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VITAMINS;
Chemistry and Beyond
Rajendra Dev Bhatt
Assistant Professor / Clinical Biochemist
Dhulikhel Hospital-Kathmandu University Hospital
VITAMINS
Chemically
unrelated organic
nutrients
Classified by their
biological and
chemical activity
and not by their
structure
Cannot be
synthesized in
sufficient
quantities
In our body
Used in many
chemical
reactions in the
body
Unlike organic
food, they do not
enter into tissue
structures nor are
they converted to
energy
Unlike hormones
which are
endogenous, they
are exogenous
Vitamins are defined as
"small organic molecules present in diet which are
required in small amounts. "
Most of the vitamins are not synthesized in the body and
hence they must be supplied in the diet.
However few vitamins are synthesized in the body.
Though most of them are present in diet as such some
are present as precursors.
The precursor forms of vitamins are called as
provitamins. In the body these provitamins are
converted to vitamins.
History of vitamins :
 The story of vitamin dates back to 18th
century.
 Sailors of this period knew that eating of liver
cures a disease called night blindness and
 Eating of lemons cures another disease called
scurvy.
 Also cod liver oil cures a disease called rickets
 In 1912, Sir H.G. Hopkins first identified
Vitamins in MILK and named it as Accessory
factors.
 Funk named the accessory factors as Vitamins
(Vital amines).
Criteria for Vitamins
• Cannot be synthesized in ample amounts in
the body
• Chronic deficiency is likely to cause physical
symptoms
• Symptoms will disappear once the vitamin
level in the body is restored
– Deficiency can cause permanent damage
• 13 compounds meet the above criteria
BIOLOGICAL IMPORTANCE
1. Vitamins are essential for growth, maintenance and
reproduction. However, they are not used for energy
production.
2. Fat soluble vitamins are required for normal colour vision,
blood clotting, bone formation and maintenance of membrane
structure.
3. Most of the water soluble vitamins function as coenzymes or
prosthetic groups of several enzymes involved in
carbohydrate, lipid and amino acid metabolism etc.
4. Vitamins A and D act as steroid hormones.
5. Deficiency of fat soluble vitamins produce night blindness,
skeletal deformation, haemorrhages and hemolysis.
BIOLOGICAL IMPORTANCE (Cont..)
6. Deficiency of water soluble vitamins produce beriberi,
glossitis, pellagra, microcytic anaemia, megaloblastic
anaemia and scurvy.
7. Some vitamin analogs are used as drugs. For example folic
acid analogs are used as anticancer agents and antibiotics.
8. Moderate consumption of some vitamins is found to decrease
occurrence or severity of some diseases.
For example carotenes, Vitamin E and Vitamin D
consumption at moderate evel reduces incidence of cancer
and cardiovascular diseases.
Classification of Vitamins
• Vitamins are divided into two groups.
1. fat soluble vitamins
2. water soluble vitamins.
Fat Soluble Vitamins
• They are vitamins A, D, E and K. They have some common
properties.
They are:
1. Fat soluble.
2. Require bile salts for absorption.
3. Stored in liver.
4. Stable to normal cooking conditions.
5. Excreted in feces.
Water Soluble Vitamins:
• They are members of vitamin B complex and Vitamin C.
Their common properties are
1. Water solubility.
2. Except Vitamin B12others are not stored.
3. Unstable to normal cooking conditions.
4. Excreted in urine.
VITAMINS
CLASSIFICATION
VITAMINS
FAT-SOLUBLE VITAMINS WATER-SOLUBLE VITAMINS
Apolar or hydrophobic Polar
Require normal fat absorption Does not require normal fat
absorption
Stored in the liver or adipose tissue No stable storage form
(except vitamin B-12)
Transported in the blood by
lipoproteins or specific binding
proteins
Does not need protein transporters
Less prone to deficiency More prone to deficiency
manifestations
Prone to toxicity Less prone to toxicity
Excreted through feces Excreted mainly through urine
Absorption and Storage
Water-soluble vitamins
– Absorbed with water and enter
directly into the blood stream
– Most absorbed in the duodenum
and jejunum
– Most are not stored in the body
– Excess intake excreted through
the urine
– Important to consume adequate
amounts daily
Fat-soluble vitamins
– Are absorbed in the
duodenum
– Storage
• Vitamin A is mainly stored in
the liver
• Vitamins K and E are
partially stored in the liver
• Vitamin D is mainly stored in
the fat and muscle tissue
• Can build up in body to
point of toxicity
Digesting and Absorbing Vitamins
THIAMINE B1
Chemistry
THIAMINE B1
Chemistry
• Methylated pyrimidine ring bonded through a
methylene linkage to a thiazole ring
THIAMINE B1
Definition
• Anti-neuritic vitamin
• Anti-beriberi vitamin
• Co-enzyme form:
– Thiamine pyrophosphate (TPP)
– Thiamine co-carboxylase
– Thiamine diphosphate
THIAMINE B1
THIAMINE B1
Properties
THIAMINE B1
Metabolic Role
• Energy-releasing
• Has a central role in carbohydrate
metabolism
• Half-life is 9-18 days
• Sources:
– Meat/fish
– Beans, Nuts, Yeast
– What flour, unpolished rice
– Liver, meat, eggs
THIAMINE B1
Metabolic Roles
Co-enzyme in the decarboxylation of:
Pyruvate
Alpha-
ketoglutarate
Keto acids from
branch-chain
amino acids
THIAMINE B1
Metabolic Roles
• Thiamine triphosphate (TTP)
nerve tissue
metabolism and
conduction
Synthesis of
neurotransmitters
(Ach)
Regulates nerve-
impulse
transmission
THIAMINE B1
Metabolic Roles
Central role of thiamine diphosphate
THIAMINE B1
Metabolic Roles
THIAMINE B1
Deficiency
 May occur in the following conditions:
When the energy
intake is mostly from
rice
Ingestion of foods
containing anti-
thiamine factors.
Pregnancy and
Lactation
Persons who do hard
physical labor
THIAMINE B1
Deficiency
 4 Types of Beriberi
Dry
(peripheral neuritis)
Wet (cardiac
manifestations)
Cerebral
(Wernicke-Korsakoff
syndrome)
Infantile
THIAMINE B1
Deficiency
 Dry Beriberi
 Loss of appetite
 Weight loss
 Muscle-wasting
 Peripheral neuritis
with numbness
 Tingling sensations in
the lower legs and
feet
 Ataxic gait
THIAMINE B1
Deficiency
Wet Beriberi
Vasodilatation, tachycardia, wide
pulse pressure, sweating , warm skin
lactic acidosis
Heart Failure
Orthopnea Pulmonary and
peripheral edema
Vaasodilatation
Shock
THIAMINE B1
Deficiency
 Cerebral Beriberi
 Occurs in alcoholics who
consume less food
 Intelligence disturbance
 Ataxia
 Double vision
 Nystagmus
 Progresses to Wernicke-
Korsakoff psychosis
THIAMINE B1
Deficiency
 Soshin Beriberi
 More rapid form of wet
beriberi
 Acute fulminant CV
beriberi
 Cyanosis of hands and
feet, tachycardia,
distended neck veins,
anxiety
 Rapid deterioration
follows inability of
heart muscle to satisfy
body’s demands
because of its own
injury
THIAMINE B1
Deficiency
THIAMINE B1
Deficiency
 Infantile Beriberi
 Due to low thiamine
content of breast milk
 Anorexia
 Trachycardia
 Vomiting
 Convulsions
 Edema
RIBOFLAVIN B2
Definition I Function
• Synonyms :
– Vitamin B2, Vitamin G, Lactoflavin
• Chemistry:
– Consists of heterocyclic isoalloxazine ring attached
to a sugar alcohol, robitol
RIBOFLAVIN B2
Definition I Function
• Co-enzyme forms:
– FMN Flavin mononucleotide
– FAD Flavin adenine dinucleotide
RIBOFLAVIN B2
Properties
• Colored, flourescent pigment
• Widely used as food additive
• Heat stable but decomposes in the presence
of visible light
RIBOFLAVIN B2
Definition I Function
• RDA :
– Adults: 2.0 mg/day
– Children: 1.2 mg/day
– Pregnant/lactating: 2.0 mg/day
• Sources:
– Milk - 1 quart = 1.7 mg
RIBOFLAVIN B2
Physiologic Roles
• Act as prosthetic group of flavoproteins
• Act as co-enzyme for hydrogen transfer
RIBOFLAVIN B2
Metabolic Roles
• Flavoproteins:
– Enzymes involved in oxidation – reduction reactions
– FAD is required as coenzyme for:
Pyruvate dehydrogenase Carbohydrate breakdown
Succinate dehydrogenase Krebs cycle
Glycerol 3-phosphate
dehydrogenase
Triglyceride synthesis
phospholipid synthesis
Acyl-CoA dehydrogenase Fatty acid breakdown
Glutathione reductase Anti-oxidation
RIBOFLAVIN B2
Metabolic Roles
• Flavoproteins:
– Enzymes involved in oxidation – reduction reactions
– FMN is required for:
• L-amino acid oxidase
• Cytochrome C reductase
Substrate Enzyme Product
Hypoxanthine + O2 +H2O Xanthine Oxidase Xanthine + H2O2
Xanthine + O2 +H2O Xanthine Oxidase Urate + H2O2
Succinate Succinate DH Fumarate
Glycerophosphate Glycerophosphate DH Dihydroxyacetone-PO4
Flavoproteins in electron transport chain
Glutathione reductase – for assaying riboflavin status
Part of pyruvate dehydrogenase and alpha-ketoglutarate
dehydrogenase complexes
RIBOFLAVIN B2
Metabolic Roles
REACTIONS WHERE FAD IS NEEDED AS COENZYME
RIBOFLAVIN B2
Deficiency
• Causes:
– Malnutrition
– Malabsorption
– Anorexia
– Chronic alcoholism
• Assay for Riboflavin status:
– Erythrocyte GSH reductase activity
RIBOFLAVIN B2
Deficiency
• Ariboflavinosis
• Manifestations:
– Epithelial changes in the oral cavity
• Cheilosis or perleche – fissuring of lips
• Glossitis- Magenta tongue
– Corneal Vascularization
– Seborrheic Dermatitis
– Photophobia
• A
RIBOFLAVIN B2
Deficiency
• Angular stomatitis
• Glossitis
RIBOFLAVIN B2
Deficiency
NIACIN B3
Definition I Function
SYNONYMS
– Vitamin B3, Nicotinic acid, pellagra preventive
(PP) factor
– Nicotinamide, niacinamide
• CO-ENZYME FORMS
– Oxidized = NAD and NADP
– Reduced= NADH AND NADPH
NIACIN B3
Definition I Function
• Sources:
– Tryptophan can be
converted to NAD
– 60mg Trp = 1 mg
niacin
– Milk and eggs rich in
tryptophan
NIACIN B3
Definition I Function
• RDA:
– Adults: 16-20 mg/day
– Children: 9-16 mg/day
– Infants: 5-8 mg/day
NIACIN B3
Coenzymes
NIACIN B3
Coenzymes
Examples of Reactions Utilizing NAD and NADP
Substrate Enzyme Product
Lactate Pyruvate
Lactate DH
Malate Oxaloacetate
Malate DH
Hydroxybutyrate Acetoacetate
Beta-OH- butyrate DH
Glucose Gluconate
Glucose DH
Isocitrate Alpha-ketoglutarate
Isocitrate DH
Glutamate Alpha-ketoglutarate +
AmmoniaGlutamate DH
NIACIN B3
Deficiency
• CLINICAL EFFECTS:
Pellagra “rough skin” – 3D’s
– Dermatitis –skin exposed to sunlight
• Casal’s necklace
• Gloves and stockings lesions
– Diarrhea
– Dementia
– Stomatitis, magenta tongue
– Severe cases, GIT hemorrhagic
* ineffective repair and regeneration of epithelial cells
NIACIN B3
Deficiency
Dermatitis of Pellagra
Casal’s Necklace
NIACIN B3
Deficiency
Dermatitis of Pellagra
Gloves and stocking appearance
NIACIN B3
Excess
Toxicity
• 1-6 grams ( hyperlipidemia)
• Dilatation of blood vessels
• Flushing
• Skin irritation
• Liver damage
Some times it is Not strictly considered as
vitamin.
Although the body cannot make vitamin
B-3, it can convert an amino acid called
tryptophan into vitamin B-3.
PYRIDOXINE B6
Definition I Function
• SYNONYMS:
– Amino acid metabolism vitamin
– Rat anti-dermatitis factor
– Adermin (essential for AA and Carbohydrate metabolism)
– Rat anti-pellagra factor
• CO-ENZYME FORMS:
–Pyridoxal phosphate and pyridoxinamine
phosphate
–Major excretory product: 4-Pyridoxic
acid
PYRIDOXINE B6
Definition I Function
• FUNCTION
– Precursor of pyridoxal phosphate
– Coenzyme for several enzymes for AMINO ACID
METABOLISM
• DEFICIENCY
– Intake of Isoniazid
PYRIDOXINE B6
Definition I Function
• Sources:
– Whole grain & legumes
– Poultry & Fish
– Potatoes
– Organ meats
– Eggs
• RDA:
– Adults: 2.2 mg/day
– Children: 1.2 mg/day
– Infants: 3.0 mg/day
PYRIDOXINE B6
Food Sources
• RDA: Roughly proportional to the
protein content of the diet
– 0.02 mg/g of protein intake
– 1.5-2.0 mg/day for normal adult
– Increased during pregnancy and
lactation
PYRIDOXINE B6
Definition I Function
PYRIDOXINE B6
Definition I Function
• Physiological importance:
– Amino acid metabolism
– Synthesis of ceramide
– Synthesis of the
neurotransmitters
serotonin, dopamine,
epinephrine, norepinephrine
& GABA.
– Synthesis of the histamine.
– Synthesis of porphyrins
– Glycogenolysis - phosphorylase
PYRIDOXINE B6
Definition I Function
• Co-enzyme in protein metabolism
– Decarboxylation
– Conversion of 3-hydroxykynurenine to 3-OH-anthranilic acid
– Conversion of Tryptophan to serotonin
– Deamination – serine and threonine
– Transamination – acts as an amino group carrier
PYRIDOXINE B6
Definition I Function
PYRIDOXINE B6
Definition I Function
• Co-enzyme in protein metabolism
– Trans-sulfuration
• transfer of sulfur from methionine to serine to form cysteine
– Conversion of cysteine to pyruvate
• via cysteine desulfhydrase
– Interconversion of glycine and serine
– Decarboxylation of alpha-amino-beta-ketoadipic acid to delta-
aminolevulinic acid
PYRIDOXINE B6
Definition I Function
• Co-enzyme in carbohydrate and fat metabolism
– Conversion of Linoleic to Arachidonic acid
– Cofactor in the activity of phosphorylase
– Cofactor in the metabolism of unsaturated fatty acids and
cholesterol
– Synthesis of sphingolipids necessary for myelin formation
PYRIDOXINE B6
Definition I Function
• Enzymes :
Amino transferases amino acid breakdown
Glycogen phosphorylase glycogen breakdown
Serine dehydratase feeding serine's
breakdown product to
gluconeogenesis
Aminolevulinic acid
synthase
porphyrin synthesis
PYRIDOXINE B6
Definition I Function
• Essential for the maintenance of the integrity of :
– Neuronal tissues
– Production of anti-bodies
– Bone development
PLP
PLP
PLP
PLP
PYRIDOXINE B6
Deficiency
• Clinical features:
–Epileptiform seizures in infants
–Pellagra-like skin lesions
–GIT involvement- distention,
vomiting , diarrhea
–Anemia- hypochromic and
microcytic
PYRIDOXINE B6
Biochemistry
• Important biochemical finding in Vitamin B6
deficiency:
– Increased excretion of urinary oxalates
– Mechanism:
decreased conversion of glycine glyoxalate broken down to
oxalic acid increased possibility of forming oxalate stones
PANTOTHENIC ACID
Definition
• SYNONYMS:
– “everywhere vitamin”
– Filtrate factor
• ROYAL JELLY
PANTOTHENIC ACID
Function
• FUNCTION
– Component of Coenzyme A
• RDA:
– Adults: 5-10 mg/day
– Children: 4-5 mg/day
– Infants: 1-2 mg/day
PANTOTHENIC ACID
Function
Substrate Enzyme Product
Pyruvate + CoASH
Pyruvate DH complex
Acetyl CoA
α-ketoglutarate- CoASH
Alpha-KG DH complex
Succinyl CoA
Fattyl acid + CoASH
Thiokinase
Acetyl-CoA
Ketoacyl CoA + CoASH
Thiolase
Acyl CoA +
Acetyl CoA
Detoxification of benzoic acid
Synthesis of bile salts
PANTOTHENIC ACID
Function
• As Acetyl CoA
Combines with
oxaloacetic acid to
form citric acid –
first step in the
Kreb’s cycle
Combines with
choline to form
acetylcholine
Combines with
sulfonamide drugs
to facilitate their
excretion
Precursor of
cholesterol / steroid
hormones
Activation of some
amino acids :
valine, leucine and
isoleucine
Essential function in
lipid metabolism
PANTOTHENIC ACID
Function
• As Succiny CoA
– Involved in heme biosynthesis
• As Acyl Carrier Protein
– Involved in fatty acid biosynthesis
– Extra-mitochondrial lipogenesis
Acetyl CoA
PANTOTHENIC ACID
Deficiency
• Rare because:
– Very widespread in natural foods
– Most symptoms are vague and mimic those of other B vitamin
deficiencies
BIOTIN B7
Definition
• SYNONYMS:
– Vitamin B7; anti-egg white injury factor
• CHARACTERISTICS:
– Widely distributed in natural foods
– From synthesis of bacteria - deficiency is caused
by defects in utilization and not dietary
– Long-term antibiotic treatment or excessive
consumption of raw egg
BIOTIN B7
Definition
• AVIDIN – a protein in raw egg white which
combines very tightly with biotin, preventing
its absorption
BIOTIN B7
Function
• FUNCTION
– Coenzymes for carboxylation reactions
– Carrier of activated carbon dioxide
• FOOD SOURCES
– Almost all foods, liver, milk, egg yolk
– 400 µg/day
• DEFICIENCY
– Uncommon
– Raw egg avidin prevents absorption of Biotin
BIOTIN B7
Function
CARBOXYLATION REACTIONS:
BIOTIN B7
Substrate Enzyme Product
Acetyl CoA Malonyl CoA
acetyl CoA
carboxylase
Propionyl CoA
Propionyl CoA
carboxylase
Methylmalonyl
CoA
Pyruvate
pyruvate
carboxylase
Oxaloacetic acid
Biotin
Biotin
BIOTIN B7
Deficiency
• Man (rare)
– Fine scaly skin desquamation
(peeling)
– Anorexia (lack or loss of
appetite for food)
– Nausea
– Lassitude (lack of energy)
– Muscle pains
– Depression
– Alopecia (baldness)
– Graying of hair
FOLIC ACID B9
Facts
• SYNONYMS:
– Vit B9, Folate, Folacin, PGA (Pteroylglutamic acid)
• FUNCTION
– One-Carbon metabolism
– Essential in biosynthesis of thymidine, AA, and
purine
FOLIC ACID B9
Facts
• FOOD SOURCES
– Green leafy vegetables, liver, lima beans, whole
grain cereals
• DEFICIENCY
– Growth failure
– Megaloblastic anemia
– Neural tube defects
FOLIC ACID B9
Structure
FOLIC ACID B9
Functions
– Carrier of one-carbon group moieties.
Form Formula Name
Most reduced CH3 Methyl
Intermediate CH2 Methylene
Most oxidized CHO Formyl
CHNH Formimino
CH= methenyl
FOLIC ACID B9
Forms
Form Decription
N5-methyl- THFA Most prevalent form transported in the blood
N5, N10-methylene THFA Provides methyl group in the formation of
thymidylate for DNA synthesis and erythrocyte
formation
N10 formy; THFA Provides C atom that becomes C2 of purine
nucleus
N5-formimino THFA Histidine catabolism
N10-hydroyxymethyl THFA Thymine synthesis
FOLIC ACID B9
Function
FOLIC ACID B9
Function
400 ug folate supplement
FOLIC ACID B9
Deficiency
Blood Cell Macrocytic Anemia- impaired production
Blood Cell Microcytic Anemia
Results when RBC are unable
to divide…
VITAMIN B12
Definition
• SYNONYMS:
– Antipernicious anemia vitamin
– Cobalamin
– Extrinsic Factor of Castle
– Erythrocyte Maturation Factor
• CHEMISTRY:
VITAMIN B12
Chemistry
• Consists of:
1. Corrin ring system - central
portion of the molecule:
similar to a porphyrin ring
2. 5,6-dimethylbenzimidazole
riboside
3. Aminopropanolol
4. Propionic acid
5. Cobalt-occupies the center
of the corrin ring system
1
5
43
2
VITAMIN B12
Function
• FUNCTION
– Synthesis of methionine
– Isomerization of methylmalonyl CoA
VITAMIN B12
Function
– Involved in the rearrangement of
methylmalonyl CoA to succinyl CoA by
methylmalonyl CoA isomerase
•Involved in the transfer of a methyl group from
methylTHFA to homocysteine to form
methionine .
VITAMIN B12
Sources ІDeficiency
• FOOD SOURCES
– Synthesized by microorganisms in the bacterial flora
– Liver, whole milk, eggs
– fresh shrimp, pork, chicken
• RDA
– Children: 2ug/day
– Adults 3 ug/day
– Pregnancy and lactation: 4 ug/day
• DEFICIENCY
– Abnormal fatty acid synthesis
– Cell membrane defects/Neurological abnormalities
– Pernicious anemia
VITAMIN B12
Forms
Forms Content
Cobalamin Without cyanide
Cyanocobalamin with cyanide group
Hydroxocobalamin with hydroxyl group, more active
in enzyme systems; retained
longer in the body
Methylcobalamin major form in the plasma
5’-deoxyadenosyl
cobalamin
readily binds to plasma-binding
proteins
VITAMIN B12
Deficiency
• Causes:
– Chronic dietary deficiency of vitamin B-12.
– Poor absorption due to lack of intrinsic factor.
• Presence of antibodies to the intrinsic factor in the
gastric juice.
• Lack of secretion of intrinsic factor (due to gastric
mucosal
cell atrophy or due to total gastrectomy.
• Extensive resection of the small intestines.
– Increased requirements as in pregnancy.
VITAMIN B12
Deficiency
• Clinical effects: “Pernicious Anemia”
• No healthy RBC
• Characterized by:
– Megaloblastic or macrocytic anemia.
– Lesions of the nervous system
– Mucosal atrophy and inflammation of the
tongue
(glossitis), mouth (stomatitis) and pharynx
(pharyngitis)
ASCORBIC ACID (Vitamin C)
Facts
• Anti-scorbutic vitamin
• Very sensitive to oxidation
• Rapidly destroyed by alkalies
• Freezing has no deleterious effect
• Strong reducing agent
• Drying vegetables usually results in loss of
vitamin C.
ASCORBIC ACID
Facts
• Sources:
– Citrus fruits
– Tomatoes
– Strawberries
– Green vegetables
– Guava fruit
– Green pepper
• RDA:
– Adults: 60 mg/day
– Children: 40 mg/day
ASCORBIC ACID
Facts
ASCORBIC ACID
Metabolic roles
Hydroxylation of
Proline and
Lysine in collagen
formation.
Hydroxylation of
tryptophan
Synthesis of
norephinephrine
Tyrosine
metabolism
Hydroxylation of
steroids in the
adrenal cortex
Serves as a
reductant of
ferric to ferrous
ion
Involved in the
conversion of
folic acid to
active THFA
Involved in the
hydroxylationof
cholesterol to
cholic acid
Acts as regulator
of cholesterol
metabolism
ASCORBIC ACID
Function
• Major function of vitamin C
– coenzyme in the formation of tissue collagen or intracellular cement
substance
ASCORBIC ACID
Function
• Major function of vitamin C
– coenzyme in the formation of tissue collagen or intracellular cement
substance
ASCORBIC ACID
Deficiency
• Spongy gums
• Poor wound healing
ASCORBIC ACID
Deficiency
• Splinter hemorrhages in nails
• subcutaneous hemorrhages
ASCORBIC ACID
Deficiency
• swelling at the ends of long bones
FAT-SOLUBLE VITAMINS
Structure
• Vitamin A
• Vitamin D
• Vitamin K
• Vitamin E
retinol, B-carotenes
cholecalciferol
phylloquinones, menaquinones
tocopherols
VITAMIN A Retinol
Structure
• Retinol and retinoic acid – act like steroid
hormones
• Retinalehyde is a component of Rhodposin
• Retinoic acid participates in glycoprotein
synthesis
VITAMIN A Retinol
Function
• Provitamin - β carotene
• FUNCTION
– Maintenance of reproduction
– Maintenance of vision
– Promotion of growth
– Gene expression
– Treatment of psoriasis, acne, cancers
• FOOD SOURCES
– Liver, kidney, cream, butter, egg yolk
– Yellow and dark green vegetables



Dietary Vitamin A, from
animal sources is available in
the form of Retinyl esters,
which is hydrolyzed to retinol
and fatty acid by pancreatic
hydrolases
The absorption of retinol
requires the presence of bile
salts
In the intestinal cells, retinol
is esterified back and
secreted with chylomicrons
• The liver contains approximately 90% of the vitamin
A reserves and secretes vitamin A in the form of
retinol, which is bound to retinol- binding
protein.
•
•
The retinol-binding protein complex interacts
with a second protein, Transthyretin.
This trimolecular complex functions to prevent
vitamin A from being filtered by the kidney
glomerulus, to protect the body against the
toxicity of retinol and to allow retinol to be
taken up by specific cell-surface receptors that
recognize retinol-binding protein.
• In the retina, retinaldehyde functions as the
prosthetic group of the light-sensitive opsin
proteins, forming Rhodopsin (in rods) and
iodopsin (in cones).
•
•
•
Any one cone cell contains only one type of
opsin, and is sensitive to only one color.
The absorption of light by Rhodopsin causes
isomerization of the retinaldehyde from 11-cis to
all-trans, and a conformational change in opsin.
This results in the release of retinaldehyde from
the protein, and the initiation of a nerve
impulse.


The formation of the initial excited form of
Rhodopsin, bathorhodopsin, occurs within
pico-seconds of illumination.
There are then a series of conformational
changes leading to the formation of
metarhodopsin II, which initiates a guanine
nucleotide amplification cascade and then a
nerve impulse.
 The final step is hydrolysis to release all-
trans-retinaldehyde and opsin.


The key to initiation of the visual cycle is the
availability of 11-cis-retinaldehyde, and
hence vitamin A.
In deficiency, both the time taken to adapt
to darkness and the ability to see in poor
light are impaired.
VITAMIN D
Facts
• FUNCTION
– 1,25-dihydrocholecalciferol- a steroid hormone
– Stimulates gene expression or repress gene
transcription
– Regulates plasma levels of calcium and
phosphorus
Vitamin D Synthesis
•Vitamin D in reality is a hormone and is a metabolic
product of the cholesterol biosynthetic pathway
•Vitamin D3, a cholecalciferol is synthesized de novo by
the exposure of skin to sunlight that converts 7-
dehydrocholesterol to vitamin D3
•Vitamin D3 is then converted in liver, to 25-
hydroxycholecalciferol (25-OH- D3) by the enzyme 25-
hydroxylase - still an inactive form
•25-OH- D3 is the blood test used to assess adequacy of
vitamin D stores in the body
•In the kidney, renal 1 α-hydroxylase hydrolyses 25-OH-
D3 to form 1,25-dihydroxycholecalciferol (1,25-[OH]2-
D3) – the biologically active form (PTH stimulates this
enzyme)
Vitamin D from diet
Vitamin D is relatively rare in most typical
foods.
The only common dietary source of vitamin
D are multivitamins , supplements and
vitamin D fortified milk.
Cod liver oil is also a source of vitamin D
Vitamin D
The actions of Vitamin D
1. Enhances calcium absorption from the
intestine
2. Facilitates calcium reabsorption in the kidney
3. Increases bone calcification and
mineralization
4. In excess, mobilizes bone calcium and
phosphate.
VITAMIN D
Action
Response to low
plasma calcium
VITAMIN D
Deficiency
• DEFICIENCY
– Rickets
– Osteomalacia
(demineralization of
bone)
• TOXICITY
– Most toxic of all vitamins
– Deposition of calcium in
organs and arteries,
kidney stones
Vitamin K
 Three compounds have the biological activityof vitamin
K
 Phylloquinone (Vitamin K1), the normal dietary
source, found in green vegetables
 Menaquinones (vitamin K2), synthesized by
intestinal bacteria,with differing lengths of side
chain;
 and Menadione and menadiol diacetate, synthetic
compounds thatcan be metabolized tophylloquinone.
Dietary Sources
 Green leafyvegetables such as kaleand
spinach,
 Margarine and liver.
 Vegetableoilsand particularlyolive, canola,
and soybean oils.
 Some amount is contributed byintestinal
bacteria
6
Absorption, Transportation and
Storage
 Absorption takes place in small
intestine in the presence of bile
salts.
 The transportation from
intestineis carried out
throughchylomicrons.
 Storage occurs in liver and from
liver transportation to
peripheral cells is carried out
bound with betalipoproteins
(VLDL).
1
3
Recommended daily allowance (RDA)
 The averagedaily
allowance is 50-120
mcg/day.
 Requirement increases in –
 Liverdisorders
 Patients on prolonged
antibiotictherapy, and
Orlistat (weight loss
medication)
Functions of Vitamin K
Coagulation
Bone Synthesis
Prevention of
atherosclerosis
1
3
Vitamin K deficiency
Vitamin K
deficienc
y
Dietary
deficiency
Fat
malabsorp
tion
Surgical
interventi
ons of
intestine Chronic
liver
diseases
Prolonged
intake of
antibiotics
 Chemical nature:
 Vitamin E is chemically known as tocopherol
(Greek: tocos=childbirth, piro=to bear and
ol=alcohol)
• An alcohol was capable to prevent reproductive
failure in animals
• Hence it is known as anti-sterility vitamin
• Chemistry:
• Vitamin E is the name given to group of tocopherols
and tocotrienols
 About 8 tocopherols have been identified
 Alpha- tocopherol is most active
 The tocopherols are derivatives of 6-hydroxy
chromane (tocol) ring with isoprenoid side chain
 The antioxidant property is due to the chromane
ring
ABSORPTION
 Vitamin E is absorbed along with fat in the upper
small intestine
 Mechanism: Vitamin E combines with Bile salts
(micelles) to form mixed micelle and taken up by
the mucosal cell
 In the mucosal cell, it is incorporated into
chylomicrons
Biochemical functions
1.Vitamin E is essential for membrane structure
and integrity of the cell, hence it is membrane
antioxident
2. It prevents the peroxidation of PUFA
3.It protects the RBC from hemolysis by oxidizing
agents (H2O2)
4.It is associated with reproductive function and
prevents sterility
5.Vitamin E preserves and maintains germinal
epithelium of gonads for proper reproductive
function
6.It increases the synthesis of heme by enhancing the activity
of enzyme – δ aminolevulinic acid (ALA)
synthase and ALAdehydratase
7. It is required for cellular respiration –through ETC
(Stabilize coenzyme Q)
8. Vitamin E prevents the oxidation of Vitamin A and
carotenes
9. Vitamin E prevents oxidation of LDL, Oxidized LDL
promotes heart diseases
 Males
 Females
 Pregnancy
 Lactation
-10 mg/day
- 8 mg/day
- 10 mg/day
- 12 mg/day
 15 mg of vitamin E is equivalent to 33 IU
 Pharmacological dose is 200-400 IU/day
 Sources:
 Rich sources are vegetable oils
 Includes germ oil, sunflower oil, corn oil and
margarine
VITAMINS
Definition I Function
VITAMIN FUNCTIONS DEFICIENCY DISEASE
A Retinol,
β-carotene
Visual pigments in the retina;
regulation of gene expression
and cell differentiation;
Antioxidant
Night blindness,
xerophthalmia;
keratinization of skin
D Calciferol Maintenance of calcium balance;
enhances intestinal absorption of
Ca++ and mobilized biomineral
Rickets = poor
mineralization of bones;
Osteomalacia = bone
demineralization
E Tocopherols
Tocotrienols
Antioxidant, especially incell
membranes
Extremely rare - serious
neurologic dysfunction
K Phylloquinone
Menaquinone
Coenzyme in formation of γ-
carboxyglutamate in enzymes of
blood clotting and bonematrix
Impaired blood clotting,
hemorrhagic disease
VITAMINS
Definition I Function
VITAMIN FUNCTIONS DEFICIENCY DISEASE
B1 Thiamin Coenzyme in pyruvate and α-
ketoglutarate DH, and
transketolase; poorly defined
function in nerve conduction
Peripheral nerve damage
(beriberi) or CNS lesions
(Wernicke-Korsakoff
syndrome)
B2 Riboflavin Coenzyme in redox reactions;
prosthetic group of
flavoproteins
Lesions of corner of
mouth, lips and tongue,
seborrheic dermatitis
B3 Niacin
Nicotinic acid
Nicotinamide
Coenzyme in redox reactions;
functional part of NAD and
NADP
Pellagra- photosensitive
dermatitis, depressive
psychosis
Energy-Releasing
VITAMINS
Definition I Function
Energy-Releasing
VITAMIN FUNCTIONS DEFICIENCY DISEASE
Pantothenic Acid Functional part of CoA and acyl
carrier protein: fatty acid
synthesis and metabolism
Biotin Coenzyme in carboxylation
reactions in gluconeogenesis
and fatty acid synthesis
Impaired fat and CHO
metabolism, dermatitis
VITAMINS
Definition I Function
VITAMIN FUNCTIONS DEFICIENCY DISEASE
Folic acid Coenzyme in transfer of one-
carbon fragments
Megaloblastic anemia
B12 Cobalamin Coenzyme in transfer of one-
carbon fragments and
metabolism of folic acid
Pernicious anemia =
megaloblastic anemia
with degeneration of the
spinal cord
Hematopoeitic
VITAMINS
Definition I Function
VITAMIN FUNCTIONS DEFICIENCY DISEASE
B6
Pyridoxine
Pyridoxal
Pyridoxamine
Coenzyme in transamination &
decarboxylation of AA and
glycogen phosphorylase; role
in steroid hormone action
Disorders of AA
metabolism, convulsions
C Ascorbic Acid Coenzyme in hydroxylation of
proline and lysine in collagen
synthesis; antioxidant;
enhances iron absorption
Scurvy- impaired wound
healing, loss of dental
cement, subcutaneous
hemorrhage
Other functions
VITAMINS
Definition I Function
• w
Biochemistry of Vitamins for Medical Students-Rajendra
Biochemistry of Vitamins for Medical Students-Rajendra
Biochemistry of Vitamins for Medical Students-Rajendra

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Biochemistry of Vitamins for Medical Students-Rajendra

  • 1. VITAMINS; Chemistry and Beyond Rajendra Dev Bhatt Assistant Professor / Clinical Biochemist Dhulikhel Hospital-Kathmandu University Hospital
  • 2. VITAMINS Chemically unrelated organic nutrients Classified by their biological and chemical activity and not by their structure Cannot be synthesized in sufficient quantities In our body Used in many chemical reactions in the body Unlike organic food, they do not enter into tissue structures nor are they converted to energy Unlike hormones which are endogenous, they are exogenous
  • 3. Vitamins are defined as "small organic molecules present in diet which are required in small amounts. " Most of the vitamins are not synthesized in the body and hence they must be supplied in the diet. However few vitamins are synthesized in the body. Though most of them are present in diet as such some are present as precursors. The precursor forms of vitamins are called as provitamins. In the body these provitamins are converted to vitamins.
  • 4. History of vitamins :  The story of vitamin dates back to 18th century.  Sailors of this period knew that eating of liver cures a disease called night blindness and  Eating of lemons cures another disease called scurvy.  Also cod liver oil cures a disease called rickets  In 1912, Sir H.G. Hopkins first identified Vitamins in MILK and named it as Accessory factors.  Funk named the accessory factors as Vitamins (Vital amines).
  • 5. Criteria for Vitamins • Cannot be synthesized in ample amounts in the body • Chronic deficiency is likely to cause physical symptoms • Symptoms will disappear once the vitamin level in the body is restored – Deficiency can cause permanent damage • 13 compounds meet the above criteria
  • 6. BIOLOGICAL IMPORTANCE 1. Vitamins are essential for growth, maintenance and reproduction. However, they are not used for energy production. 2. Fat soluble vitamins are required for normal colour vision, blood clotting, bone formation and maintenance of membrane structure. 3. Most of the water soluble vitamins function as coenzymes or prosthetic groups of several enzymes involved in carbohydrate, lipid and amino acid metabolism etc. 4. Vitamins A and D act as steroid hormones. 5. Deficiency of fat soluble vitamins produce night blindness, skeletal deformation, haemorrhages and hemolysis.
  • 7. BIOLOGICAL IMPORTANCE (Cont..) 6. Deficiency of water soluble vitamins produce beriberi, glossitis, pellagra, microcytic anaemia, megaloblastic anaemia and scurvy. 7. Some vitamin analogs are used as drugs. For example folic acid analogs are used as anticancer agents and antibiotics. 8. Moderate consumption of some vitamins is found to decrease occurrence or severity of some diseases. For example carotenes, Vitamin E and Vitamin D consumption at moderate evel reduces incidence of cancer and cardiovascular diseases.
  • 8. Classification of Vitamins • Vitamins are divided into two groups. 1. fat soluble vitamins 2. water soluble vitamins. Fat Soluble Vitamins • They are vitamins A, D, E and K. They have some common properties. They are: 1. Fat soluble. 2. Require bile salts for absorption. 3. Stored in liver. 4. Stable to normal cooking conditions. 5. Excreted in feces.
  • 9. Water Soluble Vitamins: • They are members of vitamin B complex and Vitamin C. Their common properties are 1. Water solubility. 2. Except Vitamin B12others are not stored. 3. Unstable to normal cooking conditions. 4. Excreted in urine.
  • 11. VITAMINS FAT-SOLUBLE VITAMINS WATER-SOLUBLE VITAMINS Apolar or hydrophobic Polar Require normal fat absorption Does not require normal fat absorption Stored in the liver or adipose tissue No stable storage form (except vitamin B-12) Transported in the blood by lipoproteins or specific binding proteins Does not need protein transporters Less prone to deficiency More prone to deficiency manifestations Prone to toxicity Less prone to toxicity Excreted through feces Excreted mainly through urine
  • 12. Absorption and Storage Water-soluble vitamins – Absorbed with water and enter directly into the blood stream – Most absorbed in the duodenum and jejunum – Most are not stored in the body – Excess intake excreted through the urine – Important to consume adequate amounts daily Fat-soluble vitamins – Are absorbed in the duodenum – Storage • Vitamin A is mainly stored in the liver • Vitamins K and E are partially stored in the liver • Vitamin D is mainly stored in the fat and muscle tissue • Can build up in body to point of toxicity
  • 15. THIAMINE B1 Chemistry • Methylated pyrimidine ring bonded through a methylene linkage to a thiazole ring
  • 16. THIAMINE B1 Definition • Anti-neuritic vitamin • Anti-beriberi vitamin • Co-enzyme form: – Thiamine pyrophosphate (TPP) – Thiamine co-carboxylase – Thiamine diphosphate
  • 19. THIAMINE B1 Metabolic Role • Energy-releasing • Has a central role in carbohydrate metabolism • Half-life is 9-18 days • Sources: – Meat/fish – Beans, Nuts, Yeast – What flour, unpolished rice – Liver, meat, eggs
  • 20. THIAMINE B1 Metabolic Roles Co-enzyme in the decarboxylation of: Pyruvate Alpha- ketoglutarate Keto acids from branch-chain amino acids
  • 21. THIAMINE B1 Metabolic Roles • Thiamine triphosphate (TTP) nerve tissue metabolism and conduction Synthesis of neurotransmitters (Ach) Regulates nerve- impulse transmission
  • 22. THIAMINE B1 Metabolic Roles Central role of thiamine diphosphate
  • 24.
  • 25. THIAMINE B1 Deficiency  May occur in the following conditions: When the energy intake is mostly from rice Ingestion of foods containing anti- thiamine factors. Pregnancy and Lactation Persons who do hard physical labor
  • 26. THIAMINE B1 Deficiency  4 Types of Beriberi Dry (peripheral neuritis) Wet (cardiac manifestations) Cerebral (Wernicke-Korsakoff syndrome) Infantile
  • 27. THIAMINE B1 Deficiency  Dry Beriberi  Loss of appetite  Weight loss  Muscle-wasting  Peripheral neuritis with numbness  Tingling sensations in the lower legs and feet  Ataxic gait
  • 28.
  • 29. THIAMINE B1 Deficiency Wet Beriberi Vasodilatation, tachycardia, wide pulse pressure, sweating , warm skin lactic acidosis Heart Failure Orthopnea Pulmonary and peripheral edema Vaasodilatation Shock
  • 30.
  • 31. THIAMINE B1 Deficiency  Cerebral Beriberi  Occurs in alcoholics who consume less food  Intelligence disturbance  Ataxia  Double vision  Nystagmus  Progresses to Wernicke- Korsakoff psychosis
  • 32. THIAMINE B1 Deficiency  Soshin Beriberi  More rapid form of wet beriberi  Acute fulminant CV beriberi  Cyanosis of hands and feet, tachycardia, distended neck veins, anxiety  Rapid deterioration follows inability of heart muscle to satisfy body’s demands because of its own injury
  • 34. THIAMINE B1 Deficiency  Infantile Beriberi  Due to low thiamine content of breast milk  Anorexia  Trachycardia  Vomiting  Convulsions  Edema
  • 35. RIBOFLAVIN B2 Definition I Function • Synonyms : – Vitamin B2, Vitamin G, Lactoflavin • Chemistry: – Consists of heterocyclic isoalloxazine ring attached to a sugar alcohol, robitol
  • 36. RIBOFLAVIN B2 Definition I Function • Co-enzyme forms: – FMN Flavin mononucleotide – FAD Flavin adenine dinucleotide
  • 37. RIBOFLAVIN B2 Properties • Colored, flourescent pigment • Widely used as food additive • Heat stable but decomposes in the presence of visible light
  • 38. RIBOFLAVIN B2 Definition I Function • RDA : – Adults: 2.0 mg/day – Children: 1.2 mg/day – Pregnant/lactating: 2.0 mg/day • Sources: – Milk - 1 quart = 1.7 mg
  • 39. RIBOFLAVIN B2 Physiologic Roles • Act as prosthetic group of flavoproteins • Act as co-enzyme for hydrogen transfer
  • 40. RIBOFLAVIN B2 Metabolic Roles • Flavoproteins: – Enzymes involved in oxidation – reduction reactions – FAD is required as coenzyme for: Pyruvate dehydrogenase Carbohydrate breakdown Succinate dehydrogenase Krebs cycle Glycerol 3-phosphate dehydrogenase Triglyceride synthesis phospholipid synthesis Acyl-CoA dehydrogenase Fatty acid breakdown Glutathione reductase Anti-oxidation
  • 41. RIBOFLAVIN B2 Metabolic Roles • Flavoproteins: – Enzymes involved in oxidation – reduction reactions – FMN is required for: • L-amino acid oxidase • Cytochrome C reductase
  • 42. Substrate Enzyme Product Hypoxanthine + O2 +H2O Xanthine Oxidase Xanthine + H2O2 Xanthine + O2 +H2O Xanthine Oxidase Urate + H2O2 Succinate Succinate DH Fumarate Glycerophosphate Glycerophosphate DH Dihydroxyacetone-PO4 Flavoproteins in electron transport chain Glutathione reductase – for assaying riboflavin status Part of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes RIBOFLAVIN B2 Metabolic Roles REACTIONS WHERE FAD IS NEEDED AS COENZYME
  • 43. RIBOFLAVIN B2 Deficiency • Causes: – Malnutrition – Malabsorption – Anorexia – Chronic alcoholism • Assay for Riboflavin status: – Erythrocyte GSH reductase activity
  • 44. RIBOFLAVIN B2 Deficiency • Ariboflavinosis • Manifestations: – Epithelial changes in the oral cavity • Cheilosis or perleche – fissuring of lips • Glossitis- Magenta tongue – Corneal Vascularization – Seborrheic Dermatitis – Photophobia
  • 47. NIACIN B3 Definition I Function SYNONYMS – Vitamin B3, Nicotinic acid, pellagra preventive (PP) factor – Nicotinamide, niacinamide • CO-ENZYME FORMS – Oxidized = NAD and NADP – Reduced= NADH AND NADPH
  • 48. NIACIN B3 Definition I Function • Sources: – Tryptophan can be converted to NAD – 60mg Trp = 1 mg niacin – Milk and eggs rich in tryptophan
  • 49. NIACIN B3 Definition I Function • RDA: – Adults: 16-20 mg/day – Children: 9-16 mg/day – Infants: 5-8 mg/day
  • 52. Examples of Reactions Utilizing NAD and NADP Substrate Enzyme Product Lactate Pyruvate Lactate DH Malate Oxaloacetate Malate DH Hydroxybutyrate Acetoacetate Beta-OH- butyrate DH Glucose Gluconate Glucose DH Isocitrate Alpha-ketoglutarate Isocitrate DH Glutamate Alpha-ketoglutarate + AmmoniaGlutamate DH
  • 53. NIACIN B3 Deficiency • CLINICAL EFFECTS: Pellagra “rough skin” – 3D’s – Dermatitis –skin exposed to sunlight • Casal’s necklace • Gloves and stockings lesions – Diarrhea – Dementia – Stomatitis, magenta tongue – Severe cases, GIT hemorrhagic * ineffective repair and regeneration of epithelial cells
  • 54. NIACIN B3 Deficiency Dermatitis of Pellagra Casal’s Necklace
  • 55. NIACIN B3 Deficiency Dermatitis of Pellagra Gloves and stocking appearance
  • 56. NIACIN B3 Excess Toxicity • 1-6 grams ( hyperlipidemia) • Dilatation of blood vessels • Flushing • Skin irritation • Liver damage
  • 57. Some times it is Not strictly considered as vitamin. Although the body cannot make vitamin B-3, it can convert an amino acid called tryptophan into vitamin B-3.
  • 58. PYRIDOXINE B6 Definition I Function • SYNONYMS: – Amino acid metabolism vitamin – Rat anti-dermatitis factor – Adermin (essential for AA and Carbohydrate metabolism) – Rat anti-pellagra factor • CO-ENZYME FORMS: –Pyridoxal phosphate and pyridoxinamine phosphate –Major excretory product: 4-Pyridoxic acid
  • 59. PYRIDOXINE B6 Definition I Function • FUNCTION – Precursor of pyridoxal phosphate – Coenzyme for several enzymes for AMINO ACID METABOLISM • DEFICIENCY – Intake of Isoniazid
  • 60. PYRIDOXINE B6 Definition I Function • Sources: – Whole grain & legumes – Poultry & Fish – Potatoes – Organ meats – Eggs • RDA: – Adults: 2.2 mg/day – Children: 1.2 mg/day – Infants: 3.0 mg/day
  • 61. PYRIDOXINE B6 Food Sources • RDA: Roughly proportional to the protein content of the diet – 0.02 mg/g of protein intake – 1.5-2.0 mg/day for normal adult – Increased during pregnancy and lactation
  • 63. PYRIDOXINE B6 Definition I Function • Physiological importance: – Amino acid metabolism – Synthesis of ceramide – Synthesis of the neurotransmitters serotonin, dopamine, epinephrine, norepinephrine & GABA. – Synthesis of the histamine. – Synthesis of porphyrins – Glycogenolysis - phosphorylase
  • 64. PYRIDOXINE B6 Definition I Function • Co-enzyme in protein metabolism – Decarboxylation – Conversion of 3-hydroxykynurenine to 3-OH-anthranilic acid – Conversion of Tryptophan to serotonin – Deamination – serine and threonine – Transamination – acts as an amino group carrier
  • 66. PYRIDOXINE B6 Definition I Function • Co-enzyme in protein metabolism – Trans-sulfuration • transfer of sulfur from methionine to serine to form cysteine – Conversion of cysteine to pyruvate • via cysteine desulfhydrase – Interconversion of glycine and serine – Decarboxylation of alpha-amino-beta-ketoadipic acid to delta- aminolevulinic acid
  • 67. PYRIDOXINE B6 Definition I Function • Co-enzyme in carbohydrate and fat metabolism – Conversion of Linoleic to Arachidonic acid – Cofactor in the activity of phosphorylase – Cofactor in the metabolism of unsaturated fatty acids and cholesterol – Synthesis of sphingolipids necessary for myelin formation
  • 68. PYRIDOXINE B6 Definition I Function • Enzymes : Amino transferases amino acid breakdown Glycogen phosphorylase glycogen breakdown Serine dehydratase feeding serine's breakdown product to gluconeogenesis Aminolevulinic acid synthase porphyrin synthesis
  • 69. PYRIDOXINE B6 Definition I Function • Essential for the maintenance of the integrity of : – Neuronal tissues – Production of anti-bodies – Bone development
  • 71. PYRIDOXINE B6 Deficiency • Clinical features: –Epileptiform seizures in infants –Pellagra-like skin lesions –GIT involvement- distention, vomiting , diarrhea –Anemia- hypochromic and microcytic
  • 72. PYRIDOXINE B6 Biochemistry • Important biochemical finding in Vitamin B6 deficiency: – Increased excretion of urinary oxalates – Mechanism: decreased conversion of glycine glyoxalate broken down to oxalic acid increased possibility of forming oxalate stones
  • 73. PANTOTHENIC ACID Definition • SYNONYMS: – “everywhere vitamin” – Filtrate factor • ROYAL JELLY
  • 74. PANTOTHENIC ACID Function • FUNCTION – Component of Coenzyme A • RDA: – Adults: 5-10 mg/day – Children: 4-5 mg/day – Infants: 1-2 mg/day
  • 75. PANTOTHENIC ACID Function Substrate Enzyme Product Pyruvate + CoASH Pyruvate DH complex Acetyl CoA α-ketoglutarate- CoASH Alpha-KG DH complex Succinyl CoA Fattyl acid + CoASH Thiokinase Acetyl-CoA Ketoacyl CoA + CoASH Thiolase Acyl CoA + Acetyl CoA Detoxification of benzoic acid Synthesis of bile salts
  • 76. PANTOTHENIC ACID Function • As Acetyl CoA Combines with oxaloacetic acid to form citric acid – first step in the Kreb’s cycle Combines with choline to form acetylcholine Combines with sulfonamide drugs to facilitate their excretion Precursor of cholesterol / steroid hormones Activation of some amino acids : valine, leucine and isoleucine Essential function in lipid metabolism
  • 77. PANTOTHENIC ACID Function • As Succiny CoA – Involved in heme biosynthesis • As Acyl Carrier Protein – Involved in fatty acid biosynthesis – Extra-mitochondrial lipogenesis
  • 79. PANTOTHENIC ACID Deficiency • Rare because: – Very widespread in natural foods – Most symptoms are vague and mimic those of other B vitamin deficiencies
  • 80. BIOTIN B7 Definition • SYNONYMS: – Vitamin B7; anti-egg white injury factor • CHARACTERISTICS: – Widely distributed in natural foods – From synthesis of bacteria - deficiency is caused by defects in utilization and not dietary – Long-term antibiotic treatment or excessive consumption of raw egg
  • 81. BIOTIN B7 Definition • AVIDIN – a protein in raw egg white which combines very tightly with biotin, preventing its absorption
  • 82. BIOTIN B7 Function • FUNCTION – Coenzymes for carboxylation reactions – Carrier of activated carbon dioxide • FOOD SOURCES – Almost all foods, liver, milk, egg yolk – 400 µg/day • DEFICIENCY – Uncommon – Raw egg avidin prevents absorption of Biotin
  • 84. Function CARBOXYLATION REACTIONS: BIOTIN B7 Substrate Enzyme Product Acetyl CoA Malonyl CoA acetyl CoA carboxylase Propionyl CoA Propionyl CoA carboxylase Methylmalonyl CoA Pyruvate pyruvate carboxylase Oxaloacetic acid
  • 86. BIOTIN B7 Deficiency • Man (rare) – Fine scaly skin desquamation (peeling) – Anorexia (lack or loss of appetite for food) – Nausea – Lassitude (lack of energy) – Muscle pains – Depression – Alopecia (baldness) – Graying of hair
  • 87. FOLIC ACID B9 Facts • SYNONYMS: – Vit B9, Folate, Folacin, PGA (Pteroylglutamic acid) • FUNCTION – One-Carbon metabolism – Essential in biosynthesis of thymidine, AA, and purine
  • 88. FOLIC ACID B9 Facts • FOOD SOURCES – Green leafy vegetables, liver, lima beans, whole grain cereals • DEFICIENCY – Growth failure – Megaloblastic anemia – Neural tube defects
  • 90. FOLIC ACID B9 Functions – Carrier of one-carbon group moieties. Form Formula Name Most reduced CH3 Methyl Intermediate CH2 Methylene Most oxidized CHO Formyl CHNH Formimino CH= methenyl
  • 91. FOLIC ACID B9 Forms Form Decription N5-methyl- THFA Most prevalent form transported in the blood N5, N10-methylene THFA Provides methyl group in the formation of thymidylate for DNA synthesis and erythrocyte formation N10 formy; THFA Provides C atom that becomes C2 of purine nucleus N5-formimino THFA Histidine catabolism N10-hydroyxymethyl THFA Thymine synthesis
  • 93. FOLIC ACID B9 Function 400 ug folate supplement
  • 94. FOLIC ACID B9 Deficiency Blood Cell Macrocytic Anemia- impaired production Blood Cell Microcytic Anemia Results when RBC are unable to divide…
  • 95.
  • 96. VITAMIN B12 Definition • SYNONYMS: – Antipernicious anemia vitamin – Cobalamin – Extrinsic Factor of Castle – Erythrocyte Maturation Factor • CHEMISTRY:
  • 97. VITAMIN B12 Chemistry • Consists of: 1. Corrin ring system - central portion of the molecule: similar to a porphyrin ring 2. 5,6-dimethylbenzimidazole riboside 3. Aminopropanolol 4. Propionic acid 5. Cobalt-occupies the center of the corrin ring system 1 5 43 2
  • 98. VITAMIN B12 Function • FUNCTION – Synthesis of methionine – Isomerization of methylmalonyl CoA
  • 99. VITAMIN B12 Function – Involved in the rearrangement of methylmalonyl CoA to succinyl CoA by methylmalonyl CoA isomerase •Involved in the transfer of a methyl group from methylTHFA to homocysteine to form methionine .
  • 100. VITAMIN B12 Sources ІDeficiency • FOOD SOURCES – Synthesized by microorganisms in the bacterial flora – Liver, whole milk, eggs – fresh shrimp, pork, chicken • RDA – Children: 2ug/day – Adults 3 ug/day – Pregnancy and lactation: 4 ug/day • DEFICIENCY – Abnormal fatty acid synthesis – Cell membrane defects/Neurological abnormalities – Pernicious anemia
  • 101. VITAMIN B12 Forms Forms Content Cobalamin Without cyanide Cyanocobalamin with cyanide group Hydroxocobalamin with hydroxyl group, more active in enzyme systems; retained longer in the body Methylcobalamin major form in the plasma 5’-deoxyadenosyl cobalamin readily binds to plasma-binding proteins
  • 102. VITAMIN B12 Deficiency • Causes: – Chronic dietary deficiency of vitamin B-12. – Poor absorption due to lack of intrinsic factor. • Presence of antibodies to the intrinsic factor in the gastric juice. • Lack of secretion of intrinsic factor (due to gastric mucosal cell atrophy or due to total gastrectomy. • Extensive resection of the small intestines. – Increased requirements as in pregnancy.
  • 103. VITAMIN B12 Deficiency • Clinical effects: “Pernicious Anemia” • No healthy RBC • Characterized by: – Megaloblastic or macrocytic anemia. – Lesions of the nervous system – Mucosal atrophy and inflammation of the tongue (glossitis), mouth (stomatitis) and pharynx (pharyngitis)
  • 104.
  • 105. ASCORBIC ACID (Vitamin C) Facts • Anti-scorbutic vitamin • Very sensitive to oxidation • Rapidly destroyed by alkalies • Freezing has no deleterious effect • Strong reducing agent • Drying vegetables usually results in loss of vitamin C.
  • 106. ASCORBIC ACID Facts • Sources: – Citrus fruits – Tomatoes – Strawberries – Green vegetables – Guava fruit – Green pepper • RDA: – Adults: 60 mg/day – Children: 40 mg/day
  • 108. ASCORBIC ACID Metabolic roles Hydroxylation of Proline and Lysine in collagen formation. Hydroxylation of tryptophan Synthesis of norephinephrine Tyrosine metabolism Hydroxylation of steroids in the adrenal cortex Serves as a reductant of ferric to ferrous ion Involved in the conversion of folic acid to active THFA Involved in the hydroxylationof cholesterol to cholic acid Acts as regulator of cholesterol metabolism
  • 109. ASCORBIC ACID Function • Major function of vitamin C – coenzyme in the formation of tissue collagen or intracellular cement substance
  • 110. ASCORBIC ACID Function • Major function of vitamin C – coenzyme in the formation of tissue collagen or intracellular cement substance
  • 111. ASCORBIC ACID Deficiency • Spongy gums • Poor wound healing
  • 112. ASCORBIC ACID Deficiency • Splinter hemorrhages in nails • subcutaneous hemorrhages
  • 113. ASCORBIC ACID Deficiency • swelling at the ends of long bones
  • 114. FAT-SOLUBLE VITAMINS Structure • Vitamin A • Vitamin D • Vitamin K • Vitamin E retinol, B-carotenes cholecalciferol phylloquinones, menaquinones tocopherols
  • 115. VITAMIN A Retinol Structure • Retinol and retinoic acid – act like steroid hormones • Retinalehyde is a component of Rhodposin • Retinoic acid participates in glycoprotein synthesis
  • 116. VITAMIN A Retinol Function • Provitamin - β carotene • FUNCTION – Maintenance of reproduction – Maintenance of vision – Promotion of growth – Gene expression – Treatment of psoriasis, acne, cancers • FOOD SOURCES – Liver, kidney, cream, butter, egg yolk – Yellow and dark green vegetables
  • 117.    Dietary Vitamin A, from animal sources is available in the form of Retinyl esters, which is hydrolyzed to retinol and fatty acid by pancreatic hydrolases The absorption of retinol requires the presence of bile salts In the intestinal cells, retinol is esterified back and secreted with chylomicrons
  • 118. • The liver contains approximately 90% of the vitamin A reserves and secretes vitamin A in the form of retinol, which is bound to retinol- binding protein. • • The retinol-binding protein complex interacts with a second protein, Transthyretin. This trimolecular complex functions to prevent vitamin A from being filtered by the kidney glomerulus, to protect the body against the toxicity of retinol and to allow retinol to be taken up by specific cell-surface receptors that recognize retinol-binding protein.
  • 119. • In the retina, retinaldehyde functions as the prosthetic group of the light-sensitive opsin proteins, forming Rhodopsin (in rods) and iodopsin (in cones). • • • Any one cone cell contains only one type of opsin, and is sensitive to only one color. The absorption of light by Rhodopsin causes isomerization of the retinaldehyde from 11-cis to all-trans, and a conformational change in opsin. This results in the release of retinaldehyde from the protein, and the initiation of a nerve impulse.
  • 120.   The formation of the initial excited form of Rhodopsin, bathorhodopsin, occurs within pico-seconds of illumination. There are then a series of conformational changes leading to the formation of metarhodopsin II, which initiates a guanine nucleotide amplification cascade and then a nerve impulse.
  • 121.  The final step is hydrolysis to release all- trans-retinaldehyde and opsin.   The key to initiation of the visual cycle is the availability of 11-cis-retinaldehyde, and hence vitamin A. In deficiency, both the time taken to adapt to darkness and the ability to see in poor light are impaired.
  • 122. VITAMIN D Facts • FUNCTION – 1,25-dihydrocholecalciferol- a steroid hormone – Stimulates gene expression or repress gene transcription – Regulates plasma levels of calcium and phosphorus
  • 123. Vitamin D Synthesis •Vitamin D in reality is a hormone and is a metabolic product of the cholesterol biosynthetic pathway •Vitamin D3, a cholecalciferol is synthesized de novo by the exposure of skin to sunlight that converts 7- dehydrocholesterol to vitamin D3 •Vitamin D3 is then converted in liver, to 25- hydroxycholecalciferol (25-OH- D3) by the enzyme 25- hydroxylase - still an inactive form •25-OH- D3 is the blood test used to assess adequacy of vitamin D stores in the body •In the kidney, renal 1 α-hydroxylase hydrolyses 25-OH- D3 to form 1,25-dihydroxycholecalciferol (1,25-[OH]2- D3) – the biologically active form (PTH stimulates this enzyme)
  • 124. Vitamin D from diet Vitamin D is relatively rare in most typical foods. The only common dietary source of vitamin D are multivitamins , supplements and vitamin D fortified milk. Cod liver oil is also a source of vitamin D
  • 126. The actions of Vitamin D 1. Enhances calcium absorption from the intestine 2. Facilitates calcium reabsorption in the kidney 3. Increases bone calcification and mineralization 4. In excess, mobilizes bone calcium and phosphate.
  • 127. VITAMIN D Action Response to low plasma calcium
  • 128. VITAMIN D Deficiency • DEFICIENCY – Rickets – Osteomalacia (demineralization of bone) • TOXICITY – Most toxic of all vitamins – Deposition of calcium in organs and arteries, kidney stones
  • 129. Vitamin K  Three compounds have the biological activityof vitamin K  Phylloquinone (Vitamin K1), the normal dietary source, found in green vegetables  Menaquinones (vitamin K2), synthesized by intestinal bacteria,with differing lengths of side chain;  and Menadione and menadiol diacetate, synthetic compounds thatcan be metabolized tophylloquinone.
  • 130. Dietary Sources  Green leafyvegetables such as kaleand spinach,  Margarine and liver.  Vegetableoilsand particularlyolive, canola, and soybean oils.  Some amount is contributed byintestinal bacteria 6
  • 131. Absorption, Transportation and Storage  Absorption takes place in small intestine in the presence of bile salts.  The transportation from intestineis carried out throughchylomicrons.  Storage occurs in liver and from liver transportation to peripheral cells is carried out bound with betalipoproteins (VLDL). 1 3
  • 132. Recommended daily allowance (RDA)  The averagedaily allowance is 50-120 mcg/day.  Requirement increases in –  Liverdisorders  Patients on prolonged antibiotictherapy, and Orlistat (weight loss medication)
  • 133. Functions of Vitamin K Coagulation Bone Synthesis Prevention of atherosclerosis 1 3
  • 134. Vitamin K deficiency Vitamin K deficienc y Dietary deficiency Fat malabsorp tion Surgical interventi ons of intestine Chronic liver diseases Prolonged intake of antibiotics
  • 135.  Chemical nature:  Vitamin E is chemically known as tocopherol (Greek: tocos=childbirth, piro=to bear and ol=alcohol) • An alcohol was capable to prevent reproductive failure in animals • Hence it is known as anti-sterility vitamin • Chemistry: • Vitamin E is the name given to group of tocopherols and tocotrienols
  • 136.  About 8 tocopherols have been identified  Alpha- tocopherol is most active  The tocopherols are derivatives of 6-hydroxy chromane (tocol) ring with isoprenoid side chain  The antioxidant property is due to the chromane ring
  • 137. ABSORPTION  Vitamin E is absorbed along with fat in the upper small intestine  Mechanism: Vitamin E combines with Bile salts (micelles) to form mixed micelle and taken up by the mucosal cell  In the mucosal cell, it is incorporated into chylomicrons
  • 138. Biochemical functions 1.Vitamin E is essential for membrane structure and integrity of the cell, hence it is membrane antioxident 2. It prevents the peroxidation of PUFA 3.It protects the RBC from hemolysis by oxidizing agents (H2O2) 4.It is associated with reproductive function and prevents sterility
  • 139. 5.Vitamin E preserves and maintains germinal epithelium of gonads for proper reproductive function 6.It increases the synthesis of heme by enhancing the activity of enzyme – δ aminolevulinic acid (ALA) synthase and ALAdehydratase 7. It is required for cellular respiration –through ETC (Stabilize coenzyme Q) 8. Vitamin E prevents the oxidation of Vitamin A and carotenes 9. Vitamin E prevents oxidation of LDL, Oxidized LDL promotes heart diseases
  • 140.  Males  Females  Pregnancy  Lactation -10 mg/day - 8 mg/day - 10 mg/day - 12 mg/day  15 mg of vitamin E is equivalent to 33 IU  Pharmacological dose is 200-400 IU/day  Sources:  Rich sources are vegetable oils  Includes germ oil, sunflower oil, corn oil and margarine
  • 141. VITAMINS Definition I Function VITAMIN FUNCTIONS DEFICIENCY DISEASE A Retinol, β-carotene Visual pigments in the retina; regulation of gene expression and cell differentiation; Antioxidant Night blindness, xerophthalmia; keratinization of skin D Calciferol Maintenance of calcium balance; enhances intestinal absorption of Ca++ and mobilized biomineral Rickets = poor mineralization of bones; Osteomalacia = bone demineralization E Tocopherols Tocotrienols Antioxidant, especially incell membranes Extremely rare - serious neurologic dysfunction K Phylloquinone Menaquinone Coenzyme in formation of γ- carboxyglutamate in enzymes of blood clotting and bonematrix Impaired blood clotting, hemorrhagic disease
  • 142. VITAMINS Definition I Function VITAMIN FUNCTIONS DEFICIENCY DISEASE B1 Thiamin Coenzyme in pyruvate and α- ketoglutarate DH, and transketolase; poorly defined function in nerve conduction Peripheral nerve damage (beriberi) or CNS lesions (Wernicke-Korsakoff syndrome) B2 Riboflavin Coenzyme in redox reactions; prosthetic group of flavoproteins Lesions of corner of mouth, lips and tongue, seborrheic dermatitis B3 Niacin Nicotinic acid Nicotinamide Coenzyme in redox reactions; functional part of NAD and NADP Pellagra- photosensitive dermatitis, depressive psychosis Energy-Releasing
  • 143. VITAMINS Definition I Function Energy-Releasing VITAMIN FUNCTIONS DEFICIENCY DISEASE Pantothenic Acid Functional part of CoA and acyl carrier protein: fatty acid synthesis and metabolism Biotin Coenzyme in carboxylation reactions in gluconeogenesis and fatty acid synthesis Impaired fat and CHO metabolism, dermatitis
  • 144. VITAMINS Definition I Function VITAMIN FUNCTIONS DEFICIENCY DISEASE Folic acid Coenzyme in transfer of one- carbon fragments Megaloblastic anemia B12 Cobalamin Coenzyme in transfer of one- carbon fragments and metabolism of folic acid Pernicious anemia = megaloblastic anemia with degeneration of the spinal cord Hematopoeitic
  • 145. VITAMINS Definition I Function VITAMIN FUNCTIONS DEFICIENCY DISEASE B6 Pyridoxine Pyridoxal Pyridoxamine Coenzyme in transamination & decarboxylation of AA and glycogen phosphorylase; role in steroid hormone action Disorders of AA metabolism, convulsions C Ascorbic Acid Coenzyme in hydroxylation of proline and lysine in collagen synthesis; antioxidant; enhances iron absorption Scurvy- impaired wound healing, loss of dental cement, subcutaneous hemorrhage Other functions