Vitamins

Question 1

What are the water soluble vitamins

Answer 1

B Vitamins and Vitmain C

Question 2

What is thiamine and where is it found

Answer 2

Thiamine (B1)

Thiamine is found in grains, legumes, and meat. It is also used to fortify grains used in cereals, breads, and other baked products

Question 3

Reactions that involve thiamine

Answer 3

- Oxidative decarboxylations - These reactions function in energy metabolism, transitioning from glycolysis to TCA cycle (pyruvate dehydrogenase) and within TCA cycle (α-ketoglutarate dehydrogenase). Thiamine plays a major role in the production of acetyl-CoA, used to make acetylcholine

- Thiamine also plays a role as a carbonyl carrier in carbon assimilation reactions.

Here it functions in the non-oxidative phase of pentose phosphate pathway (transketolase) recycling intermediates that keep the pathway operating to synthesize NADPH (antioxidant, reductive biosynthesis) and pentose phosphates used in nucleotide synthesis.

Question 4

Causes of thiamine deficiencies

Answer 4

Refined rice

Alcoholism - This form of thiamine deficiency is associated with changes in GI absorption due to chronic alcoholism, liver damage may also affect conversion to thiamine pyrophosphate

Question 5

Diseases involving thiamine deficiency

Answer 5

Beriberi - cardiovascular (CHF = wet beriberi) and neuro manifestations (dry beriberi)

Wernicke-Korsakoff syndrome - Specific neurological features associated with thiamine deficiency linked to alcoholism: confusion, psychosis, memory problems, coma

Question 6

What is riboflavin, forms, and source

Answer 6

B2

The coenzyme forms of riboflavin are flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN)

Milk, meat, some vegetables

Question 7

Reactions involving riboflavin

Answer 7

Electron carrier - oxidation/reductions.

Functions in energy metabolism as part of pyruvate and α-ketoglutarate dehydrogenases and as an electron carrier in the TCA cycle and electron transport chain.

Also functions in fat catabolism.

Question 8

Causes of riboflavin deficiencies

Answer 8

Flavin deficiencies are often found in association with deficiencies of other B vitamins in North America (chronic alcoholism), but can be found on its own in other parts of the world where consumption of dairy and meat productions is low.

Question 9

Diseases and symptoms of riboflavin deficiency

Answer 9

Ariboflavinosis - inflammation of:

eyes

skin (seborrheic dermatitis becoming red, scaly and greasy)

lips (cheilosis)

mouth

tongue

Flavin deficiency can influence iron absorption and mobilization and as a consequence can affect the production and function of red blood cells.

Question 10

Miscellaneous facts about riboflavin

Answer 10

Riboflavin participates in the metabolism of other vitamins: pyridoxine, folic acid, and niacin.

Riboflavin is destroyed by light.

This explains why milk is not stored in glass bottles or clear plastic.

Question 11

What is Niacin and where is it found and forms

Answer 11

Vitamin B3

The coenzyme forms of niacin are nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP)

Niacin is found in meat and fish, legumes, bran, peanuts, enriched flour

Question 12

Reactions involving niacin

Answer 12

Electron carrier - oxidation/reductions.

Functions as either a coenzyme or substrate in energy metabolism

Glycolysis

TCA cycle

Electron transport chain

Also participates in breakdown and synthesis of fats, cholesterol synthesis, and many other reactions

Question 13

Niacin deficiencies

Answer 13

Pellagra (clinical 3D’s)

Diarrhea - mucosal inflammation/atrophy (contributes to further malnutrition)

Dermatitis - painful lesions (thick/scaly/pigmented), exacerbated by sun exposure

Dementia - delusions, mental confusion, anxiety, depression, insomnia. Can lead to death

Dietary deficiency - Niacin is unusual for a vitamin in that it can be synthesized in small amounts by the human body from the amino acid tryptophan.

Low amounts of tryptophan and poor bioavailability of niacin in unfortified corn appear to explain why niacin deficiencies are prevalent in regions of the world where corn is a dietary staple.

Pellagra was endemic in the Southeastern USA in the early 1900’s due to the heavy reliance on corn as a dietary staple of the poor.

Niacin deficiency has also been observed in individuals with Hartnup’s disease (neutral amino acid transporter) due to the inefficient absorption of tryptophan from the gut and reabsorption in the kidney.

Question 14

Niacin random facts

Answer 14

Niacin has been used to reduce cardiovascular events and mortality in patients with cardiovascular disease

Skin flushing is a common side effect of pharmacological doses of niacin. Itching and GI side effects have also been observed.

Question 15

What is biotin and source

Answer 15

Vitamin B7

Biotin is found in liver, egg yolks, yogurt and nuts. Also made by interstitial bacteria

Question 16

Reactions involving biotin

Answer 16

Biotin is only used for carboxylation reactions.

Biotin is needed for:

Gluconeogenesis (pyruvate carboxylase)

Fatty acid synthesis (acetyl-CoA carboxylase)

and the catabolism of certain amino acids (propionyl-coA carboxylase and methylcrotonyl-carboxylase)

Question 17

Biotin deficiencies

Answer 17

Usually acquired, not dietary unless feeding tube

Egg whites (uncooked) contain a protein known as avidin that binds biotin very tightly. The binding of avidin to biotin prevents biotin’s absorption thereby inducing a deficiency.

Inborn errors of metabolism - for enzymes to use biotin effectively it must be liberated from natural sources by biotinidase and then covalently bonded to relevant enzymes through the action of holocarboxylase synthase.

A deficiency of either of these enzymes can cause multiple carboxylase deficiency caused by ineffective utilization of dietary biotin.

Symptoms of multiple carboxylase deficiency are much more severe than dietary biotin deficiencies.

Symptoms: brittle fingernails, hair loss, skin rashes, neurological deficits, and tingling of the extremities

Question 18

What is pantothenic acid and source

Answer 18

Vitamin B5

Pantothenic acid is a component of Coenzyme A and serves as a acyl carrier in fatty acid and cholesterol metabolism

widely distributed in foods

Question 19

Reactions involving pantothenic acid

Answer 19

Pantothenic acid functions as an acyl carrier, acetyl-CoA being the most familiar, various other CoA derivatives are found in nature

Question 20

Pantothenic acid deficiencies

Answer 20

Causes

Specific dietary deficiencies of pantothenic acid are rare but have been reported in severely malnourished prisoners in the Pacific Theater during World War II.

Pantothenic acid deficiency is also a likely contributing factor to symptoms evident in alcoholics with multiple vitamin B deficiencies.

Symptoms

Pantothenic acid deficiency is characterized by numbness and painful burning and tingling in extremities.

Question 21

Pyridoxine and source

Answer 21

Vitamin B6

Pyridoxine is found in both animal and plant products including meats, whole grains, brown rice and some fruits and vegetables.

Pyridoxine is inactivated by heat and light; therefore it is not used to fortify grain products but is used to fortify breakfast cereals.

Question 22

Reactions involving pyridoxine

Answer 22

Transamination reactions – all transaminase enzymes use pyridoxal phosphate as a coenzyme.

Several enzymes involved in human disorders use pyridoxal phosphate as a coenzyme and some of these patients may respond to vitamin supplementation.

X-linked sideroblastic anemia - enzyme affected, δ-amino levulinic acid synthase, defect in heme synthesis

Homocysteinuria - enzyme affected, cystathionine synthase, defect in methionine catabolism

Ornithineamia with gyrate atrophy - enzyme affected, ornithine δ-aminotransferase, transaminase involved in the inter-conversions of ornithine-glutamic acid-proline

Pyridoxine-dependent epilepsy - enzyme affected, α-aminoadipic semialdehyde dehydrogenase, which is involved in breaking down lysine in the brain

Hypophosphatasia - non-tissue-specific alkaline phosphatase, needed for pyridoxal entry into the brain. The disease is characterized by convulsions and epilepsy.

Pyridoxal phosphate is involved in many different aspects of neurotransmitter metabolism.

Question 23

Causes of pyridoxine deficiency

Answer 23

Nutritional deficiencies of pyridoxine are rare except in alcoholics.

Drug interactions - certain drugs can inactivate pyridoxine and its derivatives.

These drugs can therefore induce a B6 deficiency.

B6 supplements are often recommended when using these drugs to avoid neuropathy and other symptoms of B6 deficiency.

Cycloserine - tuberculosis

Isoniazid - tuberculosis

Hydralazine - high blood pressure

Theophylline - asthma

Penicillamine - rheumatoid arthritis

Monoamine oxidase inhibitors - depression

L-DOPA used in treating Parkinson’s may also limit the bioavailability of B6

Pyridoxine is destroyed by heat and light, so there have been reports of acquired B6 deficiencies.

Question 24

Symptoms of pyridoxine deficiency

Answer 24

Neurological features - Infants consuming the formula where B6 was inactivated by heat as a major food source began displaying abdominal problems, convulsions and other neurological symptoms.

Symptoms in these children were reversed when their diet was supplemented with B6.

Neurological features of B6 deficiency are thought to relate to its role in neurotransmitter synthesis and include:

Confusion

Depression

Headaches

Numbness or tingling in extremities, and seizures.

Anemia - microcytic anemia with ringed sideroblasts

Seborrheic dermatitis

Glossitis

Cheilosis

Question 25

Pyrisoxine toxicity and drug interaction

Answer 25

Toxicity: Long term supplementation with very high doses of B6 (1,000 mg/day) has been shown to induce sensory neuropathy

Interactions: High doses of B6 have been shown to reduce the efficacy of phenobarbital, phenytoin, and L-DOPA by increasing metabolism

Question 26

Pyridoxine random info

Answer 26

B6 supplementation may be of some use in treating morning sickness, premenstrual syndrome, and depression

Little evidence supports the use of B6 supplements to treat carpal tunnel syndrome - despite claims to the contrary

Many studies have examined the role of B6 supplementation in disease prevention including: immune dysfunction, cardiovascular disease, cognitive decline, cancer, and kidney stones.

Question 27

What is folate and source

Answer 27

Vitamin B9

Folate is rich in lentils and certain green vegetables.

It is found in smaller amounts in many other foodstuffs - refined grain (increased bioavailability)

Question 28

Reactions that involve tetrahydrofolate

Answer 28

Formyl-tetrahydrofolate – purine synthesis

N5,N10-methylene-tetrahydrofolate – thymidine synthesis

N5-methyl-tetrahydrofolate – methionine synthesis from homocysteine.

N5-methyl-tetrahydrofolate in the monoglutamate form is the means by which folate in the diet is transferred in the circulation

Once taken into cells, N5-methyl-tetrahydrofolate is converted to tetrahydrofolate by the methionine synthase reaction, which also requires methyl-cobalamin.

The tetrahydrofolate produced in this manner gets polyglutamated, which prevents it from being released from cells.

Tetrahydrofolate then gets converted to the other forms active in one carbon metabolism

Because of its central role in nucleotide synthesis, folate is particularly important for dividing cells and pregnant woman have a significantly higher folate requirement than other adults.

Growing children also have increased requirements for folate.

Question 29

Folate deficiencies causes

Answer 29

Dietary deficiencies of folate were fairly common before foods became fortified.

Folic acid deficiency is also observed with chronic alcoholism.

Question 30

Folate deficiency diseases and symptoms

Answer 30

Megaloblastic anemia – dietary deficiencies of folate typically manifest as a megaloblastic anemia due to the need for nucleotides in the rapid proliferation of red blood cells. This is a macrocytic anemia, as cells continue to grow even while division is delayed because replication has slowed.

Neural tube defects – folate deficiency has been associated with spina bifida, anencephaly and other neural tube defects. This relationship is not absolute, suggesting that other factors besides folate contribute to these defects. Nevertheless, the incidence of neural tube defects has gone down after the government mandated that refined grains be fortified with folic acid.

Elevated homocysteine – 5-Methyltetrahydrofolate is needed for recycling methyl-B12 during the methionine synthase reaction and so a folate deficiency can lead to elevated homocysteine levels. Since elevated homocysteine is associated with cardiovascular disease there is considerable interest in whether folate deficiency is a contributing factor to cardiovascular disease.

Question 31

What is the folate trap

Answer 31

A vitamin B12 deficiency traps folate in the N5-methyl-tetrahydrofolate state.

With B12 unavailable to convert N5-methyl-tetrahydrofolate to tetrahydrofolate, the amount of usable folate in cells drops (as it is trapped as N5-methyl-tetrahydrofolate) leading to a macrocytic anemia for the reasons discussed above.

Folic acid supplementation can rescue the anemia associated with B12 deficiency but does not rescue the neurological features of B12 deficiency

Question 32

How can 5-methyl-tetrahydrofolate treat depression

Answer 32

5-methyl-tetrahydrofolate is the main transport form of folic acid in the circulation and is capable of crossing the blood brain barrier.

5-methyl-tetrahydrofolate provides a methyl group for the synthesis of methionine from homocysteine in a reaction catalyzed by methionine synthase, which requires cobalamin as a co-enzyme (see discussion of cobalamin below).

The methyl group of methionine can be transferred to S-adenosyl-homocysteine to form S-adenosyl-methionine, which is another major methyl group donor in the body.

S-adenosyl-methionine is used in the synthesis of monoamine neurotransmitters, and methylation disorders of the nervous system have been linked to depression.

Question 33

What is cbalamin and coenzymes abnd sources

Answer 33

Vitamin B12

The coenzyme forms of cobalamin are methyl-cobalamin and adenosyl-cobalamin.

Cobalamin is found almost exclusively in animal products, therefore vegans need to obtain cobalamin through fortified foods or supplements.

Question 34

Reactions that involve cobalamin

Answer 34

Methionine synthase - methyl-cobalamin is used to methylate homocysteine to methionine by the enzyme methionine synthase.

Cobalamine formed in this reaction is converted back to methyl-cobalamine by the same enzyme using N5-methyl-tetrahydrofolate as a methyl group donor.

Since this is the only reaction where N5-methyl-tetrahydrofolate is converted to tetrahydrofolate and returned to the folate pool, this reaction forms the basis for the folate trap

Methylmalony-CoA-Mutase - adenosyl-cobalamin participates in this mutase reaction where methylmalonyl-CoA is rearranged to succinyl-CoA in a late step in the catabolism of certain amino acids and odd-chain fatty acids

Question 35

Causes of cobalamin deficiency

Answer 35

Dietary deficiency – dietary deficiencies tend to be rare as the body stores and recycles B12.

Vegans, however, are at risk for B12 deficiency

Malabsorption – It contrast to dietary deficiencies, deficiencies of B12 can develop more quickly when they are caused by malabsorption problems as these problems can also affect recycling. Can be caused by pernicious anemia (Autoimmune process destroys parietal cells involved in the synthesis of intrinsic factor needed for B12 absorption in the ileum), atropic gastritis (low acid secretion), malabsortpion syndromes, resections

Drug interactions - PPIs, NO, Metformin, tetracycline

Question 36

Clinical features of cobalamin deficiency

Answer 36

Macrocytic anemia – caused by the folate trap where a cobalamin deficiency ultimately prevents N5-methyl-tetrahydrofolate from being converted to other usable forms of tetrahydrofolate and thereby depleting the body of usable folate derivatives.

Homocysteinuria - Methyl-B12 is required for the methionine synthase reaction converting homocystein to methionine. So a cobalamin deficiency can lead to elevated homocysteine levels.

Neuro manifestations -

numbness and tingling of hands and feet

difficulty walking

memory loss

disorientation

dementia

Question 37

How does cobalamin deficiency cause neuro side effects

Answer 37

The neurological manifestations likely reside in its role as an essential co-enzyme for the methionine synthase reaction.

Folic acid crosses the blood-brain barrier as 5-methyl-tetrahydrofolate

Upon entering neurons 5-methyl-THF is converted to THF via the methionine synthase reaction, with cobalamin as an essential co-enzyme.

Through this reaction, a methyl group is transferred first to cobalamin and then homocysteine to form methionine.

The methyl group of methionine can then be transferred to S-adenosyl-homocysteine to form S-adenosyl-methionine. S-adenosyl-methionine is required for myelin synthesis and neuronal integrity.

Methyl groups of choline are derived from S-adenosyl-methionine.

Choline is transferred from phosphatidylcholine to ceremide in forming sphingomyelin.

S-adenosyl-methionine is also required for the synthesis of certain neurotransmitters.

It is therefore thought that the neurological manifestations of cobalamin deficiency likely reside in its critical role in supplying precursors for S-adenosyl-methionine synthesis in the brain.

Question 38

What is ascorbic acid and source

Answer 38

Vitamin C

Ascorbic acid is rich in citrus fruits and many other fruits and vegetables.

Meats and grains however are a poor source of ascorbic acid.

Ascorbic acid is destroyed by exposure to oxygen, light and heat.

Spoiled fruits and vegetables are ineffective sources of ascorbic acid

Question 39

Reactions involving ascorbic acid

Answer 39

Hydroxylation reactions - Ascorbic acid is an electron donor and serves as a source of electrons for dioxygenases involved in hydroxylation reactions.

Hydroxylation of proline and lysine in collagen

Hydroxylation of dopamine to norepinephrine

Hydroxylation of hypoxia inducible factor used as an oxygen sensor in angiogenesis

Antioxidant - ascorbic acid is an important antioxidant protecting the body from reactive oxygen species.

Question 40

Causes of ascorbic acid deficiency

Answer 40

Scurvy

Inadequate fresh fruits and vegetables in the diet – historically groups that traveled over large distances

Question 41

Clinical features of ascorbic acid deficiency

Answer 41

Fragile blood vessels; pinpoint hemorrhages, bleeding gums, bruising

Poor wound healing

Bone fractures

Loose teeth

Joint pain and swelling

Question 42

Ascorbic acid misc

Answer 42

Ascorbic acid can increase iron absorption from the GI tract

Ascorbic acid has been used to prevent or treat everything from cancer to the common cold, mostly through its effects as an antioxidant and by stimulating the immune system.

Question 43

How are fat soluble vitamins absorbed

Answer 43

They are solubilized in the GI tract by bile and other fats, which is necessary for their absorption into the body.

Fat-soluble vitamins are absorbed into mucosal cells in micelles where they are then packaged into chylomicrons.

Chylomicrons deliver their contents to the liver, where fat-soluble vitamins can be repackaged and delivered to other tissues by various other binding proteins.

Question 44

What are vitamin A derivatives and source

Answer 44

Vitamin A

Preformed retinoids - can be found in foods from animal sources like liver, fish, egg yolks and dairy products.

Carotenoids - Vegetable and fruits have yellow/orange pigments known as carotinoids that can be converted into retinoids in mucosal cells of the liver.

Question 45

Involvement of retinoids in visual cycle

Answer 45

The visual cycle – the structure of retinal is a six-membered ring with a hydrocarbon tail, in many ways similar to a fatty acid, except for retinal with an aldehyde group at its terminus.

The hydrocarbon tails have a number of double bonds, must of which are found in the trans configuration giving the hydrocarbon tail an extended structure.

The exception is the double bond in the 11-position near the aldehyde-containing end. This double bond is cis, and so introduces a kink in the structure.

Upon absorbing a photon of light the cis double bond is isomerized to a trans configuration causing it to straighten and align with the rest of the hydrocarbon tail.

The conformational change in retinal is transmitted to opsin, a G protein coupled receptor to which the retinal is bound.

Opsin then undergoes its own conformational change and signals to its associated G protein, which then transmits information to the brain.

After signaling the all-trans retinal goes from the photoreceptor cell to the pigment epithelium where it is converted back to 11-cis retinal and returned to the photoreceptor cell.

Question 46

retinoids involvment in signal. transduction

Answer 46

Signal transduction – retinoic acid derivatives (all-trans-retinoic acid, 9-cis-retinoic acid) are retinoids involved in controlling gene expression at the transcriptional level.This regulation occurs through retinoic acid receptors that function as transcription factors.Via this regulation, retinoic acid controls both cell fate and function.

Development – retinoic acid derivatives play critical roles in human development affecting the formation of the cardiovascular system, nervous system, respiratory system and skeletal growth.

Immune system – retinoic acid derivatives control cell fate decisions during erythropoiesis.

Epithelial tissue – retinoic acid plays a role in the differentiation of epithelial layers.

Eyes – mucus secreting cells of the eye require retinoic acid signaling for appropriate function

Skin - retinoic acid plays in important role in controlling the differentiation of hair follicles and mucus secreting glands.

Bone growth and remodeling

Question 47

Causes of vitamin A deficiencies

Answer 47

Inadequate dietary sources of readily absorbed, pre-formed retinoids (typically from animal products).

Inadequate fat intake – limits solubilization of retinoids in the gut

Inadequate dietary protein/amino acids – needed for retinol binding protein involved in transporting retinoids from the liver to other tissues.

Inadequate zinc - can also interfere with retinoid metabolism and distribution within the body.

Question 48

Clinical features of vitamin A deficiency

Answer 48

Xerophthalmia - a spectrum of eye problems linked to vitamin A deficiency including: night blindness, extreme dryness and softening of the cornea referred to as keratomalacia. If untreated cornea ulcers/scarring, infection and tissue degeneration can lead to permanent blindness. It is estimated that 250,000-500,000 children go blind each year because of vitamin A deficiency and is the leading cause of preventable blindness worldwide.

Susceptibility to infectious diseases - because of the role of vitamin A in controlling hematopoiesis, vitamin A deficiency is considered a nutritionally acquired immunodeficiency disease.

Follicular hyperkeratosis - hard dry skin surfaces with lesions that appear on extremities, shoulders, and buttocks. Disruption of the skin barrier can lead to infections.

Vitamin A deficiency can also influence iron mobilization and so lead to microcytic anemia.

Question 49

Vitamin A toxicities

Answer 49

Excess preformed retinoids (NOT carotenoids because of their inefficient absorption) are toxic

Adults

Acute - nausea, headache, blurred vision, cerebral edema, and lack of muscle coordination

Chronic – weight loss, muscle and joint pain, liver damage, bone abnormalities, visual defects, anemia, and skin rashes

Infants

bulging frontanels

Pregnancy

Excess consumption of preformed retinoids during pregnancy can cause birth defects (retinoids are teratogens)

Question 50

What drug treatments use retinoids

Answer 50

Acute promyelocytic leukemia – APL is caused by reciprocal chromosomal translocations involving the PML gene and the retinoic acid receptor α in myeloid progenitor cells. This translocation interferes with normal differentiation resulting in the proliferation of immature blasts resulting in leukemia. The fusion protein has an altered affinity for all-trans-retinoic acid, which can be overcome by high doses of the drug resulting in forced differentiation of the leukemic clones and in some patients a complete remission.

Psoriasis – Acitritin is a synthetic retinoid used in treating psoriasis. Acitritin is an oral drug, which has a half-life of 2 days. However, it can be metabolized to a retinoid derivative with a much longer half-life and therefore should not be taken by woman planning to get pregnant within 3 years.

Severe Acne/Acne Vugarus - Isocitretinoin (13-cis-retinoic acid, acutane) – isocitretinoin, like other retinoids, is a tetratogen and there are strict controls on prescribing to woman who might become pregnant.

Retinitis pigmentosa – there is some evidence to suggest that supplementation with retinoids may significantly slow the loss of retina function.

Question 51

What is hypercarotenemia

Answer 51

Hypercarotenemia - most vitamin A supplements are carotenoids that are absorbed much less efficiently than pre-formed retinoids and so carry less risk of toxicity.

Large daily doses of carotenoids can cause hypercarotenemia, where large amounts of carotenoids stored in fat give skin a yellow/orange color.

This condition is reversible when supplements are discontinued.

Question 52

Cholecalciferol and source

Answer 52

Vitamin D

It is made in the skin via the action of sunlight on 7-dehydro-cholesterol.

There are only a few significant natural sources of vitamin D in the diet and these generally include animal derived products like salmon, liver, and egg yolks.

In the US, major sources of vitamin D in the diet come from fortified milk and cereals.

Question 53

How is vitamin D synthesized

Answer 53

7-dehydro-cholesterol is derived from cholesterol and converted to vitamin D3 (cholecalciferol) by a series of molecular rearrangements induced by sunlight (ultraviolet B radiation) in the skin and subsequent hydroxylation at the 25 position in the liver.

This form of vitamin D is inactive.

Activation of vitamin D3 occurs by a second hydroxylation at position 1 carried out by an enzyme in the kidney.

1,25-dihydroxy vitamin D3 is the active form of vitamin D. Vitamin D derivatives are transported through the circulation bound to the vitamin D binding protein and to a lesser extent by albumin.

Question 54

Reactions that involve vitamin D

Answer 54

Vitamin D behaves as a hormone rather than a vitamin-based co-enzyme.

Vitamin D plays a major role in regulating levels of calcium and phosphorous in the blood and so plays a central role in bone metabolism.

In response to low calcium, the parathyroid releases parathyroid hormone which stimulates the activity of kidney hydroxylase involved in converting 25-hydroxy vitamin D3 to 1,25-dihydroxy vitamin D3.

Question 55

Role of vitamin D in calcium and phosphorus

Answer 55

Active vitamin D binds to nuclear receptors and targets gene expression (through vitamin D response elements) in responsive tissues to increase blood calcium

Low levels of active vitamin D act on the intestine to increase Ca2+ transport proteins to facilitate Ca2+ uptake from the diet.

Active vitamin D also acts on the kidney to stimulate Ca2+ reabsorption

In the absence of dietary Ca2+, higher levels of active vitamin D mobilize Ca2+ from bone

Active vitamin D plays a similar role in phosphorous homeostasis

Question 56

Causes of vitamin D deficiences

Answer 56

Environmental conditions – latitude, length and strength of sunlight exposure

Clothing than covers all skin blocking exposure to sunlight

Sunscreens and other protection measures taken to reduce the risk of sunburn and skin cancer

Infants who are exclusively breast fed and receive limited vitamin D fortification are at risk for vitamin D deficiency, especially if they have limited exposure to sunlight

Individuals with darker skin tend to synthesize less vitamin D because skin pigments absorb light energy, limiting the amount of energy available for rearranging 7-dehydro-cholesterol

Chronic kidney disease affects the formation of active vitamin D in the kidney

Fat malabsorption syndromes – individuals with cystic fibrosis tend to have low levels of vitamin D as do individuals with cholestatic and non-cholestatic liver diseases

Obesity – vitamin D can be absorbed into fat stores limiting its availability for other functions

Elderly – reduced capacity to synthesize active vitamin D with age and more limited exposure to sunlight, particularly institutionalized adults in nursing homes.

Genetics – various proteins involved in vitamin D synthesis and transport can influence the amount of vitamin D produced within the body.

Question 57

Vitamin D deficiencies

Answer 57

Rickets (children) – vitamin D deficiency reduces calcium uptake limiting the amount available for bone formation thereby causing abnormal bone growth. Rickets is characterized by narrow rib cages and bowed legs.

Osteomalacia (adults) – in adults where bones are already formed, vitamin D deficiency can weaken bones leading to fractures in weight-bearing bones. Osteomalacia can also promote osteoporosis or make it worse.

Question 58

Vitamin D toxicity

Answer 58

Vitamin D toxicity does not occur from natural sources as the synthesis of active forms of the vitamin is carefully regulated in the body.

There have been reported cases of vitamin D toxicity associated with over-supplementation.

Symptoms of vitamin D toxicity include high blood calcium and calcium depositions in blood vessels, kidney and cardiovascular system.

Question 59

Vitamin D drug interactions

Answer 59

Cholesterol sequesterants should not be taken at the same time as vitamin D supplements.

Drugs like phenytoin, carbamazepine and rifampin increase vitamin D catabolism.

Question 60

What is tocopherol and source

Answer 60

Vitamin E - fat soluble

There are several forms of vitamin E in foods but α-tocopherol is the active form of the vitamin.

Nuts and vegetable oils are good sources of vitamin E in the diet.

Question 61

Reactions involving vitamin E

Answer 61

The primary function of vitamin E is as a fat-soluble antioxidant.

Being fat-soluble vitamin E serves a critical function in neutralizing oxidatively damaged unsaturated fats in cell membranes, a function that cannot be effectively performed by water-soluble antioxidants. Protecting cell membranes from oxidative damage is of vital importance, particularly to red blood cells, nerves, and cells of the immune system.

Vitamin E also protects VLDLs and other lipoproteins from oxidation and so, are thought to be protective against cardiovascular disease.

Since vitamin E is oxidized in performing its antioxidant functions, it needs to be recycled, receiving electrons from other antioxidants like vitamin C.

Question 62

Causes of tocopherol deficiencies

Answer 62

Dietary deficiencies are rare but can be associated with malnutrition

Fat-malabsorption syndromes

Genetics – defects in α-tocopherol transfer protein needed for the transfer of α-tocopherol to lipoproteins for delivery to cells.

Birth – little transfer of vitamin E occurs from mother to fetus until late in pregnancy. Premature infants can have damaged red blood cell membranes and suffer from hemolytic anemia due to vitamin E deficiency.

Question 63

Symptoms of tocopherol deficiencies

Answer 63

Neurologic - impaired balance and coordination, damage to sensory nerves, muscle weakness, and damage to the eye (peripheral neuropathy, ataxia, and retinitis pigmentosa – classic symptoms)

Hemolytic anemia – see discussion above regarding premature infants

Question 64

Vitamin E drug interactions

Answer 64

Vitamin E supplements may inhibit the γ-carboxylation of clotting factors, so should not be taken with warfarin to reduce the risk of serious bleeding.

Cholesterol sequesterants should not be taken at the same time as vitamin E supplements

Drugs like phenytoin, carbamazepine and rifampin increase vitamin E catabolism

Question 65

What is phylloquinone and source

Answer 65

Vitamin K

The phylloquinones are rich in many leafy green plants and vegetable oils.

Some forms of vitamin K are also formed by bacteria within the digestive tract and absorbed.

Question 66

Reactions involving vitamin K

Answer 66

Active forms of vitamin K serve as an essential co-enzyme for γ-glutamyl carboxylase, which is the enzyme responsible for forming γ-glutamyl residues in coagulation factors.

This modification is essential for the full activity of coagulation factors.

Vitamin K is an electron donor in the reaction and is recycled back to the reduced state by vitamin K epoxide reductase (VKOR).

This recycling reaction is targeted by the anticoagulant warfarin.

Question 67

Causes of vitamin K deficiencies and symptoms

Answer 67

Dietary deficiencies are rare in adults, but are common in newborns as there is little transfer of vitamin K from mother to fetus and the newborn GI tract is essentially free of bacteria. Breast milk is also a relatively poor source of vitamin K. Most infants receive a vitamin K injection within 6 hours of birth.

Fat-malabsorption syndromes can affect vitamin K absorption

Antibiotics that kill off GI bacteria coupled with a diet low in vitamin K can lead to vitamin K deficiency.

Symptoms: Bleeding