single oxygen
what are the natural ways free radicals are formed?
1. immunity: phagocytic cells make FRs as they attack invading cells
2. exercise; high oxygen flow damages muscle and o2 reacts with FR
what are some of the ways that free radicals damage the body?
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
the body's defense system against free radicals are?
1. mineral-dependent enzymes
2. antioxidants
what are the mineral-dependent enzymes and what are their minerals of need?
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
what are the small molecules that act as antioxidants in the body?
vitamin C
glutathione
uric acid
carotenoids
vit E
what are free radical enzymes?
1. cytochrome P450: which is iron depdendent, uses superoxide for hydroxylation

2. xanthine oxidase which makse uric acid and superoxide
does biological activity equal antioxidant activity?
no
what is the biological activity parallel antioxidant activity order?
alpha>beta>gamma> delta tocopherol
which biological and antioxidant activity does NOT parallel?
1. Bio activity: alpha-tocopherol is 3x's alpha-tocotrienol

2. Antioxidant activity: alpha-tocopherol< alpha-tocotrienol
Causes of deficiency of Vit E
1. genetic defect of alpha-TTP
2. genetic defect in lipoprotein synthesis (apoprotein B)
what are the two ways that one can have a genetic defect of apo B synthesis?
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
what are the 3 secondary to fat malabsorption syndromes?
1. impaired bile secretion
2. impaired pancreatic digestive enzymes
3. total parental nutrition
what are the symptoms of vit E deficiency in animals?
-necrotizing myopathy
-fetal death and resorption
-anemia (hemolytic)
-lipofuscin accumulation
what are the symptoms of vit E deficiency in humans?
peripheral neuropathy and RBC hemolysis (hemolytic anemia)
what are some sources of RRR-alpha-tocopherol?
wheat germ
safflower
sunflower
cottonseed
palm
what are some sources of gamma-tocopherol?
soybean
corn
cottonseed
palm
what percentages of the total vit E activity belong to which isomers?
75% RRR-alpha tocopherol
10% gamma-tocopherol
what is the RDA for Vit e?
15 mg of RRR-alpha-tocopherol or equivalents
one IU= ?? (vit E)
i mg all-rac-alpha-tocopherol (synthetic form)
what are the 3 forms of Vit K?
1. Phylloquinone from plants Vit K1

2.Menaquinone from bacteria Vit K2

3. Menadione from synthetic Vit K3
what is the Vit K absorption?
- 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
What is special is so special about the half life of Vit K?
- its incredibly short, 2.5 hours
what is the body pool size?
.22 millimol SMALL because it's excreted very quickly
where is vit K located in the body?
75% in bones
25% in the liver
and other tissues containing gamma-glutamyl carboxylases
vitamin K is important for the synthesis of what precursor of proteins?
gamma-glutamic acid GLA
GLA is important for..
Ca-binding proteins
example of Ca-binding proteins are?
1. Koagulation proteins
2. bone proteins
3.kidney gla proteins
tell some crap about koagulation proteins
there are four blood clotting factors, like II (prothrombin), VII, IX, X

there are also homeostasis proteins C,S,Z,M
what does gamma-glutamyl carboxylase do?
its the enzyme that catalyzes the rxn that adds the extra COO- to glutamic acid so it can bind calcium
tocotrienols and menaquinones are what kind of molcule?
mixed isoprenoids
tocotrienols act as a mixed isopreniods to do what three fxns?
1.increase degradation of HMG-CoA reductase
2. hypocholesterolemic
3. tumor-suppressive
menaquinone acts as a mized isprenoid to do what?
1. leukemia-suppressive
Is primary deficiency common?
nope, vitamin K recycling and menaquinone is synthesized from microbiologic flora of the normal gut
what is the kind of deficiency that is common with Vit K?
secondary deficiency
secondary deficiency can happen 7 ways..
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
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
what is the vit K?
1.0 micrograms/kg/day and it is also helped by enteric bacteria of the intestine
what is the average intake of vit K?
300-500 micrograms/gay
Vit K toxicity?
menadione only and in infants is causes hemolytic anemia, hpyeralbuminemia, kernicterus (bilirubin encephalopathy)
sources of vit K
leafy green vegetables, vegetables (soybean, cottonseed, canola, olive)
sources of phylloquinone
animal and plant foods, tabacco
sources of menaquinone
liver and cheese