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VITAMINS
HARSHIT SHETH
Nutrients
Carbohydrates
Fats
Proteins
Vitamins
Minerals
Water
Vitamins
 The word "vitamin" comes from vita, the
Latin for "life“
 Everybody must eat a certain amount of
vitamins to stay healthy
 Vitamins are chemicals found in very
small amounts in many different foods.
Tiny quantities are enough for the needs
of the body
 If people live on a very limited range of
foods they may not get their proper share
of vitamins
Classification of
Vitamins Vitamins, of which there
are 14, are classified
into two main groups:
Water soluble and Fat
soluble
 Fat soluble – stored in
bodies fat tissue
 A, D, E & K
 Water soluble – not
stored in the body
 B vitamins, folic acid &
vitamin C
CLASSIFICATION
OF VITAMINS:
Vitamin B7
Vitamin B5
Vitamin C - Ascorbic
Acid
 Structure
 Metabolism
 oxidation/reduction
 dehydroascorbic acid
 dehydroascorbate
reductase
 glutathione (GSH)
 glutamate-cysteine-
glycine
Vitamin-C(Ascorbic acid)
 Vitamin C - helps to
maintain skin integrity,
absorb iron from the gut
and heal wounds, and is
important in immune
functions
Dietary sources:
 Vitamin C is found in citrus
fruit and juices, tomatoes,
spinach, potatoes, berries,
green and red peppers,
and broccoli
Functions of
Vitamin C
Enhances absorption of
iron
reduces iron to more
absorbable ferrous form
chelates with ferrous ion to
make it more soluble
Functions of
Vitamin C
Hydroxylation of proline and
lysine
post-translational reaction of
procollagen
hydroxylated collagen can be cross-
linked to triple helix collagen
Scurvy - weak collagen
Functions of
Vitamin C
Hydroxylation Reactions
Involves O2 and metal coenzyme
 (ferrous, cuprous)
Carnitine synthesis
Tyrosine synthesis & catabolism
Functions of
Vitamin C
Hydroxylation Reactions
Synthesis of Neurotransmitters
Dopamine
Norepinephrine
Serotonin
Bile acid synthesis
Functions of
Vitamin C
Antioxidant Activity
Reacts and removes active
oxygen species
Pro-oxidant Activity
Reduces metals to their pro-
oxidant forms
Scurvy
Bleeding gums
petechiae
easy bruising
impaired wound healing and
bone repair
joint pain
anemia
RDA for Vitamin C
10 mg/day prevents scurvy
historic RDA’s 45-70 mg (60mg
in 1989), 75mg in 2000
prevention of scurvy vs
antioxidant effect with
supplements?
Toxicity of Vitamin C
 UL adults: 2000mg/d
 Osmotic diarrhea
 Oxalate kidney stones
 Decreases uric acid reabsorption
resulting in increased risk of gout
 Affects diagnostic tests in feces and
gout
 fecal blood
 urinary glucose
VITAMIN B-COMPLEX
Thiamin- B1
Structure
pyrimidine ring
thiazole ring
methyl bridge
Thiamin : vitamin form
Thiamin pyrophosphate: coenzyme form
Pyrimidine ring Thiazole ring
Dietary sources: cereals, pulses, oil
seeds, nuts and yeast are goods
sources.
 In animal food like pork, liver, heart,
kidney, milk etc.
 RECOMMENDED DIETARY
ALLOWANCE: Adults: 1-1.5 mg/day.
Children: 0.7-1.2 mg/day.
Biochemical
Functions of B-1
 Oxidative Decarboxyation Reactions
 Pyruvate Dehydrogenase
 Pyr+CoA+NAD --> AcCoA+CO2 +NADH
 a-keto-glutarate dehydrogenase
 aKG+CoA+NAD-->SuccCoA + CO2+NADH
 important in CHO/energy metabolism
Biochemical
Functions of B-1
Transketolation
HMP pathway
Peripheral Nerve Function
TPP or TPPP
non-cofactor function
mechanism?
Thiamin
Deficiency
Beri-Beri
anorexia, fatigue, depression
effects on
cardiovascular system
nervous system
Infantile Beri-Beri
first 6 months
breast milk deficient in B-1
mother w/o symptoms
rapid onset
cyanosis, tachycardia, labored
breathing
heart failure and death
Wet Beri Beri
 symptoms similar to congestive
heart failure
 Pitting edema - trunk, limbs, face
 labored breathing, tachycardia
 rapid deterioration
 fatal cirulatory collapse
 responds rapidly to B-1
supplements
Dry Beri-Beri
no edema
progressive wasting
numbing and
weakening of
extremities
chronic infections
Assessment of
Thiamin Status
Urinary thiamin excretion
Blood or serum thiamin
concentration
[pyr + lac] in blood
erythrocyte transketolase
activity
stimulation with B-1
RIBOFLAVIN-B2
 Structure: 6,7 dimethyl isoalloxazine +
D-ribitol. Attached by nitrogen atom.
Niacin
Structure
Nicotinic Acid = Niacin
Nicotinamide =
Niacinamide
Cofactor Forms of
Niacin
 Nicotinamide Adenine Dinucleotide
 NAD
 nicotinamide-ribose-PP-ribose-adenine
 Nicotinamide Adenine Dinucleotide
Phosphate
 NADP
 nicotinamide-ribose-PP-(ribose-P)-adenine
Nicotinic Acid (Plant form)
Nicotinamide (animal form)
(reduced form)
Nicotinamide Adenine Dinucleotide
nicotinamide
adenine
If Phosphate here ->
NADP
Biochemical
Functions of B-3
Oxidation-Reduction
Reactions (NAD/NADH
 Dehydrogenases
 Electron Transport System
 Involved in energy production
Biochemical
Functions of B-3
Synthetic Pathways (NADPH)
 FA synthesis
 Cholesterol synthesis
 NEAA synthesis
 Purine & Pyrimidine synthesis
Deficiency of B-3
Pellegra
Dermatitis
 scaly dermatitis, sun exposed
Dementia
 confused, disoriented
Diarrhea
 irritation/inflammation of mucous membranes
Assessment of B-3
Status
Urinary excretion of niacin
metabolites
N-methyl nicotinamide
2-pyridone
Vitamin B-12
Structure
cobalamine
methyl
cobalamine
 transport and
coenzyme form
adenosyl
cobalamine
 storage and
coenzyme form
Dietary Sources
Animal products
 including milk and eggs
GI microorganisms
Vegan sources
 N-fixing legumes
 fortified grains
 vitamin supplements
Digestion &
Absorption of B12
Intrinsic Factor
 gastric glycoprotein
 binds with B12 in small intestine
 IF-B12 complex binds to B12receptor in
ileum for absorption
 B12 absorption requires functioning
stomach, pancreas, and ileum
Causes of B-12
Deficiency
Inadequate intake - rare
DRI adults 2.4 ug/d
Usual intake 7-30 ug/d
Malabsorption of B-12
IF deficiency
other GI tract problems
Functions of B12
Homocysteine to Methionine
 methionine synthetase
requires 5-methyl THF
deficiency of B12 results in “methyl-
trap” of folate
 results in megaloblastic anemia
 synergistic effect of B12 and folate
Functions of B12
Mutases
methyl malonyl CoA mutase
proprionyl-CoA ->->succinyl-CoA
accumulation of methyl-malonate
may inhibit AcetylCoA carboxylase
B-12 Deficiency
 Pernicious anemia
 megaloblastic anemia
 Methyl-folate trap
 Delayed or failure of normal cell division
due to impaired DNA synthesis
 neuropathy
 defective myelination
 progressive peripheral weakening
 unresponsive to folate
 upper limit to folate
supplementation/enrichment
Folic Acid / Folacin
Structure
 pteridine ring - PABA - glutamate
Stability
very sensitive to heat
easily oxidized
leached
RDA : 200 microgram/day.
During pregnance:400 microgram/day
Folate Functions
Single carbon metabolism
Folate
Functions
 Interconversion of serine and glycine
 ser + THF <---> gly + 5,10-Me-THF
 Degradation of histidine
 his->->->formiminoglutamate(FIGLU)
 FIGLU+THF -> glu + 5-forminino-THF
 histidine load test
 Functional test for folate status
Folate Functions
Purine and Pyrimidine
Synthesis
 dUMP + 5,10-Me-THF -> dTMP + THF
Methionine Synthesis
 homocysteine + 5-Me-THF -> MET +
THF
 MET as a methyl donor for choline
synthesis
Folate Deficiency
Megaloblastic Anemia
 decreased DNA synthesis
 failure of bone marrow cells to divide
 normal protein synthesis
 results in large immature RBC’s
 contrast with microcytic hypochromic
anemia
Folate Deficiency
Homocysteine
 Coronary Heart Disease risk factor ?
 genetic homocystinuria - premature
CHD
 hi [homocys] related to hi CHD risk
 lo [folate, B-12, B-6] related to hi CHD
risk
 lo intake of B-vit related to hi CHD risk
Folate and CHD
Nurse’s Health Study (JAMA 1998)
80,000 nurses, 14 yr follow-up
Relative Risk - highest vs lowest
quintile
RR = 0.69 for folate
RR = 0.67 for B-6
RR = 0.55 for folate + B-6
Folate and Neural
Tube Defects
Defects in formation of neural
tube (brain & spinal cord)
First two months gestation
Anencephaly
absence of cerebral hemispheres
Folate and Neural
Tube Defects
Spina bifida
 defective closure of vertebral column
 spinal cord protrusion from spinal
column results in damage to spinal
cord
 lower limb and hip paralysis
 rectal and bladder problems
Names and Roles
Vitamins
A retinol phototransduction
D cholecalciferol bone remodeling
E tocopherols antioxidant
K phytylmenaquinone
multiprenylmenaquinone
coagulation
bone remodeling
B1 thiamine carbohydrate metabolism
B2 riboflavin redox, respiration
B3
niacin redox
B6
pyridoxine
pyridoxamine
pyridoxal
aa metabolism
glycogenolysis
B5 Pantothenic acid tca, fa and cholesterol
B7 Biotin gluconeogenesis, tca, fa, aa
B12 cobalamin 1C&H metabolism
B9 Folic acid 1C metabolism
C ascorbic acid hydroxylation
Deficiencies and Sources
Vitamins
A - night blindness
preformed: liver, egg yolk, butter, milk
β-carotene: dark green and yellow veggies
D - ricketts, osteomalacia milk, fortified food, fish oils, egg
yolks, liver
E - neurologic?, hemolytic anemia veggie oils, nuts
K - bleeding disorders green leafy veggies, fruits, dairy products, veggie
oils, cereals, meats
B1 - beri-beri seeds, nuts, wheatgerms, legumes, lean meat
B2 - pellagra meats, nuts, legumes
B3 - pellagra meats, nuts, legumes
B6 - neurologic disease yeast, liver, wheatgerm, nuts, beans,
bananas
B7 - widespread injury corn, soy, egg yolk, liver, kidney,
tomatoes
B12 - pernicious anemia liver, kidney, egg, cheese
B9 - anemia yeast, liver, leafy veggies
C - scurvy citrus and soft fruits
B5 - none known yeast, grains, egg yolk, liver
 THANKS

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Vitamins

  • 3. Vitamins  The word "vitamin" comes from vita, the Latin for "life“  Everybody must eat a certain amount of vitamins to stay healthy  Vitamins are chemicals found in very small amounts in many different foods. Tiny quantities are enough for the needs of the body  If people live on a very limited range of foods they may not get their proper share of vitamins
  • 4. Classification of Vitamins Vitamins, of which there are 14, are classified into two main groups: Water soluble and Fat soluble  Fat soluble – stored in bodies fat tissue  A, D, E & K  Water soluble – not stored in the body  B vitamins, folic acid & vitamin C
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  • 10. Vitamin C - Ascorbic Acid  Structure  Metabolism  oxidation/reduction  dehydroascorbic acid  dehydroascorbate reductase  glutathione (GSH)  glutamate-cysteine- glycine
  • 11. Vitamin-C(Ascorbic acid)  Vitamin C - helps to maintain skin integrity, absorb iron from the gut and heal wounds, and is important in immune functions Dietary sources:  Vitamin C is found in citrus fruit and juices, tomatoes, spinach, potatoes, berries, green and red peppers, and broccoli
  • 12. Functions of Vitamin C Enhances absorption of iron reduces iron to more absorbable ferrous form chelates with ferrous ion to make it more soluble
  • 13. Functions of Vitamin C Hydroxylation of proline and lysine post-translational reaction of procollagen hydroxylated collagen can be cross- linked to triple helix collagen Scurvy - weak collagen
  • 14. Functions of Vitamin C Hydroxylation Reactions Involves O2 and metal coenzyme  (ferrous, cuprous) Carnitine synthesis Tyrosine synthesis & catabolism
  • 15. Functions of Vitamin C Hydroxylation Reactions Synthesis of Neurotransmitters Dopamine Norepinephrine Serotonin Bile acid synthesis
  • 16. Functions of Vitamin C Antioxidant Activity Reacts and removes active oxygen species Pro-oxidant Activity Reduces metals to their pro- oxidant forms
  • 17. Scurvy Bleeding gums petechiae easy bruising impaired wound healing and bone repair joint pain anemia
  • 18. RDA for Vitamin C 10 mg/day prevents scurvy historic RDA’s 45-70 mg (60mg in 1989), 75mg in 2000 prevention of scurvy vs antioxidant effect with supplements?
  • 19. Toxicity of Vitamin C  UL adults: 2000mg/d  Osmotic diarrhea  Oxalate kidney stones  Decreases uric acid reabsorption resulting in increased risk of gout  Affects diagnostic tests in feces and gout  fecal blood  urinary glucose
  • 22. Thiamin : vitamin form Thiamin pyrophosphate: coenzyme form Pyrimidine ring Thiazole ring
  • 23. Dietary sources: cereals, pulses, oil seeds, nuts and yeast are goods sources.  In animal food like pork, liver, heart, kidney, milk etc.  RECOMMENDED DIETARY ALLOWANCE: Adults: 1-1.5 mg/day. Children: 0.7-1.2 mg/day.
  • 24. Biochemical Functions of B-1  Oxidative Decarboxyation Reactions  Pyruvate Dehydrogenase  Pyr+CoA+NAD --> AcCoA+CO2 +NADH  a-keto-glutarate dehydrogenase  aKG+CoA+NAD-->SuccCoA + CO2+NADH  important in CHO/energy metabolism
  • 25. Biochemical Functions of B-1 Transketolation HMP pathway Peripheral Nerve Function TPP or TPPP non-cofactor function mechanism?
  • 27. Infantile Beri-Beri first 6 months breast milk deficient in B-1 mother w/o symptoms rapid onset cyanosis, tachycardia, labored breathing heart failure and death
  • 28. Wet Beri Beri  symptoms similar to congestive heart failure  Pitting edema - trunk, limbs, face  labored breathing, tachycardia  rapid deterioration  fatal cirulatory collapse  responds rapidly to B-1 supplements
  • 29. Dry Beri-Beri no edema progressive wasting numbing and weakening of extremities chronic infections
  • 30.
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  • 32. Assessment of Thiamin Status Urinary thiamin excretion Blood or serum thiamin concentration [pyr + lac] in blood erythrocyte transketolase activity stimulation with B-1
  • 33. RIBOFLAVIN-B2  Structure: 6,7 dimethyl isoalloxazine + D-ribitol. Attached by nitrogen atom.
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  • 38. Niacin Structure Nicotinic Acid = Niacin Nicotinamide = Niacinamide
  • 39. Cofactor Forms of Niacin  Nicotinamide Adenine Dinucleotide  NAD  nicotinamide-ribose-PP-ribose-adenine  Nicotinamide Adenine Dinucleotide Phosphate  NADP  nicotinamide-ribose-PP-(ribose-P)-adenine
  • 40. Nicotinic Acid (Plant form) Nicotinamide (animal form) (reduced form)
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  • 44. Biochemical Functions of B-3 Oxidation-Reduction Reactions (NAD/NADH  Dehydrogenases  Electron Transport System  Involved in energy production
  • 45. Biochemical Functions of B-3 Synthetic Pathways (NADPH)  FA synthesis  Cholesterol synthesis  NEAA synthesis  Purine & Pyrimidine synthesis
  • 46. Deficiency of B-3 Pellegra Dermatitis  scaly dermatitis, sun exposed Dementia  confused, disoriented Diarrhea  irritation/inflammation of mucous membranes
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  • 49. Assessment of B-3 Status Urinary excretion of niacin metabolites N-methyl nicotinamide 2-pyridone
  • 50. Vitamin B-12 Structure cobalamine methyl cobalamine  transport and coenzyme form adenosyl cobalamine  storage and coenzyme form
  • 51. Dietary Sources Animal products  including milk and eggs GI microorganisms Vegan sources  N-fixing legumes  fortified grains  vitamin supplements
  • 52. Digestion & Absorption of B12 Intrinsic Factor  gastric glycoprotein  binds with B12 in small intestine  IF-B12 complex binds to B12receptor in ileum for absorption  B12 absorption requires functioning stomach, pancreas, and ileum
  • 53. Causes of B-12 Deficiency Inadequate intake - rare DRI adults 2.4 ug/d Usual intake 7-30 ug/d Malabsorption of B-12 IF deficiency other GI tract problems
  • 54. Functions of B12 Homocysteine to Methionine  methionine synthetase requires 5-methyl THF deficiency of B12 results in “methyl- trap” of folate  results in megaloblastic anemia  synergistic effect of B12 and folate
  • 55. Functions of B12 Mutases methyl malonyl CoA mutase proprionyl-CoA ->->succinyl-CoA accumulation of methyl-malonate may inhibit AcetylCoA carboxylase
  • 56. B-12 Deficiency  Pernicious anemia  megaloblastic anemia  Methyl-folate trap  Delayed or failure of normal cell division due to impaired DNA synthesis  neuropathy  defective myelination  progressive peripheral weakening  unresponsive to folate  upper limit to folate supplementation/enrichment
  • 57. Folic Acid / Folacin Structure  pteridine ring - PABA - glutamate Stability very sensitive to heat easily oxidized leached
  • 58. RDA : 200 microgram/day. During pregnance:400 microgram/day
  • 60. Folate Functions  Interconversion of serine and glycine  ser + THF <---> gly + 5,10-Me-THF  Degradation of histidine  his->->->formiminoglutamate(FIGLU)  FIGLU+THF -> glu + 5-forminino-THF  histidine load test  Functional test for folate status
  • 61. Folate Functions Purine and Pyrimidine Synthesis  dUMP + 5,10-Me-THF -> dTMP + THF Methionine Synthesis  homocysteine + 5-Me-THF -> MET + THF  MET as a methyl donor for choline synthesis
  • 62. Folate Deficiency Megaloblastic Anemia  decreased DNA synthesis  failure of bone marrow cells to divide  normal protein synthesis  results in large immature RBC’s  contrast with microcytic hypochromic anemia
  • 63. Folate Deficiency Homocysteine  Coronary Heart Disease risk factor ?  genetic homocystinuria - premature CHD  hi [homocys] related to hi CHD risk  lo [folate, B-12, B-6] related to hi CHD risk  lo intake of B-vit related to hi CHD risk
  • 64. Folate and CHD Nurse’s Health Study (JAMA 1998) 80,000 nurses, 14 yr follow-up Relative Risk - highest vs lowest quintile RR = 0.69 for folate RR = 0.67 for B-6 RR = 0.55 for folate + B-6
  • 65. Folate and Neural Tube Defects Defects in formation of neural tube (brain & spinal cord) First two months gestation Anencephaly absence of cerebral hemispheres
  • 66. Folate and Neural Tube Defects Spina bifida  defective closure of vertebral column  spinal cord protrusion from spinal column results in damage to spinal cord  lower limb and hip paralysis  rectal and bladder problems
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  • 80. Names and Roles Vitamins A retinol phototransduction D cholecalciferol bone remodeling E tocopherols antioxidant K phytylmenaquinone multiprenylmenaquinone coagulation bone remodeling B1 thiamine carbohydrate metabolism B2 riboflavin redox, respiration B3 niacin redox B6 pyridoxine pyridoxamine pyridoxal aa metabolism glycogenolysis B5 Pantothenic acid tca, fa and cholesterol B7 Biotin gluconeogenesis, tca, fa, aa B12 cobalamin 1C&H metabolism B9 Folic acid 1C metabolism C ascorbic acid hydroxylation
  • 81. Deficiencies and Sources Vitamins A - night blindness preformed: liver, egg yolk, butter, milk β-carotene: dark green and yellow veggies D - ricketts, osteomalacia milk, fortified food, fish oils, egg yolks, liver E - neurologic?, hemolytic anemia veggie oils, nuts K - bleeding disorders green leafy veggies, fruits, dairy products, veggie oils, cereals, meats B1 - beri-beri seeds, nuts, wheatgerms, legumes, lean meat B2 - pellagra meats, nuts, legumes B3 - pellagra meats, nuts, legumes B6 - neurologic disease yeast, liver, wheatgerm, nuts, beans, bananas B7 - widespread injury corn, soy, egg yolk, liver, kidney, tomatoes B12 - pernicious anemia liver, kidney, egg, cheese B9 - anemia yeast, liver, leafy veggies C - scurvy citrus and soft fruits B5 - none known yeast, grains, egg yolk, liver

Editor's Notes

  1. aa: amino acidtca: tricarboxylic acid cycle fa: fatty acidac: acetylcholine pl: phospholipid1C &amp; H: one-carbon and hydrogen transfer A - retinalB1 - transketolase, pyruvate dehydrogenase B2 - pyruvate dehydrogenaseB3 - pyruvate dehydrogenase B5 - part of CoAB6 - transaminases B7 - acetyl CoA carboxylase (fatty acid synthesis) and pyruvate carboxylase B9 - thymidylate synthaseB12 - methionine synthase
  2. A deficiency in B9 (folate) can mask B12 deficiency. Several months supply of B9 in the body. Two- to three-year supply of B12 in the body; pernicious = harmful or deadly B7 (biopterin) rabies appears to induce deficiency Overdose (OD) values A &amp;gt; 25,000 IU; concentrated in polar bear liver (toxic levels) B3 &amp;gt; 2.5 g; (can be made from tryptophan, amide preferred, acid is vasodilator) B6 &amp;gt; 400 mg B9 &amp;gt; 1 mg D &amp;gt; 50,000 IU E &amp;gt; 50,000 IU Clinical assays (lab tests) for A, B1, B9, B12, C, and D3