Water-Soluble Vitamins Flashcards

1
Q

The only glucose-derived vitamin

A

Ascorbic acid (Vitamin C)

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2
Q

What is the role of ascorbic acid in collagen synthesis?

A

Ascorbate (anion of ascorbic acid) is the cofactor for prolyl hydroxylase (which hydroxylates proline in procollagen) and lysyl hydroxylase (which hydroxylates lysine in procollagen).

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3
Q

How does vitamin C deficiency cause poor wound healing?

A

Low vitamin C causes insufficient/defective collagen synthesis so that the break in the skin cannot be resealed fully.

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4
Q

How does vitamin C deficiency cause osteoporosis?

A

Organic bone matrix consists largely of collagen so low vitamin C can lead to defective bone formation.

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5
Q

How does vitamin C deficiency cause capillary fragility?

A

The ground substance of capillary walls contain collagen. With low vitamin C, less collagen is produced, weakening the capillary walls. This results to easy bruising, petechial hemorrhages in skin and mucous membranes.

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6
Q

How does vitamin C deficiency cause anemia?

A

Because vitamin C helps increase intestinal Fe absorption (by reducing Fe3+ to Fe2+), vitamin C deficiency can lead to Fe deficiency and anemia.

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7
Q

How does ascorbic acid increase intestinal Fe absorption?

A

It converts Fe3+ (ferric) to Fe2+ (ferrous), which is more readily absorbed in the intestines.

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8
Q

With regard to vitamin C consumption, why is it advisable to eat fruits and vegetables fresh?

A

Vitamin C in food is destroyed by overcooking and prolonged storage.

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9
Q

What is the role of vitamin C in catecholamine synthesis?

A

It is the cofactor in the conversion of dopamine to epinephrine:

  1. Tyrosine –> DOPA (3,4,-dihydroxyphenylalanine) via tyrosine hydroxyalse
  2. DOPA –> Dopamine via DOPA decarboxylase
  3. Dopamine –> Epinephrine via Dopamine beta-hydroxylase (WITH ASCORBIC ACID AS COFACTOR)
  4. Epinephrine –> Norepinephrine via phenylethanolamine N-methyl transferase with SAM (S-adenosylmethionine) as methyl donor.
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10
Q

True/False: It is common to have deficiency of a single vitamin.

A

False. Deficiency of a single vitamin is rare. Poor diets often associate with multiple deficiency states and overlapping symptoms.

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11
Q

True/False: Toxicities from vitamins are rare.

A

True. Vitamins are stored in tissue at low levels. Excess vitamins (those that exceed the renal threshold) are excreted.

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12
Q

What is the role of vitamin C in carnitine synthesis?

A

It acts as cofactor in the 4 reactions that convert epsilon-N-trimethyllysine to L-carnitine (preceeded by trimethylation of lysine).

  1. Lysine residues in proteins are trimethylated at the epsilon-amino group to make epsilon-N-trimethyllysine.
  2. WITH VITAMIN C AS COFACTOR, 4 steps follow that convert epsilon-N-trimethyllysine to L-carnitine.
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13
Q

How does vitamin C deficiency cause fatigue?

A

Vitamin C helps produce carnitine, which transports fatty acids from the cytosol to the mitochondria for beta oxidation. Fatty acid oxidation produces ATP. So without enough vitamin C, not enough ATP (energy) can be produced, hence the fatigue.

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14
Q

What is the role of vitamin C in tyrosine degradation?

A

It is a cofactor of p-hydroxyphenylpyruvate dioxygenase, which converts p-hydroxyphenylpyruvate to homogentisate.

  1. Tyrosine –> p-hydroxyphenylpyruvate via tyrosine aminotransferase (deaminated)
  2. p-hydroxyphenylpyruvate –> homogentisate via p-hydroxyphenylpyruvate dioxygenase WITH VITAMIN C AS COFACTOR
  3. Series of reactions that convert tyrosine into either acetoacetate (as a ketogenic amino acid) or fumarate (as a glucogenic amino acid).
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15
Q

What is neonatal tyrosinemia?

A

A disorder due to p-hydroxyphenylpyruvate dioxygenase. A benign condition in newborns; treated with dietary protein restriction and ascorbate supplementation (since enzyme requires ascorbate for its activity).

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16
Q

What happens when there is excess of vitamin C?

A

High excretion of kidney stones from calcium salt deposits of oxalate, a breakdown product.

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17
Q

It is the biologically active form of vitamin B1.

A

Thiamine pyrophosphate (TPP) or Thiamine diphosphate (TDP).

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18
Q

How is TPP formed?

A

PPP synthase transfers a phosphate group from ATP to thiamine.

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19
Q

What is the role of TPP in PPP (pentose phosphate pathway)?

A

It is a cofactor in the transketolation reactions (non-oxidative stage of PPP):

  1. Transketolation between xylulose 5-PO4 and ribose 5-PO4 to form seduheptulose 7-PO4 and glyceraldehyde 3-PO4
  2. Transketolation between xylulose 5-PO4 and erythrose 4-PO4 to form glyceraldehyde 3-PO4 and fructose 6-PO4.
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20
Q

What is the role of TPP in TCA?

A

TPP is a cofactor of the various dehydrogenases in the oxidative decarboxylations of the TCA:

  1. pyruvate –> acetyl CoA via pyruvate dehydrogenase
  2. isocitrate –> alpha-ketoglutarate via isocitrate dehydrogenase
  3. alpha-ketoglutarate –> succinyl CoA via alpha-ketoglutarate dehydrogenase
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21
Q

How does TPP deficiency impair cellular function?

A

Without the key energy-synthesizing pathways in TCA that uses TPP as cofactor, ATP won’t be formed. Low ATP levels impair cellular function.

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22
Q

How does TPP deficiency cause lactic acidosis?

A

TPP is a cofactor of pyruvate dehydrogenase, which converts pyruvate to acetyl CoA. TPP deficiency impairs this conversion so that there is accumulation of pyruvate. Since pyruvate is convertible to lactate (via lactatde dehydrogenase), lactate also accumulates. This could lead to lactic acidosis.

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23
Q

How does TPP deficiency cause peripheral neuropathy?

A

TPP is a cofactor in key energy-synthesizing pathways (TCA) that are also important in the CNS (since ATP used up in neuronal depolarization must be replenished). Actually, glutamate (a neurotransmitter), may be oxidized in nerve cells to yield alpha-ketoglutarate (a substrate in TCA). TPP deficiency therefore impairs nerve transmission in the neural tissue by lowering ATP synthesis.

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24
Q

How does TPP deficiency cause lactic acidosis?

A

TPP is a cofactor of pyruvate dehydrogenase, which converts pyruvate to acetyl CoA. TPP deficiency impairs this conversion so that there is accumulation of pyruvate. Since pyruvate is convertible to lactate (via lactatde dehydrogenase), lactate also accumulates. This could lead to lactic acidosis.

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25
Q

What is the role of TPP in the catabolism of branch-chained amino acids?

A

TPP is a cofactor of alpha-ketoacid dehydrogenase, which catabolizes branch-chain amino acids (valine, isoleucine, and leucine) by oxidative decarboxylation:

  1. valine, isoleucine –> succinyl CoA –> glucogenic precursor
  2. leucine –> acetyl CoA and acetoacetate –> ketogenic precursor
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26
Q

How is thiamine deficiency diagnosed?

A

RBC transketolase (enzyme) activity is low when there is TPP deficiency. Thus, accelerated RBC transketolase activity upon addition of TPP indicates a deficiency.

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27
Q

What is Wernicke-Korsakoff syndrome?

A

A thiamine deficiency associated with chronic alcoholism and drug abuse.

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28
Q

What is Beriberi?

A

A severe thiamine deficiency syndrome found among Asians whose staple food is rice. If the rice is well-polished (i.e. rice bran was removed), its thiamine content is depleted.

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29
Q

What is Wernicke-Korsakoff syndrome?

A

A thiamine deficiency associated with chronic alcoholism and drug abuse.

30
Q

What are the structural components of riboflavin (vitamin B2)?

A

As a flavin, vitamin B2 has isoalloxacin (a heterocyclic ring). At the N10 of isoalloxacin, ribitol (alcohol) is connected.

31
Q

How is FAD (flavin adenine dinucleotide) formed?

A

AMP from ATP is transferred to FMN.

32
Q

What is the role of FMN and FAD in redox reactions?

A

Both FMN and FAD are tightly bound as coenzymes to flavoenzymes (or flavoproteins) that catalyze redox reactions.

FMN is a component of NADH dehydrogenase, which accepts and donates electrons to other components of the ETC system.

FAD is a component of succinate dehydrogenase/glycerol 3-PO4 dehydrogenase, which also accept and donate electrons in the ETC.

33
Q

True/False: Severe vitamin B2 deficiency decreases mitochondrial ATP synthesis via oxidative phosphorylation.

A

True.
Vitamin B2 is a coenzyme in ETC reactions in mitochondria (site of oxidative phosphorylation in eukaryotes).
Low riboflavin –> low oxidative phosphorylation –> low ATP synthesis

34
Q

What is the role of FAD in the citric acid cycle?

A

FAD is the acceptor of 2 H+ atoms from succinate in the succinate dehydrogenase reaction of the CAC:

succinate –> fumarate
via succinate dehydrogenase

In the process, FAD is reduced to FADH2 (FADH+ + H+).

35
Q

What is the role of FAD in the beta-oxidation of fatty acids?

A

FAD is the electron acceptor in the 1st oxidation reaction of beta-oxidation:

palmitoyl CoA –> delta two-transenoyl CoA
via acyl CoA dehydrogenase

FAD is reduced to FADH2 in the process.

36
Q

What is the role of FAD and FMN in NO (nitric oxide) synthesis?

A

FMN and FAD are coenzymes (along with O2, tetrahydrobiotin/BH4, and heme) in the 5-electron oxidation of:

guanidine nitrogen (of arginine) --> citrulline and NO
via NO synthase
37
Q

What is the role of FAD in the beta-oxidation of fatty acids?

A

In the 1st oxidation reaction,
an activated fatty acid (like palmitoyl CoA) –> delta two-transenoyl CoA via acyl CoA dehydrogenase WITH FAD AS ELECTRON ACCEPTOR. FAD is reduced to FADH2 in the process.

38
Q

What is the role of FAD and FMN in NO (nitric oxide) synthesis?

A

In the presence of O2, FAD, FMN, heme, and tetrahydrobiotin (BH4) as coenzymes, NO synthase catalyzes the 5-electron oxidation of guanidine nitrogen (of arginine) –> citrulline and NO.

39
Q

What is the role of FMN in the deamination of amino acids?

A

FMN is a a coenzyme of L-amino acid oxidase (liver and kidney), which deaminates L-amino acids.

L-amino acids –> alpha-keto acids, NH4+, H2O
via L-amino acid oxidase

40
Q

What are the classic riboflavin deficiency symptoms?

A
  1. Dermatitis - seborrhea (“greasy” dermatitis)
  2. Cheilosis - inflammation & fissuring at corners of mouth
  3. Glossitis - ligual desquamation with smooth and purplish color of the tongue (magenta tongue)
41
Q

What are the biologically active forms of niacin (nicotinic acid or vitamin B3)?

A
  1. Nicotinamide adenine dinucleotide (NAD+)

2. Nicotinamide adenine dinucleotide phosphate (NADP+)

42
Q

Why is niacin not strictly a vitamin?

A

Dietary requirements for niacin can easily be met by tryptophan, its precursor.

43
Q

1 mg dietary niacin = ? mg tryptophan

A

1 mg dietary niacin = 60 mg Trp

44
Q

Why is the conversion of tryptophan to niacin an inefficient process?

A

It occurs only after all body requirements for tryptophan are met.

45
Q

What is the role of NAD+ in redox reactions?

A

In the CAC, NAD+ is a hydrogen acceptor in redox reactions (isocitrate, alpha-ketoglutarate, malate dehydrogenases).
It is reduced to NADH2 (NAD+ + H+) in the process. It then donates these electrons to the ETC.

NAD+ is a cofactor of dehydrogenases in redox reactions.

46
Q

What is the role of niacin in lipid metabolism?

A
  1. It lowers LDL cholesterol and TAG by noncompetitive inhibition of liver diacylglycerol transferase-2 (enzyme in TAG synthesis)
  2. It elevates HDL cholesterol by inhibiting the removal of HDL particles from the circulation.
47
Q

What is pellagra?

A

Deficiency of tryptophan and niacin.
“Rough skin” (italian)
Affects skin, GIT, CNS.
3Ds: dermatitis - diarrhea - dementia - (death if untreated)

48
Q

What is Hartnup disease?

A

Genetic disorder wherein there is a defect in the transport mechanism for tryptophan, causing low intestinal and renal absorption.

Thus, pellagra develops in spite of getting enough tryptophan and niacin.

49
Q

How can niacin be used in the treatment of hyperlipidemia?

A

High doses of niacin (100x RDA) inhibits adipose tissue lipolysis.

50
Q

What is the active form of biotin?

A

Carboxy-biotin (if there is attached CO2).

51
Q

What is the role of biotin in carboxylation reactions?

A

Biotin is a carrier of activated CO2 (as HCO3-) in carboxylation reactions:

  1. pyruvate carboxylase (gluconeogenesis)
  2. acetyl CoA carboxylase (de novo FA synthesis)
  3. propionyl CoA carboxyalse (heme synthesis)
  4. beta-methylcrotonyl CoA carboxylase (catabolism of leucine)
52
Q

Why is biotin deficiency rare in humans?

A

It is required is such small amounts.

It is synthesized by intestinal bacteria in excess of requirements.

53
Q

Why did a man who ate mostly peanuts and raw white eggs develop biotin deficiency?

A

Uncooked egg white contains avidin, which binds biotin and prevents its intestinal absorption.

54
Q

Being a component of coenzyme A, what is the function of pantothenic acid?

A

It functions in the transfer of acyl groups (because of its thiol -SH group)

55
Q

What is the role of pantothenic acid in fatty acid elongation?

A

Pantothenic acid forms part of the ACP (acyl carrier protein), the component of fatty acid multienzyme complex that holds the growing FA chain during elongation.

56
Q

What is the other name for folic acid?

A

Pteroyl Glutamate

57
Q

What is the active form of folic acid?

A

Tetrahydrofolate (FH4)

58
Q

Arrange the following interconversions of one-carbon units of FH4 from most oxidized to most reduced:

N5,N10-methenyl FH4
N5-methyl FH4
N10-formyl FH4
N5,N10-methelyn FH4

A

N10-formyl FH4 (most oxidized folate derivative)
N5,N10-methenyl FH4
N5,N10-methelyn FH4
N5-methyl FH4 (most reduced folate derivative)

59
Q

What is the primary source of one-carbon units for FH4?

A

N5,N10-methylene FH4

60
Q

What is the role of N5,N10-methylene FH4 in the synthesis of serine from glycine?

A

N5,N10-methylene FH4 carries the hydroxy-methyl group that is reversibly transferred by serine hydroxymethyl transferase from glycine to form serine.

In the process, N5,N10-methylene FH4 is converted to FH4.

61
Q

True/False: FH4 is the primary one-carbon carrier in lipid metabolism.

A

False. FH4 is the primary one-carbon carrier in protein metabolism.

62
Q

What is the role of N5-methyl FH4 in the synthesis of methionine from homocysteine?

A

N5-methyl FH4 carries the methyl group that is transferred by methionine synthase (cofactor vit. B12) from homocysteine to form methionine.

63
Q

What is the role of N5,N10-methylene FH4 in the synthesis of dTMP (deoxythymidine monophosphate) from dUMP (deoxyuridine monophosphate)?

A

N5,N10-methylene FH4 is the source of the methyl group that is used by thymidylate synthase to convert dUMP to dTMP.

64
Q

What is the role of N5,N10-methenyl FH4 in purine nucleotide synthesis?

A

N5,N10-methenyl FH4 is the carbon atom donor used by formyl transferase to formylate glycinamide ribosyl-5-phosphate into formylglycinamide ribosyl-5-phosphate.

65
Q

What is the role of N10-formyl FH4 in purine nucleotide synthesis?

A

N10-formyl FH4 is the carbon group donor used by formyl transferase to formylate amidoimidazole caboxamide ribosyl 5-phosphate into formimidoimidazole caboxamide ribosyl-5-phosphate.

66
Q

What are the contributions of FH4 to the atoms of the purine ring?

A

C8 from N5,N10-methenyl FH4

C2 from N10-formyl FH4

67
Q

How does the folic acid inhibitor 5-fluorouracil (FU) work as a chemotherapeutic agent?

A

As a pyrimidine analog, FU is converted into dfUMP and competes with dUMP for the active site of thymidylate synthase, which converts dUMP to dTMP.

The formation of an irreversible enzyme-dfUMP-FH4 ternary complex traps the enzyme. Thus, dTMP, which is needed for DNA synthesis cannot be formed.

no dTMP –> no DNA synthesis –> no cell division
–> no tumor growth

68
Q

How does the folic acid inhibitor methotrexate work as a chemotherapeutic agent?

A

As a folate analog, methotrexate competes with FH2 for the active site of difydrofolate reductase, which converts FH2 to FH4.
FH4 supply not replenished –> cancer cells stop multiplying –> cancer remission

69
Q

How can folic acid deficiency cause megaloblastic anemia?

A

low dTMP –> DNA synthesis is inhibited –> arrest of cells at S phase –> no cell division –> accumulation of abnormally large, immature, RBC precursors (megaloblasts) –> megaloblasts have fragile membranes –> anemia

70
Q

How does folic acid deficiency cause spina bifida and anencephaly?

A

Spina bifida and anencephaly are neural tube defects.
Genetic deficiency of N5,N10-methylenetetrahydrofolate reductase (which makes N5,N10-methyl tetrahydrofolate) leads to accumulation of homocysteine and folate deficiency.
Folate deficiency –> inhibition of DNA synthesis –> neural tube defects