Exam 4

Question 1

what is folate

Answer 1

reduced form of vitamin B; natural form; polyglutamates tail; less stable than folic acid

Question 2

what is folic acid

Answer 2

oxidized form of viatmin B; synthetic form; only found in fortified foods; exists as a mono glutamate; more stable than folate

Question 3

1DFE =

Answer 3

I ug food folate = .6 ug food folic acid = .5 ug folic acid on an empty stomach

Question 4

DFE =

Answer 4

ug food folate + (ug folic acid x 1.7)

Question 5

explain 1.7 and DFE

Answer 5

1.7 came from research suggesting folic acid from food was 85% bioavailable compared to 50% for folate (85%/50%=1.7), however it’s likely that this will change based on the newer evidence suggesting folate’s bioavailability from food is higher (80% of folic acid) than previously believed (100%/80%=1.25).

Question 6

cofactor form of folate

Answer 6

THF - tetrahydrofolate

Question 7

why are US foods fortified with folic acid

Answer 7

For childbearing women to lessen dangers of giving birth to a child with neural tube defects (spina bifida) due to folic acid deficiency.
The neural tube closes 21-28 days after conception and it is estimated that around 50% of pregnancies are unplanned, therefore unaware of the need for folic acid. Lower socioeconomic status women of childbearing age are also the most likely to not buy and consume supplements and they might be the ones most at risk if their food insecure.

Question 8

megaloblastic anemia

Answer 8

large, nucleated, immature red blood cells.

Question 9

megaloblastic anemia is associated with what deficiency

Answer 9

Folate is needed for DNA synthesis, so without enough of it, RBCs are not able to divide properly. As a result, fewer and poorer functioning red blood cells are produced that cannot carry oxygen as efficiently as normal red blood cells.

Question 10

scientific name of vitamin B12

Answer 10

cobalamin

Question 11

what deficiency is common among vegans and why?

Answer 11

vitamin B12. s produced by microorganisms within animal that the animal products come from, and vegans don’t eat these types of products.

Question 12

most reliable sources of B12 and why?

Answer 12

Animals consume the microorganisms in soil or bacteria in ruminant animals that produce vitamin B12.

Question 13

pernicious anemia

Answer 13

is a condition of inadequate intrinsic factor production which causes poor vit B12 absorption. Intrinsic factor is released from parietal cells in the stomach that binds to B12 in the duodenum and helps absorption into enterocytes of the ileum

Question 14

atrophic gastritis

Answer 14

occurs in people 50+ and is a chronic inflammatory condition that leads to loss of glands in the stomach, which in turn leads to decreased intrinsic factor production that causes pernicious anemia and ultimately Vit B12 deficiency.

Question 15

B12 deficiency and pernicious anemia and atrophic gastritis

Answer 15

B12 intake might be adequate during these conditions but there still may be B12 deficiency.
-often times B12 levels are normal, but because of the lack of intrinsic factor - pernicious anemia results

Question 16

folate/folic acid can mask what vitamin defiicency and how?

Answer 16

Both vitamins lead to the same megaloblastic anemia, so if given (high levels of) folate/folic acid this anemia is cured, but it does not correct the more serious neurological problems that can result from B12 deficiency. Folate/folic acid cures the symptom, but does not rectify the deficiency (just “masks” it), which makes this particularly harder to diagnose.

Question 17

intake of folate (vitamin B12) can decrease what levels?

Answer 17

homocysteine levels

Folate, vit B12 help convert homocysteine to methionine by providing methyls, thereby decreasing homocysteine levels. (But hasn’t been shown to improve CV disease outcomes)

Question 18

what is homocysteine

Answer 18

nonproteinogenic (not used for making proteins) amino

acid - found at elevated levels in people with CV disease.

Question 19

why is vitamin D conditionally essential

Answer 19

Vitamin D is unique among the vitamins in that it is part vitamin, part hormone. It is considered part hormone for two reasons: (1) we have the ability to synthesize it, and (2) it has hormone-like functions. The amount synthesized, however, is often not enough to meet our needs. Thus, we need to consume this vitamin under certain circumstances, meaning that vitamin D is a conditionally essential micronutrient.

Question 20

Understand how vitamin D3 is synthesized, activated and transported including the circulating form and the active form of the vitamin

Answer 20

synthesize vitamin D3 from cholesterol. In the skin, cholesterol converted to 7-dehydrocholesterol which in the presence of UV-B light turns into vitamin D3. Synthesized vitamin D will combine with vitamin D- binding protein (DBP) to be transported to the liver. Dietary vitamin D3 is transported to the liver via chylomicrons and taken up into chylomicron remnants. Once in the liver 25-OHase adds a hydroxyl group at the 25th Carbon forming 25(OH)D or Calcidiol, this is the circulating form of vitamin D. The active form of Vit D3 is formed by the addition of another hydroxyl group by enzyme 1 alpha-OHase, thus forming 1,25(OH)2D or calcitriol in the kidney.

Question 21

Difference between D2 and D3

Answer 21

The form produced by plants and yeast is vitamin D2 (ergocalciferol), and the form made by animals is vitamin D3 (cholecalciferol).
D3 is “87% more potent in raising and maintaining serum 25(OH)D concentration and produces a 2 to 3 fold greater storage of vitamin D” than D2.

Question 22

what environmental factors affect vitamin D synthesis

Answer 22

Latitude-the further from the equator, less UV light exposure leading to less vitamin D3 synthesis.
Seasons- the angle of the sun relative to how many UV-B photons absorbed before reaching the earth’s surface.
Time of day- rises in the morning, peaks at noon, then declines the rest of the day.
Skin pigmentation- darker skin requires 5-10 times greater exposure for the same amount of vitamin D3 synthesis as lighter colored skin.
Age- results in a decrease in 7-dehydrocholesterol resulting in a 75% reduction in vitamin D3 by age 70.
Clothing- less clothes leads to more viatmin D3 synthesis and vice versa

Question 23

debate sensible sun exposure

Answer 23

Researchers recommend sun exposure on the face, arms, and hands for 10-15 minutes 2-3 times per week between 10AM-3PM. However, dermatologists do not like “sensible sun exposure” because this is also the peak time for harmful sun exposure. Dermatologists say that “sensible sun exposure” appeals to those who are looking for a reasons to support tanning and are at highest risk (primarily young, fair-skinned females) of sun damage. They argue that vitamin D can be provided through supplementation.

Question 24

Milk fortification with vitamin D and ethnicities

Answer 24

They are often time lactose intolerant. This means that they do not have enough lactase to break down the lactose. This leads to lactose being fermented in the colon and causing unpleasant symptoms.
darker skin people already require more sun exposure to increase vitamin D3 in their bodies, and if they are also lactose intolerant they cannot rely on fortified dairy products for vitamin D either

Question 25

Have an integrated understanding of how the body responds to low blood calcium levels, including PTH and 1,25(OH)2 D, vitamin D receptor and calbindin

Answer 25

Low Blood Ca levels PTH and 1,25(OH)2D-The parathyroid senses low blood calcium concentrations and releases PTH, which has 3 effects.
1. Increased bone resorption- Hydroxyapatite is broken down to release Ca and phosphate.
2. Decreased Ca, increased phosphorus excretion
3. Increased 1,25(OH)2D activation in kidney by raising 1alpha-OHase levels. 1,25(OH)2D then increases Ca absorption to help raise blood Ca levels.
Vitamin D receptor and calbindin- 1,25(OH)2D moves from the kidney or the tissue itself into the nucleus where it binds to the vitamin D receptor (VDR),increasing transcription of mRNA. The mRNA then moves into the cytoplasm to synthesize specific proteins. It’s through this action that 1,25(OH)2D is able to increase calcium absorption. The target gene is the calcium-binding protein calbindin. Thus, increased 1,25(OH)2D leads to increased calbindin mRNA that increases calbindin protein levels.

Question 26

if blood Ca2+ levles get too high what hormone is released and from where

Answer 26

calcitonin is released by the thyroid gland

Question 27

calbindin’s function

Answer 27

Calcium binding protein that facilitates uptake through TRPV6 and transport across the enterocyte.

Question 28

Know the inhibitors of calcium absorption and why calcium content of a food alone can be misleading

Answer 28

-Phytates: whole grains, legumes
-Oxalate: spinach, rhubarb, sweet potatoes, dried beans
It is important to know that just because one food source has a high amount of calcium in it, if it is not bioavailable then it cannot be absorbed and is therefore not a good source of calcium. Example: a serving of rhubarb may contain a higher amount of calcium than milk. However, milk would be a better source of calcium because it is more bioavailable because rhubarb contains oxalate (a calcium absorption inhibitor).

Question 29

Understand the differences between osteomalacia, osteopenia, and osteoporosis and normal bone

Answer 29

-Osteomalacia: bone mass is normal, but the matrix to mineral ratio is increased
meaning there is less mineral in bone
-Osteopenia: bone mass is decreased, but the matrix ratio is not altered from normal bone. The condition is intermediate in between normal and osteoporosis.
-Osteoporosis: Bone mass is further decreased from osteopenia, but the matrix to mineral ratio is not altered from normal bone.

Question 30

Understand what peak bone mass and bone mineral density are and why it is important to build peak bone mass

Answer 30

Peak bone mass is the maximum amount of bone that a person will build in his/her lifetime. It is reached somewhere around 30 years of age. It is important to build, because after the peak bone mass declines. The higher peak bone mass an individual has the lower his/her risk of developing osteoporosis.

Question 31

Know why females are at higher risk of osteoporosis than males

Answer 31

For women after menopause, bone mass decreases dramatically because of the decrease in estrogen production. Also women have lower bone mass than men to begin with.

Question 32

why is the bioavilability of phytate low? what impact does it have on other minerals?

Answer 32

The bioavailability of phosphorus from phytate is poor because we lack the enzyme phytase. It inhibits the absorption of Calcium, Iron, Zinc, and phosphorus.

Question 33

Know why fluoride exposure or consumption leads to decreased cavity formation

Answer 33

-Fluoride alters the mineralization of bones and teeth. It does this by replacing hydroxyl (OH) ions in hydroxyapatite forming fluorohydroxyapatite. Fluorohydroxyapatite is more resistant to acid degeneration than hydroxyapatite - leading to fewer cavities.

Question 34

Understand what happens in fluorosis

Answer 34

-This is a result of chronic toxicity of fluoride. It is characterized by mottling and pitting of teeth.

Question 35

Understand where we get most ingested fluoride from and the public health implications of this

Answer 35

-Fluoridated water. This is a debatable issue. However, the prevalence of fluorosis has decreased with this act.

Question 36

Know the different forms of vitamin K, their origins, and differences in their structures

Answer 36

phylloquinone (K1), the plant form of vitamin K, 3 outside of the brackets indicates the structural unit inside the brackets is repeated 3 times.
menaquinone (K2), is synthesized by bacteria in the colon, have side chains of varying length.
menadione, the synthetic form, a tail, similar to the one found in menaquinone, has to be added to menadione for it to be biologically active.

Question 37

Have an integrated understanding of what Gla proteins are, why vitamin K is needed for their production, what enzyme forms Gla, and how they are important in blood clotting

Answer 37

The enzyme, gamma-glutamyl carboxylase, using a vitamin K cofactor, converts glutamic acid to gamma-carboxyglutamic acid (Gla).

Gla proteins contain glutamic acid(s) that have been converted to gamma-carboxyglutamic acid(s).

Blood clotting occurs through a cascade of events, there are a number of Gla proteins in this cascade. If the proteins within the blood clotting cascade are not activated to Gla, the cascade does not proceed as normal leading to impaired blood clotting.

Question 38

why do babies receive vitamin K injections

Answer 38

Because there is poor transfer of vitamin K across the placental barrier, their gastrointestinal tracts do not contain vitamin K producing bacteria, and breast milk is generally low in vitamin K.

Question 39

Understand how warfarin and dicumarol act as anticoagulants

Answer 39

Inhibits the regeneration of vitamin K. This reduces the amount of Gla in the blood clotting proteins thus reducing the clotting response. Regenerated so it can serve as a cofactor again to increase the amount of Gla in the blood to increase the clotting response.

Question 40

dietary sources of vitamin A

Answer 40

Know the dietary sources of vitamin A and where they come from
Retinyl/retinol esters (Animal Products)
Provitamin A Carotenoids (Plants)

Question 41

Understand the difference between provitamin A carotenoids, nonprovitamin A carotenoids, and preformed vitamin A

Answer 41

Provitamin A carotenoids are those that can be cleaved to form retinal, while the non-provitamin A carotenoids cannot.
Preformed vitamin A means that the compound is a retinoid. Preformed vitamin A is only found in animal products.

Question 42

Understand what RAEs are and why they are needed

Answer 42

They take into account the bioavailability and bioconversion of the provitamin A carotenoids, as some are more bioavailable than others.

Question 43

Understand why the RAEs are different for beta-carotene versus other provitamin A carotenoids

Answer 43

-After provitamin A carotenoids are taken up into the enterocyte, some are cleaved to form retinal
- symmetrical beta-carotene, it is cleaved in the center to form 2 retinal molecules
Alpha-carotene and beta-cryptoxanthin are asymmetrical, thus they can be used to form only 1 retinal.

RAE’s are different because they form different amounts of retinal after uptake from the enterocyte

Question 44

Know how provitamin A carotenoids and vitamin A are absorbed, transported and stored in the body

Answer 44

Once provitamin A carotenoids are taken up into the enterocytes, they are: (1) cleaved to retinal and then converted to retinol or (2) absorbed intact and incorporated into chylomicrons.
Retinol in the enterocyte is esterified, forming retinyl esters. The retinyl esters are packaged into chylomicrons (CM) and enter the lymph system. Once the chylomicrons reach circulation, triglycerides are cleaved off to form chylomicron remnants (CM Rem). These are taken up by hepatocytes, where the retinyl esters are de-esterified to form retinol.
The liver is the major storage site of vitamin A. For storage, the retinol will be transported from the hepatocytes to the stellate cells and converted back to retinyl esters, the storage form of vitamin A. If vitamin A is needed to be released into circulation, retinol will combine with retinol

binding protein (RBP). Retinol + RBP are then bound to a large transport protein, transthyretin (TTR). It is believed that retinol + RBP would be filtered out by the kidney and excreted in urine if it was not bound to TTR1.

Question 45

Know why vitamin A is important for night vision, and why this is the 1st symptom of deficiency

Answer 45

Cones are responsible for color vision, while rods are important for seeing black and white. Within the rods, 11-cis retinal combines with the protein, opsin, to form rhodopsin. When light strikes rhodopsin, the compound splits into opsin and all-trans retinal. This sends a signal to your brain for us to “see” .
Most all-trans retinal is converted back to 11-cis retinal through a series of steps so it can continue to be used to form rhodopsin. However, this recycling is not 100% efficient. Vitamin A stores, or continued intake, is required to provide the 11-cis retinal needed to continue to form rhodopsin.

Question 46

Understand how the retinoic acid receptor works and why all-trans retinoic acid is the active form of vitamin A

Answer 46

All-trans retinol is converted to all-trans-retinal, and then to all-trans-retinoic acid. RAR and RXR are paired, or dimerized, on the retinoic acid response element (RARE) in the promoter region of target genes. The binding of all-trans retinoic acid causes the transcription and ultimately the translation of target proteins.
All-trans retinoic acid it is the ligand for RARs, leading to many of the biologic effects attributed to vitamin A.

Question 47

Understand why vitamin A deficiency is a problem in some countries, what golden rice and orange corn contain, and how they can possibly decrease vitamin A deficiency

Answer 47

In many developing countries, they do not have a stable dietary source of retinoids or provitamin A carotenoids. One way to counter vitamin A deficiency in developing countries is to for staple crops, like rice and corn, to contain beta-carotene. Golden Rice was genetically modified to produce beta-carotene. Corn kernels acquired chemicals called carotenoids, and became yellow.
One of these carotenoids is beta carotene, which gives us vitamin A. So, yellow corn is a little bit more nutritious than white corn.

Question 48

Know why it is important for pregnant women not to consume too high levels of vitamin A or Accutane

Answer 48

Toxic levels of vitamin A are also teratogenic, which means they could cause birth defects.

Question 49

Know what happens when you consume high amounts of beta-carotene versus vitamin A itself

Answer 49

A nontoxic condition known as carotenodermia occurs when large amounts of beta-carotene are consumed, where the accumulation of the carotenoid in the fat below the skin causes the skin to look orange.

Question 50

Know the different forms of iron

Answer 50

heme iron and non-heme iron

It is estimated that 25% of heme iron and 17% of non-heme iron are absorbed

Question 51

Know the 2 forms of non-heme iron and the difference between the absorption of the

Answer 51

Ferric (Fe3+, oxidized)

Ferrous (Fe2+, reduced) (absorbed better)

Question 52

Have an integrated understanding of iron absorption, transport, and storage

Answer 52

non-heme transporter - DMT1 : iron into enterocyte
heme transporter: 1HCP-1 takes up heme and is metabolized to Fe2+
-Fe2+: used by enzymes or proteins or stored in enterocyte bound to ferritin,
-Fe2+: transported through ferroportin into circulation
FE3+ is transported by transferrin which binds to a transferrin receptor to take the iron into the cell tissue

Question 53

Know some enhancers and inhibitors of non-heme iron absorption

Answer 53

• Vitamin C - required by reductase enzyme to reduce Fe3+ to Fe2+
  
  • Unidentified meat protein factor (MPF)
  • these are enhancers
  • Phyate, Oxalate, and Calcium bind/chelate to iron and prevent its absorption
  • these are inhibitors

Question 54

Know how we regulate Fe status and decrease absorption if levels get too high

Answer 54

The liver has an iron sensor so when iron levels get high, this sensor signals for the release of hepcidin (hormone). Hepcidin causes degradation of ferroportin (where does this occur? - in the enterocyte). Thus, the iron is not allowed to be transported into circulation because ferroportin transports Iron2+ into circulation.

Question 55

Understand the functions of Fe in the body

Answer 55

3 primary functional iron subcompartments.
Hemoglobin contains heme that is responsible for red blood cells’ red color. Hemoglobin carries oxygen to tissues.
Myoglobin is similar to hemoglobin in that it can bind oxygen. However, instead of being found in blood, it is found in muscle.
Iron containing enzymes; Iron is a cofactor for the antioxidant enzyme catalase that converts hydrogen peroxide to water. Iron is also a cofactor for proline and lysyl hydroxylases that are important in collagen cross-linking.

Question 56

Understand what hematocrit is and the limitations of this assessment and hemoglobin measurement for iron status

Answer 56

Hematocrit is a measure of the proportion of red blood cells as compared to all other components of blood. This measure is among the last to indicate that iron status is depressed because circulating iron levels are not altered until you reach iron deficiency.

Question 57

Understand what occurs in iron deficiency and people who are especially at risk or require more Fe

Answer 57

-Microcytic (small cell) anemia
-Women of childbearing age because of menstruation
-Pregnant women because of increased blood volume
-Infants and children because they do not have iron stores and they go through fast
growth/development
-Vegans are also at risk because they do not consume enough heme iron -mainly found
in animal products
-Extreme runners may also be at risk because of “foot strike hemolysis” -breakdown of red blood cells from impact.