Biochemistry

Vitamins
What do Vitamins actually do?

- they are co-factors or co-enzymes

- they help proteins perform various
functions within the body.

e.g. - enzymes in energy metabolism

- vision (Vit. A)
 The B Vitamins
• Coenzymes
 Vitamins
"vita" = Latin word for life.
A group of organic nutrients required in small
quantities for a variety of biochemical
functions and which , generally , cannot be
synthesized by body and must therefore be
supplied in the diet.
• Some vitamins are measured in I.U.s
(International Units), which is a
measure of biological activity.
• This measuring system is needed
because these vitamins have several
natural forms that have different
activities on an equal weight basis.
• Other vitamins are measured on the
basis of weight (mg or μg).
5
• In the United States, the Food and
Drug Administration (FDA) sets
“Daily Reference Intakes,” (DRI)
which are the highest amounts of
daily vitamins that are needed by
95% of the population.

6
 What does RDA mean?
• Recommended Dietary Allowances
• These are suggested levels of essential
nutrients considered adequate to meet
nutritional needs of healthy individuals.
Vitamin Structure and Function
• All vitamins contain carbon, hydrogen,
and oxygen
– Some vitamins contain nitrogen and
sulfur
• Chemical structure of each vitamin is
unique
• Each vitamin is a singular unit
• Vitamins are absorbed intact
• Vitamins perform numerous essential
functions
The Vitamins
Digesting and Absorbing Vitamins
Digesting and Absorbing Water-Soluble Vitamins
 VITAMIN B1
• Vitamin B1 (thiamine) the name
implies sulfur and amine in the
molecule
–Water soluble
–Found in polishings of yeast and rice
(about 5-10 grams from 1 ton of rice)
 VITAMIN B1
• Thiamine (or a thiazolium salt)
R
H3C N NH2
S O

N
N
+
Cl-
CH3

Thiamine
R = mon, di or triphosphate
VITAMIN B1
• 1998 RDA
– men: 1.2 mg/day
– women: 1.1 mg/day

• Chief functions in the body

– Part of coenzyme TPP (thiamin
pyrophosphate) used in energy metabolism
 +
N CH2 N CH3 O O
H3C NH2 HC CH2 CH2 O P O P OH
N S
OH OH

Thiamine pyrophosphate (TPP)

Thiamin (TPP) - Vit B1 involved in the
conversion of pyruvate to acetyl-CoA
pyruvate dehydrogenase complex

O
O
O-
H3 C CoA + CO2
H3C S
O

pyruvate acetyl CoA

 NH2 H
NH2 H
+ N N+ S
N N S
H3 C N
H3C N

thiamine pyrophosphate TPP O

HO O
P O O
thiamine (B1) -
O P O-
-
O

H3C OH
NH2 CH
O
N N+ S CO2
- +
O
H3C H3C N
O

first step in pyruvate dehydrogenase complex O O

P O O
-
O P O-
-
O
©2001 Brooks/Cole, a division of Thomson Learning, Inc. Thomson Learning™ is a trademark used herein under license.

Thiamin

Pork is the
richest source
of thiamin, but
enriched or
whole-grain
products
typically make
the greatest
contribution to
a day’s intake
because of the
quantities
eaten.
Copyright 2005 Wadsworth Group, a division of Thomson Learning
 VITAMIN B1
• Deficiency disease
– Beriberi
• Wet, with edema
• Dry, with muscle wasting
• Deficiency symptoms
– Enlarged heart, cardiac failure
– Muscular weakness
– Apathy, poor short-term memory, confusion,
irritability
– Anorexia, weight loss
© 2008 Thomson - Wadsworth
Rubin and Farber, Pathology - 2nd edition,
 Riboflavin
• Other names: Vitamin B2
• 1998 RDA
– Men: 1.3 mg/day
– Women: 1.1 mg/day
• Chief functions in the body
– Part of coenzymes FMN (flavin
mononucleotide) and FAD (flavin
adenine dinucleotide) used in energy
metabolism.
Riboflavin
Sources
Copyright 2005 Wadsworth Group, a division of Thomson Learning
Riboflavin

Copyright 2005 Wadsworth Group, a division of Thomson Learning

 O
H3C N H H
N O
H3C N H
N
H3C N N O
O
CH2 N H H3C N N O
H3C
N
OH H
H3C N N O
OH FADH2
OH CH2

OH
OH
OH
riboflavin (B2) OH
O NH2
O
O P N
-
O O P N
- O
O
N N
O

HO OH

Flavin adenine dinucleotide FAD

 NH2
N

O O N
H2C O P O P O CH 3 N
O
HCOH OH OH
HCOH
HCOH
CH 3 OH OH

H3C N N
O
C
Ⅲ Ⅱ Ⅰ
NH
H3C N C
O

Vit B2
FMN AMP
FAD
Riboflavin
Deficiency disease: ariboflavinosis

Signs and symptoms of deficiency

Sore throat, glossitis, cheilosis (red lips)
Anemia, neuropathy

Toxicities, contraindications and other notes

Only known use in treating deficiency
Excess intake can cause yellow urine
Excess can interfere with B1 & B6
Rubin and Farber, Pathology - 2nd edition,
• Other names
Niacin
– Nicotinic acid
– Nicotinamide
– Niacinamide
– Vitamin B3
• Precursor: dietary tryptophan
• 1998 RDA
– Men: 16 mg NE/day
– Women: 14 mg NE/day
• Upper level for adults: 35 mg/day
 Niacin
• Chief functions in the body
– Part of coenzymes NAD (nicotinamide
adenine dinucleotide) and NADP (its
phosphate form) used in energy metabolism
• Significant sources
– Milk, eggs, meat, poultry, fish
– Whole-grain and enriched breads and
cereals
– Nuts
– All protein-containing foods
Niacin
Sources
Copyright 2005 Wadsworth Group, a division of Thomson Learning
 H H O
O
- NH2
O

N
N+
H
H O NADH
niacin (B3)
NH2

N+ H- = H+ + 2e-

O O
O
O P O- NH2
OH
NH2 N
O OH N

N+ O
N N
P O O
H
-
O
nicotinamide
HO OH
nicotinamide adenine dinucleotide NAD+
Mechanism of niacin action: Niacin inhibits the
release of free fatty acids from adipose tissue, which
leads to decreased VLDL secretion by the liver.
 Niacin
• Deficiency disease: pellagra
• Deficiency symptoms
– Diarrhea, abdominal pain, vomiting
– Inflamed, swollen, smooth, bright red
tongue
– Depression, apathy, fatigue, loss of
memory, headache…similar to raising
some children, or attending college!
Rubin and Farber, Pathology - 2nd edition,
Bilateral
symmetrical rash
(sunlight
exposure) of
pellagra
can be disturbing!
 Niacin
• Toxicity symptoms
– Painful flush, hives, and rash (“niacin
flush”)
– Excessive sweating
– Blurred vision
– Liver damage,
– impaired glucose
tolerance
Biotin
 Biotin
• 1998 adequate intake (AI)
– Adults: 30 g/day
• Chief functions in the body
– Part of a coenzyme used in energy
metabolism, fat synthesis, amino acid
metabolism, and glycogen synthesis
• Significant sources
– Widespread in foods
– Organ meats, egg yolks, soybeans, fish, whole grains
– Also produced by GI bacteria!
 O O
CO2 O
H N N H C N N H
-
O
Enzyme Enzyme
S S

biotin
 Biotin
• Deficiency symptoms
– Depression, lethargy, hallucinations,
numb or tingling sensation in the arms
and legs
– Red, scaly rash around the eyes, nose,
and mouth
– Hair loss
Biotin
Toxicities

Chronic consumption of raw eggs can

induce deficiency.

Chronic inflammatory bowel disease can

cause deficiency.
Pantothenic Acid
• 1998 adequate intake (AI)
– Adults: 5 mg/day
• Chief functions in the body
– Part of coenzyme A, used in energy
metabolism
• Significant sources
– Widespread in foods
– Organ meats, mushrooms, avocados, broccoli,
whole grains
• Easily destroyed by food processing
 H OH
O
N CH3
OH
-
O O CH3
pantothenic acid

H OH
O
N CH3

O NH2
N O CH3
H O P O- N N
O
O P O- N N
O O
SH
acceptor site for acetyl group OH

OH
coenzyme A: CoA
 Pantothenic Acid
• Deficiency symptoms
– Vomiting, nausea, stomach cramps
– Insomnia, fatigue, depression,
irritability, restlessness, apathy
– Hypoglycemia, increased sensitivity to
insulin
Pantothenic (B5)
Toxicities:

Megadose can cause diarrhea and water

retention
 Vitamin B6
• Other names
– Pyridoxine
– Pyridoxal
– Pyridoxamine
• 1998 RDA
– Adults (19-50 years): 1.3 mg/day
• Upper level for adults: 100 mg/day
Vitamin
B6
Sources
Copyright 2005 Wadsworth Group, a division of Thomson Learning
 Vitamin B6
• Chief functions in the body
– Part of coenzymes PLP (pyridoxal
phosphate) and PMP (pyridoxamine
phosphate) used in amino acid and fatty acid
metabolism
– Helps to convert tryptophan to niacin and to
serotonin (a brain hormone)
– Helps to make red blood cells!
 vitamin B6

OH O
OH OH
OH OH
+ +
N CH3 N CH3
H H

pyridoxine pyridoxal
O
-
O O
NH2 - O
OH O
OH
OH
+
+
N CH3
N CH3
H
H
pyridoxal phosphate
pyridoxamine
 vitamin B6 - catalyzed reactions
R
O R O
O H N O
-
O O H O- -
O N O-
-
O O - O H
O
OH O
+ +
N CH3 N CH3
H H
pyridoxal phosphate Schiff base

Transamination: oxaloacetate + glutamate --> aspartate + alpha ketoglutarate

Deamination: serine --> pyruvate

Decarboxylation: histidine --> histamine

Condensation: glycine + succinyl CoA --> gamma-aminolevulinic acid

 Vitamin B6
• Significant sources
– Meats, fish, poultry
– Potatoes, legumes, non-citrus fruits
– Fortified cereals
– Liver
– Soy products
• Deficiency symptoms
– Scaly dermatitis
– Anemia (small-cell type)
– Depression, confusion, abnormal brain wave
pattern, convulsions
 Vitamin B6
• Toxicity symptoms
– Depression, fatigue, irritability, headaches

– Nerve damage causing numbness and muscle

weakness leading to an inability to walk and
convulsions

– Skin lesions
 Folate
• Other names
– Folic acid
– Folacin
– Pteroylglutamic acid (PGA)
• 1998 RDA
– Adults: 400 g/day
• Upper level for adults: 1000 g/day
 Folate
• Recommendations
– Dietary folate equivalents (DFE)

– Synthetic is 1.7 fold more powerful

than the natural!

• Also, folate activation needs vitamin B12

 Folate
• Chief functions in the body
– Part of coenzymes THF
(tetrahydrofolate) and DHF
(dihydrofolate) used in DNA synthesis
and therefore important in new cell
formation
• Significant sources
– Fortified grains
– Leafy green vegetables, legumes, seeds
– Liver
 Folate
Sources
 Folate
• Deficiency symptoms
– Anemia (large-cell type)
– Smooth, red tongue
– Mental confusion, weakness, fatigue,
irritability, headache
• Toxicity symptoms
– Masks vitamin B12-deficiency symptoms
Rubin E, Pathology, p1379
 Vitamin B12
• Other names: cobalamin (and
related forms)
• 1998 RDA
– Adults: 2.4 g/day
• Chief functions in the body
– Part of coenzymes methylcobalamin
and deoxyadenosylcobalamin used in
new cell synthesis
– Helps to maintain nerve cells
– Reforms folate coenzyme
– Helps to break down some fatty
acids and amino acids
Champe and Harvey, p. 327
 Vitamin B12
• Deficiency of folate or B12 produces
pernicious anemia
Vitamin C
Sources
Copyright 2005 Wadsworth Group, a division of Thomson Learning
Vitamin C
 Vitamin C
• Other name: ascorbic acid
• 2000 RDA
– Men: 90 mg/day
– Women: 75 mg/day
– Smokers: + 35 mg/day
• Upper level for adults: 2000
mg/day
 Vitamin C
• Chief functions in the body
– Collagen synthesis
• Strengthens blood vessel walls, forms scar tissue,
provides matrix for bone growth
– Antioxidant
– Thyroxin synthesis-helps prevent goiter
– Amino acid metabolism
– Strengthens resistance to infection
– Helps in absorption of iron
 Vitamin C and collagen synthesis

O OH
O
OH
HO OH

vitamin C: ascorbic acid

sugar attachment site
OH

H H H H
N N N N N
N

O O O O

proline hydroxyproline
 Vitamin C and hydroxyl radical formation

superoxide dismutase
- +
2 O2 + 2 H H2O2 + O2
superoxide hydrogen peroxide

catalase
2 H2O2 2 H2O + O2

H2O2 + Fe2+
Fenton reaction

Fe3+ + HO  + HO
-


ascorbic acid

HO DNA damage
lipid peroxidation
 Vitamin C
• Deficiency disease: scurvy
• Deficiency symptoms
– Anemia (small-cell type)
– Atherosclerotic plaques
– Pinpoint hemorrhages, bone fragility, joint
pain
– Poor wound healing, frequent infections,
bleeding gums, loosened teeth
– Muscle degeneration and pain, hysteria,
depression, rough skin, blotchy bruises
Rubin and Farber, Pathology - 2nd edition, p. 333
© 2008 Thomson - Wadsworth
 Vitamin C
• Toxicity symptoms
– Nausea, abdominal cramps, diarrhea
– Headache, fatigue, insomnia
– Hot flashes, rashes
– Interference with medical tests, aggravation
of gout symptoms, urinary tract problems,
kidney stones