Vitamins I

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Vitamins I
MOL 114
Dr Hanaa Hajeer
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Lecture Learning Outcomes

At the end of this lecture, students should be


able to:
• List the water- and Fat-soluble vitamins
• Describe the function of vitamins
• Understand vitamin toxicity
• Understand vitamin deficiencies
Vitamins
• Vitamins are organic compounds necessary in small
amounts for the normal growth and function of humans
and some animals.
• Vitamins are necessary components of healthy diets and
play important roles in cellular metabolism.
• Vitamins are considered “micronutrients.”
• Although these substances occur in only very small
amounts within cells, they are critically important.
• Their absence is usually manifested as some deficiency
disease.
• The term vitamin was first used to describe the “vital
amine,” thiamine, which is needed to prevent beriberi.
• “Vitamin” as a generalized name survived.
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Water Soluble vitamins
• Vitamins B complex and C
• They are not stored in the body
• When consumed in excess are eliminated in the
urine
• So deficiency may be more of a concern than
toxicity
• Exceptions are B12 and folate (stored in liver)
• Play role as coenzymes
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Water-soluble Vitamins
• B1 (thiamine: TPP)
• B2 (riboflavin: FAD and FMN)
• B3 (niacin: NAD+)
• B5 (pantothenic acid: CoA)
• B6 (pyridoxine: PLP)
• B12 (cobalamin)
• C (ascorbic acid)
• biotin
• folate
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B1/ Thiamine
• B1(Thiamine) is precursor for Thiamine
pyrophosphate (TPP)
• TPP is a cofactor for several enzymes :
1. Pyruvate dehydrogenase (after glycolysis)
TLCFN
2. α-ketoglutarate dehydrogenase (TCA cycle)
TLCFN
3. Branched-chain ketoacid dehydrogenase
(metabolism of Val, Leu, Ile) TLCFN
4. Transketolase (HMP shunt)
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B1 / Thiamine Deficiency
Causes:
1. alcoholism
• most common cause in US
• Ethanol interferes with thiamine absorption in small
intestine
2. malnutrition
• non-enriched rice
Consequences:
• impaired glucose breakdown due to decreased
activity of pyruvate dehydrogenase
• leads to ATP depletion
• highly aerobic tissues are affected first
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B1 / Thiamine Deficiency
• Deficiencies lead to disease
called Beriberi (neurological
disorders)
• Beriberi prevalent in
undeveloped countries where
white rice make up the majority
of the diet.
• Associated with alcohol related
disorders (Wernicke-Korskofff
syndrome – memory loss,
unstable walk)
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B1 / Thiamine Deficiency
• Patients that present with thiamine deficiency
should be treated with thiamine first
• After thiamine has been administered, can then
administer glucose in IV fluids
• Administering glucose before thiamine could
exacerbate Wernicke-Korsakoff syndrome
• If glucose given first → unable to metabolize
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Water-soluble Vitamins
• B1 (thiamine: TPP)
• B2 (riboflavin: FAD and FMN)
• B3 (niacin: NAD+)
• B5 (pantothenic acid: CoA)
• B6 (pyridoxine: PLP)
• B12 (cobalamin)
• C (ascorbic acid)
• biotin
• folate
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B2 (Riboflavin: FAD and FMN)

• B2 (Riboflavin) is a precursor for FAD and FMN


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B2 (Riboflavin: FAD and FMN)

• Riboflavin is a
cofactor for
dehydrogenases:
• Succinate
dehydrogenase
(TCA)
• TLCFN enzymes
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B2 / Riboflavin Deficiency
• Causes: severe malnourishment
• Symptoms:
• cheilosis (inflammation of the lips and scaling and
fissures at the corners of the mouth)
• magenta-colored tongue (glossitis)
• corneal vascularization
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Water-soluble Vitamins
• B1 (thiamine: TPP)
• B2 (riboflavin: FAD and FMN)
• B3 (niacin: NAD+)
• B5 (pantothenic acid: CoA)
• B6 (pyridoxine: PLP)
• B12 (cobalamin)
• C (ascorbic acid)
• biotin
• folate
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B3/ Niacin
• Required in relatively high amounts compared to
other vitamins
• B3 (Niacin or Nicotinic Acid) is precursor for
Nicotinamide adenine dinuceotide (NAD)
• NAD is component of NADH, NADPH
• NADH & NADPH are cofactors for several
dehydrogenases, including TLCFN, G6PD
• NADH is coupled with ATP production in
mitochondria
• NADPH is an important reducing agent in
biosynthetic reactions
O O

C C
OH NH2

B3/ Niacin Deficiency N


NICOTINIC ACID
N

NICOTINAMIDE
(NIACIN)

 B3 can also be synthesized from tryptophan in the liver


 Vitamin B3 deficiency can result in Pellagra (Dermatitis,
Diarrhea, Dementia)
B3/ Niacin Toxicity

 B3 is given at high doses as


treatment for hyperlipidemia
 Symptoms of toxicity : facial flushing
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Water-soluble Vitamins
• B1 (thiamine: TPP)
• B2 (riboflavin: FAD and FMN)
• B3 (niacin: NAD)
• B5 (pantothenic acid: CoA)
• B6 (pyridoxine: PLP)
• B12 (cobalamin)
• C (ascorbic acid)
• biotin
• folate
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B5/ Pantothenic acid


• B5 (Pantothenic acid) is precursor for Co-enzyme A
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B5/ Pantothenic acid


• fatty acid synthase (fatty acid metabolism)
• pyruvate dehydrogenase (TLCFN)
• α-ketoglutarate dehydrogenase (TLCFN)

• Deficiency is very rare


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Water-soluble Vitamins
• B1 (thiamine: TPP)
• B2 (riboflavin: FAD and FMN)
• B3 (niacin: NAD)
• B5 (pantothenic acid: CoA)
• B6 (pyridoxine: PLP)
• B12 (cobalamin)
• C (ascorbic acid)
• biotin
• folate
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B6/ Pyridoxal phosphate


• Three forms:
• Pyridoxine (plants)
• Pyridoxal, pyridoxamine (animals)
• All converted to pyridoxal phosphate (PLP)
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B6/ Pyridoxal phosphate


• Co-factor in many different reactions
1. Amino acids metabolism
2. Required for heme synthesis
B6/ Pyridoxal phosphate deficiency
• B6 is needed for synthesis of γ-
aminolevulinic acid (ALA)
• ALA is a key precursor in the
biosynthesis of heme
• Deficiency can result in
sideroblastic anemia
• Iron cannot be incorporated into
heme
• Iron accumulates in RBC
cytoplasm

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B6/ Pyridoxal phosphate & Isoniazid


• Isoniazid (INH) is a tuberculosis drug
• Similar to B6 structure
• Forms inactive pyridoxal phosphate
• Result in B6 deficiency
• Must supplement B6 when taking INH
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Water-soluble Vitamins
• B1 (thiamine: TPP)
• B2 (riboflavin: FAD and FMN)
• B3 (niacin: NAD)
• B5 (pantothenic acid: CoA)
• B6 (pyridoxine: PLP)
• B12 (cobalamin)
• C (ascorbic acid)
• biotin
• folate
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B12/ Cobalamin
• used in synthesis of thymidine (DNA)
• used in metabolism of homocysteine ( methionine
metabolism)
• Deficiency of B12: ↓ DNA synthesis (megaloblastic
anemia)
B12/ Cobalamin deficiency
• Megaloblastic anemia
(macrocytic : ↑MCV)
• found also in folate
deficiencies
• hypersegmented
neutrophils
• neurologic symptoms
(parethesias) due to
Causes:
Gastric bypass surgery abnormal myelin
less intrinsic factor produced
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Water-soluble Vitamins
• B1 (thiamine: TPP)
• B2 (riboflavin: FAD and FMN)
• B3 (niacin: NAD)
• B5 (pantothenic acid: CoA)
• B6 (pyridoxine: PLP)
• B12 (cobalamin)
• C (ascorbic acid)
• biotin
• folate
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C/ Ascorbic Acid
1. Is an antioxidant, ↓ oxidation of LDL
2. keeps iron in Fe2+ reduced state, ↑
intestinal absorption
3. Required for collagen synthesis
• essential for hydroxylation of proline and lysine
• Cofactor for prolyl and lysyl hydroxylases
• addition of hydroxyl group allows for hydrogen
bonding between fibers
• without cross-linking triple helix shape cannot
form
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C/ Ascorbic Acid
• found in fruits and vegetables
• British sailors carried limes to prevent scurvy
• Deficiency caused by diet lacking citrus fruits and
green vegetables, cigarette smoking
• Seen with “tea and toast” diet (no fruits/vegetables)
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C/ Ascorbic Acid deficiency


• fragile blood vessels
• swollen bleeding gums
• perifollicular hemorrhage
• poor wound healing
• easy bruising (ecchymosis)
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Water-soluble Vitamins
• B1 (thiamine: TPP)
• B2 (riboflavin: FAD and FMN)
• B3 (niacin: NAD)
• B5 (pantothenic acid: CoA)
• B6 (pyridoxine: PLP)
• B12 (cobalamin)
• C (ascorbic acid)
• biotin
• folate
Biotin

 Involved in ATP dependent carboxylation reactions: pyruvate


carboxylase
 Produced by gut microflora
 Deficiencies are rare
 Consuming 6 raw eggs a day can cause deficiencies due to
the presence avidin (biotin binding protein)
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Water-soluble Vitamins
• B1 (thiamine: TPP)
• B2 (riboflavin: FAD and FMN)
• B3 (niacin: NAD)
• B5 (pantothenic acid: CoA)
• B6 (pyridoxine: PLP)
• B12 (cobalamin)
• C (ascorbic acid)
• biotin
• folate
B9/ Folic acid

PABA glutamate

pterin

• Folic acid converted to tetrahydrofolate (THF),


a coenzyme for 1-carbon transfer/methylation
reactions
• important for the synthesis of nitrogenous
bases in DNA and RNA
B9/ Folic acid deficiency

• Important during pregnancy


to prevent neural tube
defects in fetus ( spina bifida)
• Vitamin B12 deficiencies
cause folate deficiencies

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