Biochemistry 1

Vũ Thanh Ngọc, PhD

Department of Applied Chemistry
School of Biotechnology
International University – VNU HCM
[email protected]

Vitamins
 Outline

 Classification

 Structure

 Function

 Properties
 What are vitamins?
• Vitamin = historically “Vital amine”
– Because first vitamin described (Thiamine) has
an amine group
– Later drops the "e"  vitamin to deemphasize
the “amine” reference
• Vitamins are chemically unrelated organic
compounds that cannot be synthesized in
adequate quantities by humans and must be
supplied by the diet
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 Vitamins are classified by solubility
• 10 water soluble vitamins
– B group: Thiamine (B1), Riboflavin (B2),
Niacin (B3), Pantothenic acid (B5), Pyridoxine
(B6), Cobalamin (B12), Biotin (B7), Folic acid
(B9)
– Lipoic acid: vitamin-like antioxidant
(function like B vitamins)
– Non-B complex: Ascorbic acid (C)
• 4 fat soluble vitamins: A, D, E, K
General Biochemistry 1 4
 Water Soluble Vitamins
• Dissolve in water
• Readily excreted by kidney in urine
• Hydrophilic compounds & water leach them from
vegetables
• Function as coenzymes & in energy metabolism
• Vitamin C, thiamin and riboflavin are especially
susceptible to heat and alkalinity
• Marginal deficiency more common
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List of Vitamins

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 Fat Soluble Vitamins
• All Terpenes (polymer of isoprene) like sterols
• Released, adsorbed and transported
(in Chylomicrons) with dietary fat
• Excreted much more slowly
• Only vitamin K has coenzyme function
• Stored in adipose tissue & liver
• Excess consumption of Vitamin A, D
 toxicity
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Water Soluble Vitamins

General Biochemistry 1 8
 Thiamine – Vitamin B1
• First water soluble vitamin to be described
• Thiamine = Thio (sulfur) containing vitamin

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 Thiamine – Vitamin B1
Thiamine = a substituted thiazole ring
joined to a substituted pyrimidine by a
methylene bridge

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 Thiamine Pyrophosphate – TPP
• Thiamine is a precursor, it is converted to
Thiamine pyrophosphate (TPP) by TPP
synthetase
• TPP is active form of Thiamine
• TPP is a coenzyme involved in
carbohydrate/energy metabolism

General Biochemistry 1 11
 TPP – active form of Thiamine
• In Pentose phosphate pathway: TPP is a
coenzyme of formation of degradation of α-ketols
by transketolase
• In Citric Acid Cycle: TPP is a coenzyme in
oxidative decarboxylation of α-keto acids

Glycolysis
12
 Thiamine Functions
• Involvement of TPP in citric acid cycle and
pentose phosphate pathway play key role
in energy metabolism of cells
• Energy metabolism produce ATP, energy
currency of living organisms
• TPP is coenzyme of Pyruvate
Dehydrogenase (PDH), an enzyme that
regulates production of acetylcholine,
a neurotransmitter
General Biochemistry 1 13
 Sources of Thiamine
• White bread, Cereal, Enriched grains,
whole grains
• Hot dogs, luncheon meat
• Thiaminase found in raw fish inactivate
Vitamin B1 in food
• Deficiency of Thiamine causes decrease
ATP level, impairs cellular functions
General Biochemistry 1 14
 Deficiency of Thiamine
• Beriberi
– use polished rice as major component of diet
– Characterized by nerve degeneration,
weaknes, enlarge heart, heart failure, etc.
• Wernicke - Korsakoff syndrome
– chronic alcoholism, dietary insufficiency,
impaired intestinal absorption
– confusion, ataxia, and a rhythmic to-and-fro
motion of the eyeballs, memory problems and
hallucinations and dementia 15
 Coenzymes that include
adenine nucleotides
• Flavin dinucleotides (FAD, FMN) – Vitamin B2
• Pyridine dinucleotides (NAD+, NADP+) –
Vitamin B3
• Coenzyme A (CoA) – Vitamin B5
• Adenine does NOT participate in reaction
• Adenine increases affinity and specificity
of the coenzyme to enzyme (H-bond,
hydrophobic & ionic bond)
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 Riboflavin – Vitamin B2
• "riboflavin" (Rbf or RBF) comes from
– A reduced sugar "ribitol"
– A yellow color ring "flavin"
(latin flavus = yellow)
• Precursor of Flavin dinucleotide coenzyme
– Riboflavin 5'-phosphate or Flavin
mononucleotide (FMN)
– Flavin Adenine Dinucleotide (FAD)
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Biosynthesis of FAD and FMN

General Biochemistry 1 18
Riboflavin – Vitamin B2
• Izoalloxazine is the core
• Ribityl and izoalloxazine
does not form glycosidic
bond
 not truly a nucleotide
• Oxidized form of
izoalloxazine absorbs
450 nm and 350 – 380
nm  bright yellow
color
• Reduced form
General Biochemistry 1  colorless 19
Flavin coenzymes exist in 3 redox states

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 Flavin coenzyme functions
• The 3 redox states allows flavin
coenzymes to participate in one-electron
and two-electron transfer reactions
• Electron carriers in
– Redox reaction
– Electron transport chain
– Beta oxidation of fatty acids
General Biochemistry 1 21
Sources of Riboflavin and Deficiency
• Sources: Enriched grains, liver, oyster, most plants
and animal foods, dairy, bread, cereal…

• Deficiency:

– Rare, in combination with other deficiency

– Caused by longterm phenobarbital use,

alcoholics, restricted calorie diet

– Ariboflavinosis: eye, throat, CNS disorder

General Biochemistry 1 22
 Niacin – Vitamin B3
• Nicotinic acid = substituted pyridine derivative
• 'niacin' derived from nicotinic acid + vitamin
• Nicotinamide is readily deaminated 
equivalent to nicotinic acid
• Avoid perception that niacin-rich food contains
nicotine, or that cigarettes contain vitamins

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 Coenzyme NAD+ and NADP+
• Active form of Niacin is NAD+ and NADP+
• Also called Pyridine dinucleotides

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 Coenzyme NAD+ and NADP+
• Nicotinamide Adenine Dinucleotide (NAD+),
reduced form - NADH
• Nicotinamide Adenine Dinucleotide Phosphate
(NADP+), reduced form - NADPH

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NAD+, NADP+ are "two electron" carriers
• Involve transfer of hydride
anion (2 electrons) to
NAD(P) or from NAD(P)H
• The C-4 position of the
pyridine ring is reactive
center
• N is electron sink to
facilitate hydride transfer
• NAD+ is electron acceptor
• NADPH is electron donor
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 NAD+ and NADP+ functions

• NAD+ and NADP+ participates in >200

redox reactions in the body
• They are involved in Electron Transport
Chain of mitochondria in respiration and
of Chloroplast in photosynthesis

General Biochemistry 1 27
 Sources of Niacin
• Quinolinate – A metabolite of tryptophan
can be converted to NAD(P)
(60 mg W = 1 mg Niacin)
• Unrefined and enriched grains, cereal, milk
• Lean meat, liver
• Deficiency of Niacin can be caused by a
corn-based diet
(corn is low in both Niacin and Tryptophan)
General Biochemistry 1 28
 Deficiency of Niacin
• Pellagra:
– Involve skin, gastrointestinal tract,
Central nervous system
– Symptoms: Dermatitis, Diarrhea,
Dementia, death
• Hartnup disorder:
– Caused by defective absorption of Tryptophan
– Has Pellagra like symptoms
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Niacin as hyperlipidemia treatment
• Niacin at 1.5 g/day inhibits lipolysis in
adipose tissue
 reduce circulating free fatty acids
 reduce triacylglycerol synthesis
 reduce Low Density Lipoprotein
 reduce cholesterol and useful in
treatment of type IIb hyperlipoproteinemia

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 Pantothenic acid – Vitamin B5
• Name Greek pantothen = "from everywhere",
small quantities found in nearly every food
• Component of coenzyme A (CoA)

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 Pantothenic acid functions
• CoA functions in acyl transfer reactions
• The 4-phosphopantetheine group of CoA
is component of Acyl Carrier proteins
(ACPs) involved in fatty acid biosythesis
• Pantothenic acid is essential in
metabolism of fat, protein, carbohydrate
in citric acid cycles and other pathways
General Biochemistry 1 32
Sources of Vitamin B5 and Deficiency

• Sources: abundant in almost all foods

• Deficiency:
– Rare, in combination with other deficiency
– Burning foot syndrome, fatigue, headache,
sleep disturbance, nausea, abdominal distress
– Can be caused by alcoholism

General Biochemistry 1 33
 Vitamin B6
• Pyridoxal, pyridoxine, pyridoxamine
– Pyridoxal (plants), pyridoxine, pyridoxamine
(animal)
• Vitamin B6 was named pyridoxine to indicate its
structural homology to pyridine
• Not to be confused with Pyrimidine

Pyridine Pyrimidine
General Biochemistry 1 34
Coenzyme Pyridoxal-5-phosphate (PLP)
• PLP is active form of Vitamin B6
• Exists in 2 tautomeric forms
• Involved in cleavage of any bonds to Cα
and several bonds in side chains

General Biochemistry 1 35
 PLP Functions
Participates in catalysis of reactions involved
amino acids
– Transaminations
– α- and β-decarboxylation
– β- and Υ-eliminations
– Racemization
– Aldol reaction

General Biochemistry 1 36
Vitamin B6 Sources and Deficiency
• Sources: meat, fish, poultry, whole grain, banana,
spinach, avocado, potato
(Note: heat and alkaline sensitive)
• Deficiency
– Microcytic hypochromic anemia
– Seborrheic dermatitis
– Convulsion, depression, confusion
– Reduce immune response
– Peripheral nerve damage
• Risk
– Elderly
– Alcoholics
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 Cobalamin – Vitamin B12
• Generic name referring to a collection
of cobalt and corrin ring molecules
• Corrin ring (4 pyrroles) resembles porphyrin ring of
heme
• Cobalt is coordinated by 4 pyrrole Nitrogen
 Sources of Vitamin B12
• All vitamin B12 precursor must be
synthesized by microorganisms
• No fungi, plants, or animals (including
human) can produce vitamin B12 precursors
• Human merely converts B12 precursors to an
active form
• Vitamin B12 is stored primarily in the liver
• Rich in animal products: Red meat, Seafood,
Eggs, Dairy products
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Coenzyme forms of Vitamin B12

General Biochemistry 1 40
 Vitamin B12 functions
• 5 -deoxyadenosylcobalamin involved in
– Intramolecular rearrangements: isomerization of
methylmalonyl CoA during degradation of amino
acids and fatty acids
– Reductions of Ribonucleotides to
Deoxyribonucleotides (in certain bacteria)
• Methylcobalamin involved in
– Methyl group transfer (using N5-methyl-THF) to
produce methionine from homocystein
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 Vitamin B12 deficiency
Risk for Vitamin B12 deficiency
– Strict vegan diets
– Breastfed infants of vegan moms
– Elderly
– Individuals with AIDS or HIV

General Biochemistry 1 42
 Vitamin B12 deficiency
• Deficient diet takes ~20 years on a to see nerve
damage
• Pernicious anemia (autoimmune destruction intrinsic
factor IF  decreased absorption ability)
– Nerve degeneration, weakness
– Tingling/numbness in the extremities
– (parasthesia) – Paralysis and death
– Looks like folate deficiency
• Achlorhydria especially in elderly
• Treatment: Injection of B12 43
 Biotin – Vitamin H or B7
• Is a coenzyme in carboxylation reaction as
a carrier of activated CO2
• Biotin is covalently bound to ε-amino group of
lysine residues in biotin-dependent enzymes

Biocytin form

44
 Biotin Functions
• Carboxylation of acetyl-CoA to form
malonyl-CoA for the elongation of a fatty
acid chain
• Addition of CO2 to pyruvate to yield
oxaloacetate
• Breaks down leucine

General Biochemistry 1 45
 Biotin Sources and Deficiency
• Sources: Widespread in foods, Organ meats, fish,
Egg yolks, Soybeans, Whole grains
• Deficiency:
– Rare
– High intake of raw egg white diet
– Alcoholics
– Biotinidase deficiency
– Anticonvulsant drug use
– Signs & symptoms: skin rash, hair loss,
convulsion, neurological disorders, impaired
growth in children
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 Lipoic acid
• Coenzyme exists as a mixture of 2 structures:
– Closed-ring disulfide form
– Open-chain reduced form
• Often amide linked to Lysine on enzyme

General Biochemistry 1 47
 Lipoic acid functions
• Lipoic acid is an Acyl group carrier found in
– Pyruvate dehydrogenase (PDH)
– α-ketoglutarate dehydrogenase
• Lipoic acid couple acyl group transfer and
electron transfer during oxidation and
decarboxylation of α-keto acids

General Biochemistry 1 48
Sources of Lipoic acid and Deficiency
• Sources: All food, slightly more in heart, liver,
kidney, spinach, broccoli and yeast extract
• No evidence exists of a dietary lipoic acid
requirement by humans; strictly speaking, it is
not considered a vitamin!
• Nevertheless, it is an essential component of
several enzymes of intermediary metabolism
and is present in body tissues in small amounts
General Biochemistry 1 49
 Folic acid – Vitamin B9
• Sources: Green plants, fresh fruits, yeast, liver
• Name: folium, Latin for “leaf”
• Consists of pteridine group, para-
aminobenzoic acid (PABA), and glutamic acid

Folic acid - Other names: Folate, Folacin

50
 Pteridine & Pterin
Pterin from pte ́ryj - Greek for “wing” because
they were first identified in insect wings

Yellow Sulfur Butterfly & Cabbage butterfly

 Folic acid functions
• Folic acid derivatives (folates) are acceptors
and donors of "one carbon" units for all
oxidation levels of carbon exept that of CO2
• Active coenzyme form: tetrahydrofolate
(THF)
• R = (Glutamate units)1-7 bound
5
by γ-carboxyl amide bonds
5 10
10 • "One carbon units" bound at
N5, N10 or both N5 & N10

General Biochemistry 1 52
N5 – Formyl – THF N10 – Formyl – THF

53
 Folic acid functions
• Nucleotide synthesis
– Transfer of "one carbon units"
– Synthesis of purines
– Synthesis of Thymidine monophosphate (TMP)
• Amino acid synthesis: synthesize methionine
from homocystein
• Neurotransmitter synthesis: serotonin,
epinephrine, dopamine
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 Folic acid functions

Methotrexate is a folic acid analogue used to treat

cancer, psoriasis, rheutamoid arthritis, neoplasm

General Biochemistry 1 55
 Folic acid Deficiency
Nutrional anemia
• Folic acid defficiency: common in poor
diet, pregnancy, lactation, poor absorption,
alcoholism, use of Methotrexate
• Anemia = blood hemoglobin level is lower
than normal  reduced oxygen
• Nutrional anemia: abnormally big Red
blood cells (RBCs) – Macrocytic mean
corpuscular volume (MCV)
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 Megaloblastic Anemia
Folic acid or Vitamin B12 deficiency  inability of cells
to make DNA and inability to divide  accumulate
large and immature RBC precursor in bone marrow
and blood = macrocytic or megablatic anemia

General Biochemistry 1 57
 Folic acid Deficiency
Neural Tube Defects - NTDs
• Adequate folate is critical in first week of
fetal life
• Inadequate folate  Neural tube defects
• Women childbearing age should consume
0.4 mg/day to reduce risk of folic acid
deficiency during pregnancy
• Folic acid enrichment in grain products
 supplement of 0.1 mg folate/day
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 Ascorbic acid - Vitamin C
• L-Ascorbic acid - Simplest chemical
structure of all vitamins
• Ascorbic acid is strong reducing reagent
• Vitamin C, vitamin E and β-carotene
 antioxidant

General Biochemistry 1 59
 L-Ascorbic/dehyro-L-ascorbic
redox system
• L-Ascorbic is oxidized by oxygen or metal ions (Fe, Cu)
 semidehydro-L-Ascorbate (reactive free radical)
• Reducing of semidehydro-L-Ascorbate give L-
Ascorbic acid
• L-ascorbic acid is oxidized to dehydro-L-Ascorbic acid

O2, Fe, Cu

General Biochemistry 1 60
 Vitamin C functions
• Functions of vitamin C mostly derive from its
reducing properties – as an electron carrier
and antioxidant
• Coenzyme in hydroxylation of proline and
lysine in Collagen
• Stabilize reduced form of folate enzyme
• Enhance absorption of non-heme iron by
reducing ferric to ferrous (Fe3+  Fe2+)
• Helps synthesize carnitine
• Proper functioning of immune system
General Biochemistry 1 61
 Vitamin C Deficiency - Scurvy

• Most common in sailors during long ocean

voyages when food supplies are depleted
of vitamin C
• Characterized by: anemia, weak
collagenous structures: bones, cartilage,
teeth, connective tissue

General Biochemistry 1 62
 Sources of Vitamin C
• Can be synthesized by most plants and
animals
• A few vertebrates unable to synthesize:
human, other primates, guinea pigs, etc.
• Sources in food: Citrus fruits, potatoes,
green peppers, Cauliflowers, Broccoli,
strawberries, romaine lettuce, spinach
• Note: sensitive to heat, O2, Fe, Cu, easily
loss through cooking
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Fat Soluble Vitamins

General Biochemistry 1 64
 Vitamin A
• A Terpene (from isoprene)
• Retinol = Vitamin A - A primary alcohol containing a
β-ionone ring with an unsaturated side chain,
Retinyl esters (long chain fatty acids – eg.Palmitic)
• Retinal = Aldehyde form of Retinol
• Retinoic acid = Acid form of Retinal

General Biochemistry 1 65
Terpenes and their biological relevance
Note the two possible linkage modes:
• “head-to-tail”
• “tail-to-tail”

Figure 8.12 The structure of isoprene (2-methyl-1,3-butadiene)

and the structure of head-to-tail and tail-to-tail linkages.
Isoprene itself can be formed by distillation of natural rubber, a
linear head-to-tail polymer of isoprene units.
 Vitamin A Functions – Visual cycle
11-cis-retinal binds to opsin
 Rhodopsin of rod and cone cells

Exposed to light  nerve impulse

General Biochemistry 1 67
 Vitamin A Functions - Development
• Retinol is oxidized to retinoic acid, which
binds tightly to Retinoic acid receptor (RAR)
• Retinoic acid-RAR binds to DNA and
regulate RNA synthesis
• Vitamin A is essential for normal
differentiation of epithelial tissues
• Retinol and Retinal are essential for normal
reproduction
General Biochemistry 1 68
 Sources of Vitamin A
• Preformed Vitamin A:
– Liver, Kidney
– Cream, butter
– Egg Yolk
• Yellow, orange and dark green vegetables
and fruits are good source of carotenes, a
precursor of vitamin A
General Biochemistry 1 69
 β-carotene
• β-carotene = plant precursor of vitamin A,
oxidation gives 2 retinal
• β-carotene is also an antioxidant

70
 Vitamin A Deficiency
• Night blindness
• Cell keratinization
– Dry skin
– Xerophthalmia (dryness of cornea & conjunctiva)
• Abnormal skeletal development/maintenance
• Immune dysfunction

General Biochemistry 1 71
 Vitamin A Deficiency
Reproductive disorders
• In females:
Increased abortions
Neonates born dead/weak -Deformed young:
no eyeballs; hydrocephalus
• In males: Keratinization of testicular epithelium

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XEROPTHALMIA

General Biochemistry 1 73
 Vitamin D
• Also a terpene
• Ergocalciferol (Vitamin D2) Completely
synthetic form produced by the irradiation
of the plant steroid ergosterol
• Cholecalciferol (Vitamin D3) Produced
photo chemically by the action of sunlight
or ultraviolet light from the precursor
sterol 7-dehydrocholesterol
General Biochemistry 1 74
 Vitamin D

Synthetic, irradiation Biosynthesis in skin by

UV in sun light

General Biochemistry 1 75
Vitamin D3 spontaneous
production in skin

General Biochemistry 1 76
 Vitamin D functions
• Cholecalciferol is transported to liver &
hydroxylated  25-hydroxycholecalciferol
• 25-hydroxycholecalciferol is transported to the
kidney to be hydroxylated to final active form
1,25-dihydroxycholecalciferol
• 1,25-dihydroxycholecalciferol is a hormone to
regulate calcium & phosphate metabolism

General Biochemistry 1 77
 Vitamin D functions
• Calcium homeostasis important in
– muscle contraction,
– nerve impulse transmission,
– blood clotting
– membrane structure
• Phosphorus homeostasis important for
– nucleic, lipids metabolic processes
• Phosphorus and Calcium critical in formation
of bones General Biochemistry 1 78
 Source of Vitamin D

• Human can produce Vitamin

 not strictly a vitamin at all!
• Fish, liver, egg yolk
• Only milk that has added vitamin D
• 1 – 70 years old: 15 mg/day
• Over 70 years old: 20 mg/day

General Biochemistry 1 79
 Vitamin D deficiency
• CHILDREN
– Rickets
– Results in ―bowed‖ legs or knock-knees,
outward bowed chest and knobs on ribs
• ADULT
– Osteomalacia
– Softening of bones, bending of spine, and
bowing of legs
– Osteoporosis
– Associated with fractures
 very serious for geriatrics 80
 α-Tocopherol (Vitamin E)
• Most active form - α-Tocopherol
• A potent antioxidant

General Biochemistry 1 81
 Vitamin E functions
• Molecular details of functions mostly unknown
• Antioxidant: Free radical scavenger
– Protects cell membranes
– Protects LDL from oxidation
– Protection of double bonds in polyunsaturated
fatty acids
– Works in conjunction with selenium
– Stabilize reactions or situations that typically
produce free radicals
General Biochemistry 1 82
 Sources and Vitamin E Deficiency
• Source: vegetable oils, liver and eggs
• Deficiency: Rare
– Erythrocyte hemolysis and hemolytic anemia
– Prolonged deficiency causes neuromuscular
dysfunction; affects the spinal cord and the retina
– Reproductive failure
– Derangement of cell permeability
– Muscular lesions
– Stiff lamb disease (skeletal muscle degeneration)
– Failure to growth General Biochemistry 1 83
 Vitamin K
• K1 = Phylloquinone (Chloroplast)
• K2 = Menaquinone (Bacteria)
• K3 = Menadione (Synthetic – water soluble)

General Biochemistry 1 84
 Vitamin K Functions
• Clotting factors are synthesized in the liver
as inactive precursors
• Vitamin K converts them to their active forms
– Conversion of prothrombin to thrombin
– Formation of fibrinogen to fibrin, leading to
clot formation
• Stimulates bone formation and decreases
bone resorption
General Biochemistry 1 85
 Vitamin K Deficiency
• Primary deficiency rare
• Secondary deficiency:
– fat absorption is impaired(e.g., cystic fibrosis,
Crohn’s disease)
– long-term or high-dose administration of
antibiotics (they kill the bacteria in large intestine)
– Newborn babies with sterile GI tract; single
vitamin K dose given to prevent hemorrhage
• Prolonged clotting time
• Generalized hemorrhages 86