Exam 3 Material - HN

why it is important to have adequate levels of pantothenic acid

1. Pantothenic acid is a part of coenzyme A (CoA), which is used in fatty acid oxidation. 2. It is part of acyl carrier protein, which is important in fatty acid synthesis.

The two forms of alpha-tocopherol are designated

1. Natural New designation: RRR-alpha-tocopherol (because all 3 positions are RRR) 2. Synthetic New designation: all-rac-alpha-tocopherol (because it is a racemic mixture) Keep in mind the natural and synthetic are describing the stereochemistry of alpha-tocopherol and not whether it is naturally derived.

Meaningful Antioxidant

A meaningful antioxidant has two characteristics (these are based on the assumption that the compound is an antioxidant): 1. Found in appreciable amounts right location where there are free radicals/ROS that need to be quenched 2. It is not redundant with another antioxidant that is already serving as an antioxidant

cretinism

A more serious consequence of iodine deficiency occurs during pregnancy to the fetus. Iodine deficiency during this time can lead to the mental and physical retardation known as cretinism. This condition is characterized by severe hypothyroidism, stunted growth, speech loss, and paralysis.

You've told your friend a little about what you've learned about natural versus synthetic alpha-tocopherol. But when you show him/her the different options that can be formed when alpha-tocopherol is synthesized, he/she doesn't understand why RSR results in higher blood alpha-tocopherol levels than SRS if 2R alpha-tocopherol is the form that results in higher blood levels. What would you tell your friend?

Alpha-TTP binds better when R is in the second position. The first letter signifies what is in the second position, therefore RSR would have an R in the second position.

Antioxidant Network

Antioxidants are thought to work in concert with one another, forming what is known as the antioxidant network.Alpha-tocopherol is believed to be the first part of an antioxidant network where it is oxidized to donate an electron to stabilize reactive oxygen species.Alpha-tocopherol (major form of vitamin E in our body) is oxidized, forming an alpha-tocopherol radical. This donation of an electron stabilizes reactive oxygen species. Alpha-tocopherol radical can then be reduced by the donation of an electron from ascorbate (vitamin C),Ascorbate is oxidized forming dehydroascorbate to regenerate (reduce) alpha-tocopherol. Ascorbate is then regenerated by the selenoenzyme thioredoxin reductase. This demonstrates how antioxidants can function as a network to regenerate one another so they can continue to function as antioxidants.

Scientific name of Vitamin C

Ascorbate Ascorbic acid

differences between biotin and biocytin and what role biotinidase has

Biocytin is acted on by the enzyme biotinidase and forms free biotin and lysine. Biocytin is biotin plus the amino acid lysine. So what is biocytin?

Water soluble vitamins

C,B

why should you care about collagen

Collagen is estimated to account for 30% or more of total body proteins. Collagen contains a number of hydroxylated prolines and lysines that are needed for collagen strands to properly cross-link. This cross-linking is important for collagen to wind together like a rope, forming the strong triple helix known as tropocollagen. But if there isn't enough ascorbic acid available, the collagen strands are underhydroxylated and instead of forming strong tropocollagen, the underhydroxylated collagen is degraded. This weak collagen then results in the symptoms seen in the vitamin C deficiency, scurvy Collagen contains a number of hydroxylated prolines and lysines that are needed for collagen strands to properly cross-link Prolyl and lysyl hydroxylases need Fe 2+ to function Ascorbic acid reduces Fe3+ to Fe 2+ Under Hydroxylated collagen is degraded

Fat soluble vitamins

D,E,K,A

Know the components of the DRIs

DRIs are a collective term to refer to these components: Estimated Average Requirement (EAR) Recommended Dietary Allowance (RDA) Adequate Intake (AI) Tolerable Upper Intake Level (UL)

difference between nicotinic acid and nicotinamide related to toxicity and improvements in blood lipid profiles and how these effects are mediated including the role of the nicotinic acid receptor

Dietary niacin toxicity is rare. However, nicotinic acid (not nicotinamide) can improve people's lipid profiles when consumed at levels far above the RDA. For instance the RDA & upper limit (UL) is 14 or 16 (women & men) and 35 mg (both), respectively. Many people are taking 1-2 grams (up to 6 g/day) to get the benefits in their plasma lipid profiles.

Alpha-tocopherol transfer protein, which is found in the small intestine, helps facilitate the incorporation of alpha-tocopherol into chylomicrons. (T/F)

False; ATTP, which is found in the liver, helps facilitate the incorporation of alpha-tocopherol in to VLDL.

Consuming too much ascorbic acid can result in blood clotting problems by inhibiting the action of vitamin K. (T/F)

False; Consuming too much Vitamin E (alpha-tocopherol) can result in blood clotting problems by inhibiting the action of vitamin K.

High dose riboflavin supplementation is a first line recommendation for women experiencing morning sickness. (T/F)

False; High does vitamin B6 supplementation is a first line recommendation for women experiencing morning sickness.

cofactors formed from riboflavin

Flavin adenine dinucleotide (FAD) & flavin mononucleotide (FMN).

How AI's are set

For nutrients lacking the research evidence needed to set an EAR, an AI is set instead.An AI is a level that appears to be adequate in a defined population or subgroup.

Why too much Vitamin E may cause blood clotting problems

High levels of vitamin E intake do not result in a noted toxicity. However, higher levels of intake are associated with decreased blood coagulation.It is believed that this increased bleeding risk is due to a vitamin E metabolite that has anti-vitamin K activity.

Why are humans different compared to other mammals in regards to Vitamin C?

Humans are one of the few mammals that don't synthesize vitamin C, making it an essential micronutrient.

what form of vitamin E the DRI committee chose to use for setting RDAs and what impact this has on food items like soybean oil

In 2001, the Dietary Reference Intake (DRI) committee decided only 2R forms of alpha-tocopherol should be used to estimate the requirement, because these forms bind to alpha-TTP.

ascorbate recycling

In ascorbic acid recycling, ascorbic acid is oxidized to dehydroascorbic acid (DHA). DHA is then transported into the cell moving with its concentration gradient using a GLUT transporter. Once inside the cell, DHA is reduced back to ascorbic acid, thus maintaining the DHA gradient. As a result, the cell is able to accumulate high levels of ascorbic acid

Difference between natural and synthetic alpha-tocopherol

In natural alpha-tocopherol, all 3 chiral centers are in the R configuration. Thus, it is designated RRR-alpha-tocopherol. Synthetic alpha-tocopherol is a racemic (equal) mixture of all the different stereochemical possibilities at the three chiral centers. These are: RRR RRS RSS RSR SRR SSR SSS SRS.

what type of anemia is formed in vitamin B6 deficiency and why it develops

Microcytic hypochromic anemia is formed in vitamin B6 deficiency and why it develops is because there is a decrease in the synthesis of heme-. There is decrease in heme synthesis because the cells are small and have low color. Why is there a decrease in heme synthesis?

how ascorbate recycling allows tissues to concentrate high levels of vitamin C

Most water-soluble vitamins are not stored in the body. Vitamin C is not stored, but is accumulated in certain tissues in the body where it can be 5-100 times higher than found in the plasma​.

the symptoms of "niacin flush" and why long acting supplements are used in some circumstances

Niacin flush causes the dilation of capillaries which is accompanied by tingling and can be painful. A nicotinic acid receptor has been used to mediate the flush, but in doesn't benefit lipid profiles. So nicotinic acid supplementation can improve the lipid profile, but also lead to flush. Nicotinamide supplementation does not result in either.

cofactors formed from niacin

Niacin is important for the production of two cofactors: nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP+​ ​)

What micronutrient has an equivalent set by the DRI committee because it can be synthesized from something else? Make sure you include what the micronutrient is synthesized from in your answer.

Niacin, it can be synthesized from tryptophan

Have an integrated understanding of how research on Keshan disease has led to findings that might explain how someone else can serve as a host for a virus that then could make you sick

One group of mice was fed an adequate selenium diet and another group a deficient selenium diet. They were then infected with coxsackievirus that was mostly avirulent, that doesn't cause a disease, but also contained some virulent viruses that causes a disease. They found that the selenium deficient animals developed severe heart pathology, while the selenium adequate animals did not develop heart pathology. They then isolated the virus from the hearts of the mice from both groups and found that the coxsackievirus from the deficient animals hearts had become mostly virulent​. They took the isolated virus from the selenium-deficient mouse hearts and infected selenium adequate animals with it. The selenium adequate animals developed the severe heart pathology like the selenium-deficient animals had previously. Research found mutations in the virus from the selenium-deficient animals that they believe caused it to become virulent. They believe that high oxidative stress in these animals leads to mutations in the virus, causing it to become virulent. Research has found similar results with vitamin E. Researchers are also examining the effects on other viruses such as influenza (flu) and HIV.

the major cofactor formed from vitamin B6

PLP (pyridoxal phosphate)

why populations that consume only corn can develop pellagra and through what process this can be prevented

Pellagra is a niacin deficiency. This is no longer a common deficiency in developed countries, but was in the U.S. in the early 1900s. This was because corn was a staple crop, meaning it was what people primarily consumed. The bioavailability of niacin from corn is poor unless treated with a base to release the bound niacin.

Know the different forms of vitamin B6

Pyridoxine, pyridoxal, and pyridoxamine

The plasma alpha-tocopherol levels after receiving RRR-alpha-tocopherol vs. all-rac-alpha-tocopherol.

RRR-alpha-tocopherol is 2x higher than all-rac-alpha-tocopherol.This is not a surprise because approximately 50% of all-rac-alpha-tocopherol is 2R alpha-tocopherol that binds well with alpha-TTP

Why are there so many B vitamins and why are the numbers not in sequential order?

Researchers realized that factor B actually consisted of two factors that they termed B​1​ and B​2.​ Then they realized that there are multiple components in B​2,​ and they began identifying the wide array of B vitamins that we know today. Vitamins B​4,​ B​8,​ B​10,​ and B​11​ were discovered and then removed leaving us with the B vitamins

why milk is not stored in glass bottles anymore

Riboflavin is photosensitive, meaning that it can be destroyed by light. This was a problem in the old days when the milkman delivered milk in clear glass bottles. These have now been replaced by cartons or opaque plastic containers to help protect the riboflavin content of the milk.

Know what a selenoprotein is and how selenoenzymes differ from other enzymes for which minerals are cofactors

Selenium's antioxidant function is not due to the mineral itself, but a result of selenoproteins. Selenoproteins, containing the amino acid selenocysteine. In most enzymes, the mineral is a cofactor that is external to the enzyme, Selenoenzymes contain selenocysteine as an amino acid in the active site of the enzyme. Thus, in selenoenzymes, selenium does not serve as a cofactor, which is different than most minerals required for enzyme function.

Understand why selenocysteine is/could be considered the 21st amino acid

Selenocysteine is considered the 21st amino acid by some, because there is a codon that directs its insertion into selenoproteins.

cofactor formed from thiamin

TTP

How RDA's are set

The RDA is the measure that professionals use to assess the quality of people's diets. It is the requirement estimated to meet the needs of 97.5% of the population. But the RDA is calculated using the EAR.

what public health policy has led to decreases in iodine deficiency disorders and may be a cheap way to raise the world's IQ

The World Health Organization calls iodine deficiency "the world's most prevalent, yet easily preventable, cause of brain damage​." By saying it is easily preventable, they are referring to the ability of salt iodization to prevent brain development problems.

Linus Pauling & what he advocated for vitamin C

The person who popularized taking megadoses of vitamin C was Dr. Linus Pauling. Dr. Pauling was a chemist, and is the only person to receive 2 unshared Nobel Prizes.Later in his life Pauling became convinced that megadoses of vitamin C could prevent the common cold. Later he came to believe that vitamin C could prevent cardiovascular disease, cancer, and combat aging. The RDA is only 75-90 mg/day for adults and Pauling recommended taking 1-2 grams of vitamin C daily​. These mega doses of vitamin C Pauling recommended were seen as creating 'expensive urine.' This was thought by people because vitamin C is water-soluble so the excess amount consumed by the supplement would just be excreted in the urine. Expensive urine?

why consuming large amounts of raw egg whites can result in biotin deficiency

The potential problem with consuming raw eggs routinely is that raw egg whites contain a protein called avidin which binds biotin and prevents its absorption. However, it would take more than two dozen egg whites consumed daily over many months to cause a deficiency, making this an unlikely occurrence. Cooking denatures avidin and prevents it from binding biotin, meaning that cooked eggs are not a concern.

structural differences between tocopherols and tocotrienols

The structural difference between tocopherols and tocotrienols is that the former have a saturated tail, while the latter have an unsaturated tail. What about difference among tocopherols (alpha, beta etc.) and tocotrienols?

why iodine is important for thyroid hormones and why thyroid hormone levels are important

The thyroid accumulates most absorbed iodine, keeping it for use to synthesize thyroid hormone. Thyroid hormone regulates the basal metabolic rate and is important for growth and development. Why is it important for thyroid hormone specifically? iodine. Iodine's only, yet critical, function is that it is required for thyroid hormone synthesis

difference between wet and dry beriberi

There are two major forms of beriberi: dry and wet. Dry beriberi affects the nervous system, with symptoms such as loss of muscle function, numbness, and/or tingling. Wet beriberi affects the cardiovascular system resulting in pitting edema, along with enlargement of the heart.

Difference between macrominerals, trace minerals (microminerals), and ultratrace minerals

There is not an exact, agreed on definition for how the different categories are defined, but in general they are defined by the amount required and found in the body such that: Macrominerals > Trace Minerals > Ultratrace Minerals

How EAR's are set

Therefore, the EAR needs to be set before an RDA can be set. There must be applicable research in order to set an EAR. An EAR is the estimated requirement for 50% of the population.Notice that for the EAR, the risk for inadequacy is 0.5 (50%) whereas the RDA the risk of inadequacy is 0.025 (2.5%).

Your friend is a chemist who has an interest in synthesizing alpha-tocopherol. He/she has figured out a way to control the R stereochemistry at 2 of the chiral centers, and can produce the following isomers individually. He/she only has the time to produce 2 of them though. Which would you recommend he/she focus on and why? (SRR, RSS, SSR, RRS)

They should focus on the RSS and RRS because they bind better to the alpha-TTP.

why consumption of a white rice staple diet results in beriberi and what this is a deficiency of

Thiamin deficiency is rare in developed countries, but still occurs in poorer countries where white (aka polished) rice is a staple food. During the polishing process, thiamin, and many other nutrients, are removed. Thiamin deficiency is known as beriberi.

What form of Vitamin E we consume as Americans the most and what form circulates at the highest levels

Three-fourths of the oil Americans consume is soybean oil. As a result, it is estimated that we consume 2-4 times more gamma-tocopherol than alpha-tocopherol. Alpha-tocopherol is found in higher levels in circulation because of its ability to bind to alpha-TTP.

purpose of niacin equivalents

To account for niacin synthesis from tryptophan, niacin equivalents (NE) were created by the DRI committee to account for the amount of niacin in foods as well as their tryptophan content.

How UL's are set

Tolerable Upper Intake Level (UL). This is the highest level of daily nutrient intake that is unlikely to pose risk of adverse health effects to almost all individuals in the population. To set this, the committee first sets a no observed adverse effect level (NOAEL) and/or the lowest observed adverse effect level (LOAEL).The UL is then set lower based on a number of uncertainty/safety factors off the NOAEL or LOAEL.Notice the NOAEL at the point where no adverse effects have been reported. The LOAEL is somewhere above the NOAEL. The UL is set at a level where it is believed that people will not experience the selected adverse effect.

SSS alpha-tocopherol supplementation will result in an equivalent blood alpha-tocopherol concentration compared to equivalent supplementation of SRR alpha-tocopherol. (T/F)

True; neither one would bind well to ATTP

why it might be problematic to take large amounts of vitamin B6 for carpal tunnel syndrome, morning sickness, or PMS

Vitamin B6 is unlike many other vitamins in that it can produce toxicity. People with these conditions take it as supplements in higher amounts and if toxicity occurs it can lead to neurological damage.

Friend discovered fat soluble compound that reduces Fe3+ to Fe2+ more effectively in vivo than ascorbic acid. It is also found at higher concentrations in tissues than ascorbic acid, despite only needing to be consumed once a year. They think the compound will prevent scurvy in populations with little Vitamin C intake. Do you think it'll be effective? Why or why not?

Yes, since the new compound in found in higher levels it is more meaningful. It is making vitamin C redundant so we wouldn't need to consume it.

How antioxidant vitamins and minerals quench free radicals

You have probably heard the saying "take one for the team." Instead of taking one for the team, antioxidants "give one for the team." The 'giving' is the donation of an electron from the antioxidant to a free radical, in order to regenerate a stable compound.Donating an electron is how vitamins act as antioxidants. Minerals, on the other hand, are not antioxidants themselves. Instead, they are cofactors for antioxidant enzymes.

Free Radical

a molecule with an unpaired electron in its outer orbital.Free radicals are highly reactive because they actively seek an electron to stabilize the molecule Normal oxygen is converted to an oxygen free radical by losing one electron in its outer orbital, leaving one unpaired electron

selenoenzyme

a selenoprotein that has enzymatic function.

Reactive Oxygen Species

an oxygen-containing, free radical species

Another friend decides to eat white rice exclusively for the rest of their life that the boils in water to prepare. Would this put them at risk of developing a specific deficiency? If so name the deficiency and the micronutrient that he/she is at risk of being deficient in.

beriberi, thiamin

selenoprotein

contain selenocysteine as an amino acid

Why is the ORAC not a meaningful indicator of antioxidant action?

going back to the two characteristics of meaningful antioxidants, there really is no evidence that shows that a high ORAC score leads to any benefit ​in vivo.This is because the measure also doesn't take into account characteristics such as bioavailability.Many of these purported super antioxidants have not been shown to be absorbed or maintained in the body in a way that would suggest that they would be meaningful antioxidants

2 Iodine Deficiency Disorders

goiter and cretinism

why vitamin C may increase risk of kidney stones

high intake of vitamin C increases excretion of uric acid (urate) and oxalic acid (oxalate).These compounds are the primary components of 2 types of kidney stones.

What are IU's

international units (IU). IUs are a unit that are used to describe the bioactivity of different compounds, including 4 vitamins: A, D, E, and C.Most supplements use IUs. IUs are not as common on food items.For vitamin E, IUs are specific for alpha-tocopherol and adjusted for the molecular weight of the different forms (alpha-tocopherol acetate etc.).

goiter

is a painless deficiency condition that results from the enlargement of the thyroid to help increase its ability to take up iodine.

Example of a meaningful antioxidant

lycopene and vitamin E (alpha-tocopherol), which are both fat-soluble antioxidants. lycopene is 10-fold more effective in quenching singlet oxygen than alpha-tocopherol1​ ​. However, when you look at the concentrations found in the body, there is far more alpha-tocopherol than lycopene.Thus, despite the fact that lycopene is a better antioxidant ​in vitro​, since the concentration of alpha-tocopherol is so much higher in tissues (locations of need), it is likely the more meaningful antioxidant.In addition, if lycopene and alpha-tocopherol have similar antioxidant functions (fat-soluble antioxidants), lycopene's potential antioxidant action is redundant to alpha-tocopherol's antioxidant function and thus, also less likely to be a meaningful antioxidant

Your friend decides to eat corn on the cob exclusively for the rest of his/her life that he/she places in wax paper and microwaves to prepare. Would this put him/her at risk of developing a deficiency of specific micronutrient. If so name the deficiency, and the micronutrient that he/she is at risk of being deficient in.

niacin

What impact does the DRI form of vitamin E have on food items like soybean oil

other forms of vitamin E (gamma-tocopherol, tocotrienols etc.) do not count toward the requirement and the unit is now mg of alpha-tocopherol. As a result, soybean, corn, and flaxseed oils, which are good sources of gamma-tocopherol, are no longer considered to be good sources of vitamin E.

What is ORAC

oxygen radical absorbance capacity (ORAC) the USDA removed its table of ORAC values "due to mounting evidence that the values indicating antioxidant capacity have no relevance to the effects of specific bioactive compounds, including polyphenols on human health.

2 common epigenetic modifications are and what effect they have

the 2 main epigenetic modifications play a major role in determining what genes are expressed: DNA methylation Histone modification DNA methylation is the addition of a methyl group to a DNA base, which decreases gene transcription. Conversely, demethylation increases gene transcription Histone modification occurs when there are additions or subtractions to the histones themselves. The most common is acetylation (addition of an acetyl group) or deacetylation of histones. Together, these modifications to DNA and histones are known as the epigenetic code

Oxidative Stress

the imbalance between the production of ROS/free radicals and the body's ability to quench them.

how alpha-tocopherol transfer protein (alpha-TTP) determines circulating vitamin E concentrations

the primary form of vitamin E found in the body is alpha-tocopherol. The major, and possibly only, function of vitamin E is as an antioxidant. The liver contains a protein called alpha-tocopherol transfer protein (alpha-TTP), which is responsible for maintaining higher levels of alpha-tocopherol in the body. Alpha-TTP preferentially binds to 2R alpha-tocopherol and helps facilitate its incorporation into VLDL. 2R means any form of alpha-tocopherol in which the 2 position is in the R conformation.Other forms of vitamin E (gamma-tocopherol, tocotrienols) don't bind well to alpha-TTP and thus, are found in lower levels than alpha-tocopherol in the body.

difference between thyroid hormones

two primary forms of thyroid hormone are triiodothyronine (T​3)​ and thyroxine (T​4)​ . T3 has three Iodine groups while T4 has four iodine groups. How do they differ on the basis of iodine? T​4 i​s the primary circulating form, and is really a prohormone that is converted to the active T​3 form.

symptoms of scurvy and the roles of collagen, vitamin C, and iron in its development

vitamin C deficiency, known as scurvy, displays symptoms that are a result of weak collagen, that in turn, weakens connective tissue throughout the body. Symptoms of scurvy include bleeding gums, pinpoint hemorrhages, and corkscrew hairs.Additional symptoms include impaired wound and fracture healing, easy bruising, and loose or decaying teeth. Scurvy can be fatal if not treated.