Vitamins

Question 1

Fat soluble vitamins?

Answer 1

A (retinol, B-carotene), D (cholecalciterol), E (tocopherols), K (phylloquinones, menaquinones)

Question 2

Water soluble vitamins from non-B complex

Answer 2

C (ascorbic acid)

Question 3

water soluble vitamins from B complex that are energy-releasing

Answer 3

B1 (thiamine), B2 (riboflavin), B3 (niacin), biotin, pantothenic acid

Question 4

water soluble vitamins from B complex that are hematopoetic

Answer 4

folic acid, B12

Question 5

water soluble vitamins from B complex that are neither energy releasing nor hematopoetic

Answer 5

B6 (pyridoxine), pyrodoxial, pyridoxamine

Question 6

Vitamins involved with blood formaiton and clotting

Answer 6

B6, B12, Folate, K

Question 7

Vitamins involved with protein and AA metabolism

Answer 7

B6, Folate, B12, C, choline (not a true vitamin), riboflavin (indirectly)

Question 8

Vitamins involved with antioxidant defenses

Answer 8

E, C (likely), Carotenoids, riboflavin (indirect)

Question 9

Vitamins involved with gene expression

Answer 9

A, D

Question 10

Vitamins involved with bone health

Answer 10

A, D, K, C

Question 11

Vitamins involved with energy metabolism

Answer 11

thiamin, riboflavin, niacin, pantothenic acid, biotin, B12

Question 12

bio- in terms of vitamins

Answer 12

how much of the vitamin actually gets into us and is activated?

Question 13

Facts about many vitamins

Answer 13

1. hydrolyzed in stomach and are released from protein complexes in food
2. most are absorbed in upper small intestine. B12 is the only exception (absorbed in ileum)
3. water soluble vitamins are absorbed directly into portal vein, transported to liver, and are stored (B12) or sent out in circulation
4. Excess water soluble vitamins are excreted through kidneys in urine

Question 14

describe absorption process of fat-soluble vitamins

Answer 14

absorbed with monoglycerides and FAs.
1. mixed micelle in the intestinal lumen, containing FA, cholesterol, D, A, E, K)
2. repackaged in chylomicrons
3. chylomicron sent to lymphatics before entering blood
Note: the fats do not go directly into portal circulation because chylomicron is too large
Note: requires bile salts

Question 15

What are all the forms of vitamin A?

Answer 15

1. Retinol (active form, comes from retinyl esters and animal foods)
2. retinal (note, spelt with a, not o), which converts to retinoic acid
3. Beta-carotene (the fused form of retinal and retinol). found in plant foods and supplements. has alternating singular and double bonds, which is why it is colored!!! IN this case, plant foods that are red, orange, and yellow

Question 16

what is a retinol activity equivalent (Rae)?

Answer 16

Note: you can eat b-carotene and get retinol. Specifically, 12 micrograms of B-carotene will yield 1 microgram of retinol.

Question 17

Functions of vitamin A

Answer 17

1. Vision ( Essential for seeing black and white (“rod” cells in retina)
    Particularly important for night vision and recovery of sight after a
   flash of bright light (like snow-blindness))
2. Cell differentiation ( Process by which a new cell turns into its “destined” form
    Important for the maturing of “epithelial cells”, such as those in the intestine and skin (in deficient state, the skin is highly effected)
    Important for the development of the embryo into a fully formed
   organism
    Important synthesis of lymphocytes and antibodies (immune
   function)
    Bone health
    Protection against cancer?)

Question 18

how does vitamin A affect vision?

Answer 18

1. Light shines through to retina
2. within retina are rods and cones. the light hits the rods to affect rhodopsin (combo of opsin and cis-retinal)
3. when light hits cis-retinal, it converts to trans-retinal, separating trans-retinal from opsin.
4. the trans-retinal is converts to cis-retinal and retinoic acid. the opsin combines back with the cis-retinal to form og rhodopsin molecule.
   Note: the splitting step is important for brain so see.

Question 19

how does vitamin A affect cell differentiation?

Answer 19

immature cell + vitamin A = differentiation cell –> could become any cell based on location. Really important for digestional tract, as in example it became intestinal cell.

Question 20

What happens if you are vitamin A deficient? Who are susceptible?

Answer 20

All of these disorders are more common in developing countries
Mild deficiency: night blindness
Severe forms are xerophthalmia (damage to cornea, dry eyes, scarring, and blindness)
and hyperkeratosis (increased keratin synth in skin and nails) as well as infections.

Question 21

What can be done to prevent Vitamin A deficiency?

Answer 21

GMOs. Example: genetically modified rice what synthesizes B-carotene.

Question 22

What are the 2 forms of vitamin D?

Answer 22

1. D2 (ergocalciferol) (methyl + double bond)
2. D3 (cholecalciferol) (nothing)
   Both structures look like cholesterol

Question 23

How do you make vitamin D?

Answer 23

1. UV rays from sun hit skin, specifically 7-deydrocholesterol to convert it to cholecalciferol (D3).
2. D3 (from skin, or from diet…fish + meat) along with D2 (from diet only…supplements) are sent to liver, which produces 25-hydroxyvitamin D3.
3. 25-hydroxyvitamin D3 is sent to kidney, which makes 1,25-dihydroxyvitamin D3 (aka calcitriol). Calcitriol = active form.
   Note: 1,25-dihydroxyvitamin D3 maintains Ca balance in body

Question 24

What factors affect D3 synth?

Answer 24

 Overcast skies
 Smog
 Dark skin (melanin)
 Angle of sunlight (winter)
 Sunscreen
 Age

Question 25

What are the functions of vitamin D?

Answer 25

1. Ca homeostasis ( Increases calcium absorption and bioavailability  Decreases calcium excretion by the kidneys (urine)  Increased calcium release from bones) 2. Gene expression and cell differentiation (like Vitamin A) through vitamin D receptor

Question 26

How does vitamin D help with Ca absorption and bioavailability?

Answer 26

1. 1,25(OH)2D3 (calcitriol) enters enterocytes and binds to vitamin D receptor (cytosol receptor). 2. Cytosol sends calcitriol to nucleus 3. nuc causes gene expression, which causes production of Ca Binding Protein 4. Calcium binding protein binds Ca that was absorbed from diet. 5. Ca binding protein + Ca from diet leave enterocyte together and travel to rest of body Note: consuming high levels of Ca will causes Ca to just passively enter basolateral side through paracellular pathway.

Question 27

How does vitamin maintain Ca homeostasis?

Answer 27

1. If Ca starts to rise, signal is sent to thyroid, which releases calcitonin, which tells kidneys to reduce Ca uptake and tells bones to deposit Ca to the bones. Homeostasis obtained. 2. If stimulus shows a drop in Ca, signal goes to parathyroid gland and tells it to secrete PTH . PTH tells bones to release calcium, tells kidneys to recycle (reabsorb) Ca, and tells kidneys to produce more calcitriol, which goes to intestines to increase Ca uptake. Homeostasis obtained.

Question 28

How does vitamin D affect gene expression

Answer 28

calcitriol, after full synth from liver, enters nucleus and activates vitamin D receptor, which binds to the DNA and activates transcritption. Calcitriol could also bind to vitamin D receptor on the cell membrane surface, which triggers signaling pathways that trigger transcription in the nucleus

Question 29

What happens if you have severe vitamin D deficiency?

Answer 29

1. Rickets (in zeh kiddies, bones are not developing and strengthening. Legs become bow-legged, bending under weight of child) 2. osteopenia (bone density begins to dwindle) and Osteoporosis (more critical loss of bone, which can lead to fractures). between 1 and -2.5 standard deviations = osteopenia. anything less than that = osteoporosis. comparison to other bone densities on the planet 3. 1,25 hydroxylase is found in many cells (converts inactive to active form of vitamin D). Vitamin D is found in almost every cell in the body. Realized it can lead to brain abnormalities is too low. Leads to hyperintensive signal in the periventricular white matter. 4. can also lead to alzheimer's and dementia. All kinds of memory (spacial, executive function, episodic, sensory) all took some kind of L if they were low in vitamin D.

Question 30

What are the forms of vitamin K?

Answer 30

1. K1 Phylloquinone (from plants and supplements). only has single bonds 2. K2 menaquinone (come from bacteria in large intestin) (has alternating single and double bonds) 3. K3 menadione (man-made, "pro-vitamin")

Question 31

What is vitamin K involved with?

Answer 31

Blood clotting (coagulation) 1. inactive clotting factors link with K and Ca to make active clotting factors. 2. the active clotting factors convert prothrombin to thrombin 3. Thrombin converts fibrinogen (water soluble) to fibrin (NOT water soluble), which is the clotting Note: Warfarin (Coumadin) is a blood thinner that works by cutting out vitamin K, inhibiting clotting ability. If overused, patient will bleed out in situations of a cut. Note that warfarin is also used as rat poison, causing the rats to bleed to death.

Question 32

How does vitamin K affect bone calcification?

Answer 32

1. Vitamin D regulates asteocalcin transcription. 2. K catalyzes the reaction 3. Calcium is now allowed to bind to active osteocalcin. 4. end result is hydroxyapatite structure

Question 33

what happens if one is K deficient?

Answer 33

Uncontrollable Bleeding!!!  Rare in adults  More common in newborns  Low vitamin K stores at birth  Little or no bacterial production in large intestine  Low levels of vitamin K in breast milk  All babies given vitamin K injections at birth (to get them through 6 months until they can support their own)  Can occur in children and adults with fat malabsorption diseases, causing deficiencies in ADEK.  Prolonged use of antibiotics kill large intestine bacteria (this tanks K presence)

Question 34

What are the forms of vitamin E?

Answer 34

Most biologically active form is alpha-tocopherol

Question 35

What is the main function of Vitamin E?

Answer 35

Works as an antioxidant!  Protects biological membranes (lipophilic regions) against free radicals  Especially important to tissues exposed to oxygen (e.g. lungs and red blood cells)  Works best in conjunction with vitamin C and selenium (as in E does not work best in isolation. Needs its crew)  Protects DNA from oxidative damage (may reduce risk of cancer)  May protect against cataracts  May protect against heart disease

Question 36

How does vitamin E function?

Answer 36

Oxidant (due to stress, injury, or toxins) at phospholipid membrane interacts with the FA chain on phospholipids, causing oxidation, leading to chain reaction, killing the adjacent FA chains. When it encounters E, the chain reaction stops. This allows the cell to recover and maintain membrane integrity

Question 37

How does Vitamin E interact with vitamin C?

Answer 37

When E takes the free-radical hit, you need to convert that E back to normal. E fixes itself by passing radical off to vitamin C. Vitamin C, through enzymes, removed the free radical.

Question 38

What happens if you are deficient in E?

Answer 38

Hemolytic anemia:  Rare, but occurs in infants fed formula with too little vitamin E, in cystic fibrosis (fat malabsorption disorder)  Weakened and ruptured red blood cells (due to oxidative damage to their phospholipid membranes)...link this to biliruben! You can also think about sickle cell anemia.  Neuromuscular problems, neuromuscular pain, loss of coordination

Question 39

What are the forms of vitamin C (ascorbate, ascorbic acid)

Answer 39

1. L-ascorbic acid (hydroxyls) | 2. L-dehydroascorbic acid (no hydroxyls)

Question 40

What are the functions of C?

Answer 40

1. Antioxidant  Increases absorption and bioavailability  Reduces superoxide (bad oxygen) to hydrogen peroxide (not so bad oxygen) 2. Reduces iron (and copper, and chromium)  Increases absorption and bioavailability  Drink orange juice with fortified cereal 3. Synthesis of important molecules  Carnitine: fatty acid metabolism for energy production  Tyrosine: amino acid  Neurotransmitters: nervous system function  Hormones: particularly digestive hormones  Collagen: required for making skin, muscles, cartilage, tendons, and gums

Question 41

How does C work as an antioxidant?

Answer 41

1. Superoxide anion (O2-) is linked with ascorbic acid (C). C is converts to dehydroascorbic acid and superoxide is converted H2O2. 2. H2O2 is converted to water

Question 42

How does C reduce iron?

Answer 42

Fe3 is converted to Fe2 by using ascorbic acid and converting it to dehydroascorbic acid. This is important for Fe absorption.

Question 43

How does C help with Fe absorption?

Answer 43

1. Heme iron is absorbed (from animals) is more readily absorbed into enterocyte 2. If you insist in getting Fe in through plant sources, you need C, which converts Fe3 to Fe2 through oxidation. Fe2 is the only form that can be absorbed. Problem is that Fe2 is not the best for the enterocyte, so Fe2 is stored in Ferritin. If not stored, it is kicked out through transporter and converted back to Fe3, and bound to transport protein called Transferrin.

Question 44

What happens in C deficiency?

Answer 44

Scurvy! James Lind: British Doctor discovered it.  Cured scurvy with lemons and limes in British sailors (origin of the nickname “limeys”)  Bleeding gums, skin irritation, bruising, poor wound healing

Question 45

Is vitamin C good at preventing colds? When you do get the cold, does it help reduce cold duration?

Answer 45

If patients are in constant cold and stressful environments, then yes, C is effective. If the patient is in normal environments, it does not have a strong effect. Upon getting the cold, C is proven to reduce its duration (10 percent reduction...so, like a day).

Question 46

Which vitamins are involved with ATP?

Answer 46

B1, B2, B3, B5, and B7

Question 47

What are the forms of B1?

Answer 47

1. B1 (thiamin)...supplement form | 2. TPP (thiamin pyrophosphate)...this is the active cofactor form...the form with addition of 2 phosphates.

Question 48

How does B1 get absorbed and made available?

Answer 48

1. B1 gets absorbed with vitamin C. In the presence of oxidants in foods or in the presences of OH, thiamin enterocyte absorption into duodenum or jejunum fails. 2. Thiamin that successfully enters if activated with presence of 2 ATP molecules to become TPP. TPP then flows out to basolateral side and enters blood to get to the liver.

Question 49

What are the functions of B1?

Answer 49

``` 1. ATP production (energy)  Pyruvate to acetyl CoA  Krebs cycle  Pentose-phosphate pathway 2. DNA/RNA synth  Required for enzymes that synthesize DNA and RNA 3. NADPH synth  Required for various functions, including triglyceride synthesis 4. Nerve function  Thiamin Triphosphate (TTP) ```

Question 50

What enzymes in the pentose phosphase, glycolysis, and krebs cycle are B1 involved in?

Answer 50

1. Transketolase in Pentose Phosphate Pathway 2. Pyruvate Dehydrogenase in Glycolysis 3. alpha-ketoglutarate dehydrogenase in

Question 51

What happens if you are deficient in B1?

Answer 51

Beriberi Disease. There are 4 forms: 1. Dry  Severe muscle wasting, leg cramps, tenderness, decreased feeling in feet and toes (peripheral neuropathy) 2. Wet  Swelling (edema) of arms and legs, enlargement of heart, breathing problems, possible heart failure 3. Infantile  Babies breast-fed by thiamin-deficient mothers  Heart failure 4. Cerebral (Wernicke-Korsakoff Syndrome)  Often caused by ALCOHOLISM (low B1 intake + impaired absorption)  Involuntary movement and paralysis of the eye, poor muscle coordination, confusion and short-term memory loss.

Question 52

What happens if you are B1 deficcient?

Answer 52

Correlated to having heart failure.

Question 53

What are the forms of B2 (riboflavin)

Answer 53

1. Riboflavin 2. Flavin mononucleotide (FMN)...Active form since it has a new phosphate group 3. Flavin adenine dinucleotide (FAD)...also Active form since it added yet another phosphate group

Question 54

In Krebs, what produced energy molecule does riboflavin help to produce? How does this affect ATP production?

Answer 54

1. 2 FADH2's 2. The FADPH's are used in ox phos to pump H's into the mitochondrial intermembrane space, which leads to ATP production.

Question 55

What are the functions of B2?

Answer 55

1. Redox reactions (it oxidizes NADPH to NADP+ and converting FAD to FADH2. The FADH2 the oxidizes a substrate, converting itself back to FAD) 2. ATP Production (Energy)  Krebs cycle  Use of fatty acids for energy 3. Synth or activation of Vitamins  Vitamin A, folate, niacin, vitamin B6, vitamin K 4. Neurotransmitter Metabolism  Dopamine, Norepinephrine

Question 56

What happens if one is deficient in B2?

Answer 56

Ariboflavinosis  Isolated deficiency is rare  Generally occurs in instances of malnutrition and multiple micronutrient deficiencies  Muscle weakness, mouth and lip sores (cheilosis), mouth inflammation (stomatitis), enlarged and inflamed tongue (glossitis)  Can occur secondary to alcoholism and thyroid disease. Can also cause glossitis t(tho other vitamin deficiencies also cause this, so this is not a determining factor), and seborrheic dermititis (screws up skin on head, nose, eyes , chest area, naval, crotch area)

Question 57

What is the relationship between B2 and BP?

Answer 57

B2 reduces BP in peoplez with genetic predisposition to high BP. Can legitimately lower it as much as 10 units of BP.

Question 58

What are the forms of B3 (niacin)

Answer 58

1. Niacin (inactive) 2. Nicotinamide (inactive) 3. NAD (nicotinamide adenine dinucleotide)...active form 4 NADP (Nicotinamide adenine dinucleotide phosphate)...active form

Question 59

What AA can be converted to niacin? what other vitamins have alternate ways to be obtained int he body?

Answer 59

tryptophan 2. D can be obtained through sunlight UV reactions on skin. A can be obtained by eating B-carotene. In all 3 cases, the alternative path is not enough to sustain health, so you need all the pathways offered.

Question 60

How does B3 help with ATP production?

Answer 60

It is a cofactor for 2 steps in glycolysis and a cofactor for one step in krebs.

Question 61

What are the functions for B3 (niacin)

Answer 61

1. Redox reactions (it oxidizes NADPH to NADP+ and converting FAD to FADH2. The FADH2 the oxidizes a substrate, converting itself back to FAD) 2. ATP Production (Energy)  Krebs cycle  Use of fatty acids for energy 3. Synth and metabolism of many compounds.  Fatty acids, cholesterol, steroid hormones, DNA, Vitamin C, folate 4. Cholesterol metabolism  Lowers LDL and raises HDL

Question 62

What happens if you are deficient in niacin?

Answer 62

``` Pellagra  Once was very common in the Southern U.S. due to corn being the primary source of protein (corn is low in both niacin and tryptophan)  The 4 “D’s”  Dermatitis  Diarrhea  Dementia  Death ``` Patients with Niacin deficiency are also present with Casal's necklace and bilateral symmetrical rash upon sun exposure

Question 63

How does Niacin (B3) affect cholesterol and TAGs?

Answer 63

Lowers them. However, the side-effect is flushing and itching, which you would treat with aspirin or ibprofen

Question 64

What are the forms of panothenic acid (B5)...Note: pan = everywhere, which describes it's involvement in energy production.

Answer 64

1. Pantothenic acid 2. 4-phosphopentethenine 3. CoEnzyme A (CoA) 4. Acyl carrier Protein (ACP) (carries coenzyme A)

Question 65

What are the functions of B5 (panathonic acid)?

Answer 65

``` 1. ATP production (energy)  Glycolysis  Krebs cycle 2. Synthesis of many compounds  Heme, cholesterol, bile salts, phospholipids, fatty acids, steroid hormones ```

Question 66

What is special about B5's involvement in energy production?

Answer 66

It is is the CoA in acetyl CoA. Which means, B5 is involved in nearly every energy pathway

Question 67

Describe the Biotin (B7) cycle Where is biotin obtained?

Answer 67

1. Biotin is obtained from diet and gut flora (like K) 2. Biotin is involved in the activation of apocarboxylase to make holocarboxylase 3. holocarboxylase is used in protein catabolism, Fa synth, and gluconeogenesis

Question 68

How can biotin (B7)'s bioavailability be affected?

Answer 68

Biotin is typically bound to protein in food; usually does not affect bioavailability much Exception: avidin (found in egg whites)  Very strong binding to biotin, inhibits absorption (the strongest binding to 2 substances in all of biology that we know of)  Only a problem when eggs are eaten raw (uncooked). you would need to cook it.

Question 69

What are the of biotin

Answer 69

``` Carboxylase reactions:  Gluconeogenesis  Protein catabolism  Fatty acid synthesis  ATP Production (acts as a cofactor in conversion of pyruvate to oxaloacetate) ```

Question 70

What happens if one is deficient in biotin?

Answer 70

Not common. But, can be an issue B7, more so in kiddies eating foods lacking :  Daily consumption of a large number of raw eggs  Intestinal diseases that block absorption (e.g. inflammatory bowel disease)  Depression, hallucinations, skin irritation, infections, hair loss, poor muscle control, seizures, developmental delays

Question 71

What is one-carbon metabolism? What enzyme is the simplest to mod and convert to an entirely different enzyme, affecting the direction of the C from serine?

Answer 71

1. Based off folate metabolism 2. Serine IS THE SOURCE of the one carbon. 3. This one carbson leads to synth of THF, methyleneTHF, FormylTHF, and DHF. F = folate. All the folates would be affected. 4. That one carbon is also linked to DNA production, as well as to methionine and its pathways 5. MTHFR is the stated enzyme.

Question 72

how do you convert folic acid to THF?

Answer 72

you reduce it 2x with NADPH

Question 73

What is B6? what does it do?

Answer 73

PLP (active form), responsible of converting serine to glycine

Question 74

What are the 4 important AA in the one-carbon metabolism?

Answer 74

serine, glycine, homocysteine (has sulfur group), and methionine

Question 75

What is transulfuration pathway?

Answer 75

serine + B6 becomes cystathionine. if you add another B6, you get cystein

Question 76

What are the 4 important AA in the one-carbon metabolism?

Answer 76

serine, glycine, homocysteine (has sulfur group), and methionine

Question 77

What are the forms of B6?

Answer 77

1. Pyridoxine (PN)- supplement 2. Pyridoxal 5'-phosphate (PLP) - active cofactor 3. 4-Pyridoxic acid (found in urine)

Question 78

Describe the B6 absorption process

Answer 78

1. Phosphorylated B6 (such as PMP or PLP) encounter hydrolase in the lumen, which dephosphorylates it. 2. Dephosphorylated forms (PN, PNG, PM, PL) can now be absorbed in jejunum. 3. If the enterocyte needs some of the B6, it will re-phos it with a kinase. 4. Remaining unphos forms are sent across basolateral side into blood. 5. Some of the B6 enters RBCs, converted to PLP in the RBC, and stays trapped there (thank the phosphorylation.)

Question 79

List some of the reactions PLP are depended on to run? Note that there are over 100.

Answer 79

``` 1. Transamination  Amino acids to respective keto acids  Ex. Glutamate to α-ketoglutarate 2. Decarboxylations  Elimination of CO2  Ex. L-dopa (neurotranmitter...linked to parkinson's disease when in low quantities, since you would be unable to make dopamine) to dopamine. note, L-dopa does not cross BBB. It Can't. Only dopamine can, which makes treating disease difficult. If you don't have B6, you can't make dopamine, which could lead to this disease 3. Heme synth (first step)  Succinyl CoA + Glycine = δ-Aminolevulinate 4. One-carbon metabolism  Serine-Glycine interconversion  Homocysteine catabolism 5. Lipid and carb metabolism  Sphingolipid synthesis  Muscle glycogen phosphorylase ```

Question 80

Describe the B6 absorption process

Answer 80

1. Phosphorylated B6 (such as PMP or PLP) encounter hydrolase in the lumen, which dephosphorylates it. 2. Dephosphorylated forms (PN, PNG, PM, PL) can now be absorbed in jejunum. 3. If the enterocyte needs some of the B6, it will re-phos it with a kinase. 4. Remaining unphos forms are sent across basolateral side into blood.

Question 81

What is the relationship between PLP and the SChiff Base Formation?

Answer 81

PLP apparently does a shift base reaction with a side chain of an enzyme, allowing for transamination/decarboxylation reactions. PLP then comes off and does it again. Those taking High dose L-dopa for parkinsons have low B6 in circulation and are at risk for being B6 dependent because of the high dose of the drug you have to give. Reason: the L-dopa drug forms a shift base reaction with PLP, locking it up and keeping it from working on anything else. Remember that PLP = B6, and B6 does over 100 reactions in the body....

Question 82

What happens if you are deficient in B6?

Answer 82

1. Microcytic anemia (will look SMALL and EMPTY in pics because there is NO HEME in these RBCs). Note that this is more commonly caused by Fe deficiency  Inhibited heme synthesis 2. Convulusions/EEG abnormalities  Inhibited neurotransmitter synthesis (e.g. serotonin, dopamine)  Accumulation of toxic products of tryptophan metabolism 3 Hyperhomocysteinemia  Inhibited homocysteine catabolism  Increased risk of vascular disease 4. Inflammatory disease (which may be reducing the B6 level)  e.g. inflammatory bowel disease, rheumatoid arthritis  Reduced plasma PLP  Cause or effect? Note that as inflammation increases, B6 status decreases.

Question 83

What are the different forms of folate (folic acid aka B9)? Where does the supplemental part get acted on to become active?

Answer 83

1. supplemental, which contains glutamic acid , para-amino-benzoic acid (PABA)..found in sunscreens and lotions, and 2,4,6-substituted pterin. Gets acted on at 5 and 10 spots to become active. Note that all the active forms are reduced. They are the following: 2.  Tetrahydrofolate (THF) 3.  N5-methyltetrahydrofolate (CH3-THF) 4.  N5,10-methylenetetrahydrofolate (CH2-THF) 5.  N5-formyltetrahydrofolate (CHO-THF) 6.  Dihydrofolate (DHF) 7.  Methotrexate (10-methyl-4-amino-THF)...note that this substitution as at the 4th position instead of the 5th. used for arthritis (and cancer in higher doses)...works because if you block folate, you block DNA synth, which will kill the cancer cell (along with the noncancered cells :/).

Question 84

How do you absorb folate?

Answer 84

1. Folate is thiccc (stacked with a long chain of glutamates). This long chain prevents crossing into the jejunum enterocyte. Solution: GCP-II enzyme, which cuts off the c's (glutamates) until there is only one glutamic acid on the end. 2. Folate enters enterocyte, simaltaneously with H. 3. Cell may convert it to ch3-THF for its own use. It may also sent this ch3-THF out tot eh blood. 4. It could also just go straight through to the basolateral side if given in high enough doses, without being converted to ch3-THF

Question 85

Explain the dietary folate equivalents (DFE) pertaining to folate.

Answer 85

0.5 micrograms folic acid consumed without food. This goes does to 0.6 if eaten with food. This goes down even further if you just eat it directly (like, folate found in food instead of straight up folic acid). Lgtitmately need to eat 2x as much food folate as you would need if you just ate folate acid without food. So, to best absorb folate, you need to eat it as folic acid, and you need to eat it without any food.

Question 86

What can lead to folate malabsorption?

Answer 86

```  Small bowel disease (Crohn’s, celiac)  Infection (HIV, tropical sprue)  Ileal resection  Abdominal radiation exposure  EtOH impairment of GCP II activity  Vitamin B12 deficiency  Drugs (anti-convulsants) ```

Question 87

What are the functions of Folate?

Answer 87

1. DNA/RNA Synth (thymidine (T), adenine (A), guanine (G)) 2. Methionines recycling (conversion of homocysteine to methionine) 3. s-adenosylmethionine (SAM) synth (methylation reactions)

Question 88

What happens if you are deficient in folate?

Answer 88

1. Deranged DNA synth  Uracil misincorporation (deficiency in folates means you can't convert the U's to P's. All the U's present increase the frequency at which U misincorporation occurs. The enzymes still cut the U's out, but now there are more U's being cut than normal, making the DNA more susceptible to breaking during the cutting process than normal.)  DNA strand breaks (double strand breaks fam...) 2. Hyperhomocysteinemia (folate is needed to metabolize this H-word thing. without folate, this thing increases in concentration in the blood. high amounts of this is a risk for heart disease, vascular diseasie, stroke, alzhemer;s dementia)  Elevated homocysteine in plasma  Elevated SAH levels in tissues  Decreased SAM levels in tissues

Question 89

What are the clinical manifestations of folate deficiency?

Answer 89

1. macrocytic (megaloblastic) anemia (due to inhibited DNA synth) (smear would show enlarges RBCs and macrophages with increased number of dark lobes (8)...normal amount is 3.). the cells are macrocytic because they can't divide while in the bone marrow like they normally would, as a result of the low folate. The anemia part is the fact that there are less rbcs as a result, even tho they are bigger. Note that B12 deficiency would also have macrocytic anemia. 2. hyperhomocysteinemia  Inhibited homocysteine metabolism  Increased risk of vascular disease, dementia 3. neural tube defects  Spina bifida  Anencephaly (brain exposed to amniotic fluid since skull did not close. will lead to spontaneous abortion due to failed brain formation)

Question 90

describe relationship between B12 and neural tube defects

Answer 90

increase B12 = decrease in neural tube defects. does not matter if the person was given fortified folate or supplement. if the country's diet was already B12-Lit, then the effects seen were not as great (because they were ahead of the curve to begin with). Best effects were seen in countries which were sleepin, not realizing to put B12 in their foods and then finally seeing the light that is B12.

Question 91

link relationship between folate, homocysteine, and heart disease.

Answer 91

low folate = high homocysteine = increased heart disease risk. note that if you lower homocysteine, you do not see a particular decrease in heart disease :/ weak hypothesis. but there may still be a solid correlation according to china study, which showed increased protection against stroke when homocysteine was lowered.

Question 92

How does Folate manifest in terms of toxicity?

Answer 92

Folic acid:  May mask B12 deficiency  May promote cancer growth (blocking DNA synth (due to low amounts of folate) kills cancer cells, so if you give a ton of folate, the cancer cells may just grow out of control  No real toxicity known for natural forms of folate in foods