3. Vitamin = Vit + Amine
= Health + NH2
Vitamins
are
ACCESSORY FOOD FACTORS NECESSARY TO MAINTAIN LIFE
They are organic compounds have the following characters
1- Essential for health and growth.
2- Can not be formed in the body (must be taken in food ).
3- Needed in very small amounts.
4- Act as co-catalysts (coenzymes)
5- Not oxidized to give energy.
6- Not enter in tissue structure.
4. Vitagens = E.A.A. & E.F.A.
Which have the following characters:
1- Oxidized to give energy.
2- Needed in big amounts.
3- Enter in tissue structure
Vitamers =more than one chemical form of vitamins
e.g. Vitamin D have Vitamin D2 Vitamin D3
Vitamin E have 6 VITAMERS (Alfa, Bete,
Gamma, Delta, Eta, Zeta)
Provitamin = Vitamin Precursor
Carotenes = Provitamin A
7 Dehydrocholesterol = Pro Vitamin D3
Ergosterol = Pro Vitamin D2
5. Vitamins
Vitamins are organic molecules that function in
a wide variety of capacities within the body.
The most prominent function is as cofactors for
enzymatic reactions.
The distinguishing feature of the vitamins is that
they generally cannot be synthesized by
mammalian cells and, therefore, must be supplied
in the diet.
The vitamins are of two distinct
types:
7. Fat Soluble Vitamins
A D E K
Vitamin A = Anti- xerophthalmia
= Anti night blindness Vitamin
Vitamin D = Anti rickets Vitamin
Vitamin E = Anti-Oxidant Vitamin
= Anti Rat Sterility Vitamin
Vitamin K = Anti-Hemorrhagic Vitamin
8. Water Soluble
Vitamins
1 – Vitamin C = L-Ascorbic Acid
= Antiscurvy
2 – B complex Vitamins (12)
5 + 1 + 3 + 3
9. (5)
Vitamin B1= Thiamine= Anti beri beri= Anti neurotic vita
Vitamin B2 = Riboflavin = Lactoflavin
Vitamin B3 = Niacin = Nicotinic Acid = P.P.F.
Vitamin B6 = Pyridoxine = Pyridoxal = Pyridoxamine
Vitamin B12 = Cobalamine = Anti pernicious Anemia Vita
(1)
Vitamin H = Biotin = Anti raw egg white injury factor
(3)
Pantothenic Acid = Vitamin B5
Folic Acid = Petroyl Glutamic Acid
PABA = Para Amino Benzoic Acid
(3)
Choline - Inositol - Lipoic acid
10. Water Soluble Vitamins
1 – Vitamin C = L-Ascorbic Acid = Antiscurvy
2- B complex Vitamins
- Thiamin (B1), B1 Deficiency and Disease
- Riboflavin (B2), B2 Deficiency and Disease
- Niacin (B3), B3 Deficiency and Disease
- Pantothenic Acid (B5)
- Pyridoxal, Pyridoxamine, Pyridoxine (B6)
- Biotin
- Cobalamin (B12), B12 Deficiency and Disease
- Folic Acid, Folate Deficiency and Disease
11. Deference 2 types of vitamins
Non polar and H2O insoluble.
1. Polar and water soluble
May be synthesized in plants
2. Synthesized in plants except B12
Main source is animals
3. Main source is plants
Usually stored in body
4. Not stored except vit. B12
All contain isoprenoid units
5. Do not contain isoprenoid
units
Do not form coenzyme except
vitamin K
6. All act as coenzymes except
vitamin C
Absorbed with lipids into lymph
7. Directly absorbed into blood
Can accumulate and cause
hypervitaminosis (toxicity)
8. Rarely accumulated usually
not toxic
Excreted in bile and feces
9. Excreted in urine
Deficiencies can occur but rare
10. Deficiencies are common
Individual vitamin deficiency
occurs
11. Deficiency occurs as a group
14. Dietary Sources of Vitamin A
Animal foods: Liver, fish oil, kidney, egg yolk, Milk, butter
Plants: Carrots, dark green leafy vegetables (beta-
carotene), spinach, broccoli, sweet potatoes
RDA: 700-900 mcg
1mcg of retinol=3.33 IU of vit. A
15. Beta carotenes (food)
splitting by Di-oxygenase
(1) (Forms of Vit. A)
2 Molecules of Retinal = Retinene = Aldehyde Form
Reduced NADP
Retinal Reductase (intestinal)
Oxidized NADP (2-A)
2 Molecules of Retinol = Vit. A1 = Alcohol Form
Salted water fish (2-B)
There is also saline water fish (3-dehydro retinol ) = Vit. A2
(3)
Last form of Vit. A is Vit. A acid = Retinoic acid
17. Metabolism of Vitamin A
Absorption: proximal small bowel
Transported by chylomicrons (retinyl ester + retinol)
Stored in liver (esters + CRBP [cellular retinol binding protein])
Stellate cells 80-90%
Hepatocytes 10-20%
Released into plasma as retinol + RBP (bound to prealbumin)
From diet: 50% stored in the liver
20% excreted in feces (from bile)
17% excreted in urine
10% not absorbed
3% CO2
18. Visual cycle
Rhodopsin
Dim Light Bright Light
11 Cis Retinal Opsine All Trans Retinal
Reduced NAD
Oxidized NAD
11 Cis Retinol All Trans Retinol
Retinal cell
Blood
Liver Cells
11 Cis Retinol Retinol Isomerase All Trans Retinol
Conversion of 11 Cis Retinal into All Trans Retinal leads to
Conformational changes in membrane of Rods cells leads
to production of Ca ion Channels (Rapid influx of Ca ion)
which trigger nerve impulse to be allowed to be received by the
brain.
20. Biochemical Roles of Vitamin A
1- In Vision (al form) through formation of Rhodopsin &
Iodopsin, ALSO Regeneration & breakdown of these
pigments
in visual cycle during exposure to bright and dim light
throughout daily life.
2- In Reproduction (al, ol forms).
3- In Growth (acid form).
4- In Differention & maintenance of healthy epithelium (acid
form). normal mucous secretion.
5- Hormonal Like Activity (ol form). Which have role in
regulation of gene expression (Protein Biosynthesis).
6- In Glycoprotein Formation (acid form). e.g. receptors.
have anticancerous & other biological properties.
21. Vitamin A Deficiency
- Delay in dark adaptation (early sign)
- Loss of night vision (Nyctalopia)
- Xeroderma (Goose skin), rough & keratinized skin.
- Exophthalmia (rough & keratinized Conjunctiva)
- Keratomalacia (rough & keratinized Cornea)
- Corneal Opacity, Soften & Perforation (loss of vision)
- Urinary tract infections & stone formation
- Respiratory tract infections.
- Growth Retardation.
22. Hypervitaminosis A
(Vitamin A toxicity)
- Periosteal thicking of long bones.
- Painful joints
- Loss of hair
- Irritability
- Loss of appetite
- Weight loss
- Night sweats
- Headache
23. Vitamin D (Anti rickets Vitamin)
Vitamin D is a steroid hormone that functions to regulate
specific gene expression following interaction with its
intracellular receptor
The biologically active form is the hormone 1,25-dihydroxy vitamin
D3 (1,25-(OH)2D3, [1,25 dihydroxy chol calceferol ] also
termed calcitriol).
Calcitriol functions primarily to regulate calcium and
phosphorous homeostasis.
Ergosterol (Plant ) Vitamin D2
24. Sources of Vitamin D
Vitamin D is found naturally in very few foods
Dietary source: fatty fish (mackerel, salmon, sardines), cod-liver oil,
eggs yolks
Fortified milk (vitamin D2/D3), cereals and bread products, orange juice
Infant formula is fortified with vit. D (400 IU per quart)
25. 7-Dehydrocholesterol (Animal ) Vitamin D3
Active calcitriol is derived from ergosterol (produced
in plants) and from 7-dehydrocholesterol (produced
in the skin).
Ergocalciferol (vitamin D2) is formed by UV irradiation
of ergosterol.
In the skin 7-dehydrocholesterol is converted to
cholecalciferol (vitamin D3) following UV irradiation.
28. Vitamin D Metabolism
Vitamin D itself not need digestion
Absorption through Micelle formation.
Carried by specific globulins to be transported to liver.
In liver: (First hydroxylation) There is oxidation by D3-25-
hydroxylase (liver microsomal enz.) to form 25 hydroxy
D3 (Calcifediol ) which can stored in liver if excess or
reabsorbed from intestine through enterohepatic circulation to go to
general circulation or excreted with bile.
29. Final Activation
From general circulation go to Kidney,
Bone, Placenta where there is another
enzyme called D3-1-hydroxylase
(Second hydroxylation) (mitochondrial
enz.) regulated by Parathormone &
serum phosphorous to form 1-25 di-
hydroxy D3 (Calcitriol).
There is another enzyme called D3-24-
hydroxylase (Kidney, Cartilage,
Placenta present in mitochondria) to
form 24-25 di-hydroxy D3 .
30. There are 2 Active forms of Vitamin D3
* 1,25 di-hydroxy D3 (Calcitriol)
* 24-25 di-hydroxy D3
Both forms have nearly equal plasma concentrations
when Ca++ serum level is normal.
During Hypo Ca ; parathormone hormone can
1- Increase levels of 1,25 DHCC
2- Decrease levels of 24,25 DHCC
During Hypo P ; parathormone hormone can
Increase levels of 1,25 DHCC
Both Hypo Ca and Hypo P
can increase activity of D3-1-25-hydroxylase
31. Biochemical Role
of Calcitriol (1,25 DHCC)
1, 25, Dihydroxy Cholecalceferol
1- Increase Intestinal Absorption of Ca & P.
2- Enhance Ca mobilization (through increase carrier
protein synthesis) from kidney & bone.
3- Increase synthesis of Osteocalcin (Vit. K dependent Ca
binding protein= bone protein contain gamma carboxy
glutamate molecules)
32. Biochemical Role
of 24,25 DHCC
24, 25, Dihydroxy Cholecalceferol
1- Increase Intestinal Absorption of Ca++.
2- Decrease serum concentration of both Ca & P.
3- Promotes normal bone mobilization.
4- Promotes synthesis of hydroxy apatite crystals .
major form of Ca in miniralized bone & cartilage.
33. Mechanism of
action of DHCC
Inside intestinal Epithelial cell 1,25 DHCC bound
with specific cytoplasmic receptor molecule.
1,25 DHCC-receptor complex
is translocated into nucleus where
it can increase synthesis of
intestinal Ca binding protein(CBP)
necessary for intestinal Ca absorption through
regulation of Gene Expression.
34. 25-hydroxyvitamin D3 1,25-dihydroxyvitamin D3
Calcitriol functions in concert with parathyroid hormone
(PTH) and calcitonin to regulate serum calcium and
phosphorous levels.
PTH is released in response to low serum calcium and
induces the production of calcitriol. In contrast,
reduced levels of PTH stimulate synthesis of the
inactive 24,25-(OH)2D3.
35. Deficiency of Vitamin D
1- In Adult: Osteomalacia (Bone deformities,
Low Blood P & Ca) due to multiple pregnancies with
bad dietary habits, usually occurred with poor ignorant
women.
2- In Young Infants: Rickets which is manifested by
1- Delayed teething, sitting, standing, walking.
2- Dental caries (common)
3- Bone soften and Deformities e.g.
- Boxy skull - Bow leg - Knock knee
- Pigeon chest - Contracted pelvis
36. 4- Blood chemistry changes:
- Low blood phosphorous.
- Normal blood Ca.
- High blood alkaline phosphatase.
37. Vitamin D Deficiency
Children
Rickets
Failure of bone mineralization in infants and
children
Delayed closure of the fontanels (soft spots) in
the skull
Deformed rib cage in infants (Herison sulcus)
Seizures from hypocalcaemia
38. Hypervitaminosis D
(Vitamin D toxicity)
- Anorexia
- Nausea
- Vomiting
- Weakness
- Polyuria
- Abnormal cacification of tissues including lung
& kidneys
39. Vitamin E
(Tocopherols)
Toco= child birth phero= to carry ol= alcohol
Derivatives of Tocol nucleus
6 Vitamers
Alpha
Beta
Gamma
Delta
Eta
Zeta
40. Vitamin E
a-Tocopherol
Vitamin E is a mixture of several related compounds known as
tocopherols. The a-tocopherol molecule is the most potent
of the tocopherols.
Vitamin E is absorbed from the intestines packaged in
chylomicrons. It is delivered to the tissues via chylomicron
transport and then to the liver through chylomicron remnant
uptake. The liver can export vitamin E in VLDLs. due to its
lipophilic nature.
41. Vitamin E
Suboptimal intake of vit. E is relatively common in the U.S.
Food sources: vegetable oils (olive, sunflower, safflower),
nuts and seeds, rice, whole grains, green leafy vegetables
Vit. E is destroyed by heat
The RDA for vitamin E
Women 8 mg/d
Men 10 mg/d
42. Metabolism of Vitamin E
Intestine: Pancreatic esterases break down tocopheryl-ester
bonds between vitamin E and fatty acids
Liver: alpha-tocopherol is packaged within VLDL molecules
Blood: Transported by α-tocopherol transfer protein
Vit.E : is stored in adipose tissue (90%)
43. Biochemical role of Vitamin E
1- Anti-Oxidant; Tochopherols prevent
destruction of PUFA & ALSO Vitamin A.
Tochopherols inhibit lung tissue damage
occurred by air oxidants.
2- Vitamin E with Reduced Glutathione (GSH)
in the presence of Selenium containing
glutathione peroxidase enzyme are very
importan defense mechanisms against
toxic peroxides produced during cellular
metabolism.
44. 3- Resistance against heamolysis of
RBCs
4- Tocopherols with Selenium (trace element
called factor 3) prevent acute
hepatic necrosis occurred in animals fed on
diet low in proteins & sulphur containing
amino acids
5- In Rats deficiency causes sterility of male
and death of fetus in pregnant females.
6- In many animals can cause muscular
dystrophy.
45. Clinical significance of Vitamin E Deficiency
No major disease states have been found to be associated with
vitamin E deficiency due to adequate levels in the average diet.
The major symptom of vitamin E deficiency in humans is
an increase in red blood cell fragility.
Since vitamin E is absorbed from the intestines in chylomicrons,
any fat malabsorption diseases can lead to deficiencies in
vitamin E intake.
Neurological disorders have been associated with vitamin E
deficiencies associated with fat malabsorptive disorders.
46. Increased intake of vitamin E is
recommended in premature infants fed
formulas that are low in the vitamin as well as
in persons consuming a diet high in
polyunsaturated fatty acids.
Polyunsaturated fatty acids tend to form
free radicals upon exposure to oxygen
and this may lead to an increased risk of
certain cancers.
47. Vitamin K
Coagulation Vitamin
Derivatives from Naphthoqinone Ring
There are 3 forms according to differences in side chain R
1- Vitamin K1 (Phylloqinone)
2- Vitamin K2 (Menaoqinone)
3- Vitamin K3 (Menadione) = Water soluble Vit
has no side chain. Inside the body the side chain R (Alkyl
side chain) is added. Not need bile salts for absorption and
goes directly to blood.
48. Vitamin K
The K vitamins exist naturally as K1 (phylloquinone) in
green vegetables and K2 (menaquinone) produced by
intestinal bacteria and K3 is synthetic menadione.
When administered, vitamin K3 is alkylated to one of
the vitamin K2 forms of menaquinone.
Vitamin K1 Vitamin K2 Vitamin K3
"n" can be 6, 7 or 9 isoprenoid groups
49. Sources
- Vitamin K1: Green leafy vegetables e.g. spinach,
Alpha
alpha, vegetable oils, Wheat bran.
- Vitamin K2: produced by intestinal bacteria (very important
source of Vitamin K2)
- Vitamin K3: Synthetic by pharmaceutical companies
50. Biochemical ROLE
Vitamin K have a principal roll in post-translational
processing (modification) of some proteins i.e. needed
for carboxylation of certain amino acid residues of some proteins
in gamma position (activation) producing gamma carboxy
glutamate which is important in
- Activation of blood clotting factors No 2,7,9,10
containing several molecules of gamma carboxy glutamate
- Osteocalcin & many other proteins in plasma, lung,
spleen, placenta
51. Vitamin K Cycle in liver cells
Quinone Form
(1)
Reduced NADP
Epoxide Reductase
Oxidized NADP
(2) Mono oxygenase (3)
Epoxide Form Hydroquinone Form
Epoxide Reductase inhibit coumarin compounds (e.g. Warfarine
drug Anticoagulant)
N.B. Warfarine drug is synthetic analogue of Vitamin K
& ACT as anticoagulant
Dicumarol is natural anticoagulant & natural
analogue.
Vitamin K Deficiency
Prolonged bleeding & clotting times and
Bleeding can occur from minor injury
52. Metabolism of Vitamin K
Vitamin K is absorbed in the distal small intestine
Dietary vitamin K is protein-bound and requires liberation by proteolysis
(pancreatic enzymes)
Bile salts solubilize vitamin K into micelles for absorption into
chylomicrons (transport via portal circulation to the liver)
Microorganisms of the colon and distal ileum can synthesize
absorbable vitamin K
53. Vitamin K Deficiency
Occur in; (Persons susceptible to deficiency)
1-Newely born infant due to sterility of their large
intestine.
2-Long treatment with intestinal antibiotics e.g.
tetracycline.
3-Liver diseases due to disturbed vit. K cycle and no usage
of vit. K for activation of prothrombin & other clotting
factors.
4- Obstrructive Jaundice due to defective absorption of
vit. K as in bile salts deficiency.
5- Long treatment with Dicumarol (natural anticoagulant
=natural analogue of epoxide form of vitamin k)
54. Water Soluble Vitamins
(1) - Vitamin C
(2) - Vitamin B complex (12 members)
(5)
Vitamin B1= Thiamine= Anti beri beri= Anti neurotic vita
Vitamin B2 = Riboflavin = Lactoflavin
Vitamin B3 = Niacin = Nicotinic Acid = A.P.F.
Vitamin B6 = Pyridoxine = Pyridoxal = Pyridoxamine
Vitamin B12= Cobalamine=Anti pernicious Anemia
(1)
Vitamin H = Biotin = Anti raw egg white injury
factor
(3)
Pantothenic Acid = Vitamin B5
Folic Acid = Petroyl Glutamic Acid
PABA = Para Amino Benzoic Acid
(3)
Choline - Inositol - Lipoic acid
55. Vitamin C
(L-Ascorbic Acid) = Antiscorbutic Vitamin
Derivative from sugar acid called L- Gulonic acid (aldonic acid
of aldo sugar called L- Gulose).
L- gluconolactone oxidase
L- Gulonic acid L- Ascorbic acid
This enzyme absent in humans (occurred in lower animals)
Vitamin C IS Antioxidant vitamin such as Vitamin E & β-carotenes
Water soluble, heat labile, have high reducing power
Sources;
1- Guava and Citrus fruits e.g. Lemons, orange etc.
2- Fresh green vegetables e.g. Lettuce, watercress, etc.
Milk is a poor source of vit. C.
56. Vitamin C
ASCORBIC ACID
Dietary source:
Citrus fruit
Fresh fruit
Vegetables
Absorption: distal small intestine
Intake up to 100 mg/d - 100% absorbed
Intake >1000 mg/d - <50% absorbed
Excess of vit. C removed by kidneys
57. VITAMIN C
Functions: Antioxidant (biologic reductant)
provides electrons to reduce molecular O2
Involved in iron/copper reactions
RDA:
Adult 75-90 mg/d
Elderly 125 mg/d
Smokers - requirement by ~ 40%
58. Biochemical role of Vitamin C
1- Needed for maturation of collagen fibers & matrix of
connective tissues through hydroxylation of proline & lysine
residues (Post-translational Modifications)
Precollagen Collagen
2- In decreased capillary permeability and fragility.
3- In Carnitine formation (needed for F.A. catabolism) through
hydroxylation of betaine (Trimethyl-amino) of butyric acid
4- Involved in tyrosine oxidation (catabolism)
5- Reduction of folic acid to folinic acid.
6- Needed for iron absorption through reduction of ferric iron
to ferrous state.
7- Essential for general growth, formation of bone, teeth &
blood cells.
59. Vitamin C Deficiency
(Scurvy)
1- Hemorrhages - under skin
- from mucous membranes
- in internal organs
2- Gums become swollen and bleeds easily.
3- Teeth becomes loose and may fall.
4- Poor wounds healings.
5- Easy bone fractures
60. Vitamin C Deficiency
Scurvy
Described in Egyptian, Greek, and Roman
literature
A major cause of morbidity and death in the US
during Civil War and the California gold rush
Ascorbate is an essential nutrient derived from
the diet
Scurvy develops 2-3 months with diet deficient
in ascorbic acid
61. Vitamin C Deficiency
Groups at Risk
Poor dietary intake
Severely malnourished individuals
Drug and alcohol abusers
Poverty
Elderly, institutionalized pts.
62. Symptoms of Vitamin C Deficiency
Swollen and bleeding gums
Loosened teeth
Arthralgias and joint effusions
Lower extremities weakness
Petechiae and periungual hemorrhage
Ecchymoses
Corkscrew hair
Slow wound healing
Anaemia
Death
63. (1) Thiamin (vitamin B1)
Thiamin structure
Thiamin is also known as vitamin B1 .
Thiamin is derived from a substituted pyrimidine and a
thiazole which are coupled by a methylene bridge.
Thiamin is rapidly converted to its active form, thiamin
pyrophosphate, TPP, in the brain and liver by a specific
enzymes, thiamin di-phospho transferase.
Thiamin pyrophosphate (TPP)
64. Vitamin B1 (Thiamine)
Thiamine was named "the antiberiberi factor“ (1926)
Absorption: jejunum/ileum
Biologic half-life: ~10-20 days
Limited tissue storage
Continuous supplementation is required
65. Thiamine
Functions: Cofactor for enzymes in AA and CHO
metabolism
Dietary sources: yeast, legumes, rice, cereals
RDI: 1.2-1.5 mg/d; parenteral dose - 3 mg/d
Thiamine requirement:
based on the total caloric intake
0.5 mg of vit. B1 daily /1000 Kcal for adults
66. TPP is necessary as a cofactor (Co- carboxylase) for
the
pyruvate and a- ketoglutarate dehydrogenase catalyzed
reactions (Oxidative decarboxylation reactions which
need 5 coenzymes; TPP, Lipoic acid, NAD, FAD, CoA sH),
ACT as hydrogen carriers
pyruvate dehydrogenase
Pyruvate Acetyl Co A
a- ketoglutarate dehydrogenase
a- ketoglutarate Succinyl Co A
as well as the transketolase catalyze reactions of the
pentose phosphate pathway.
Both reactions are needed in intermediary metabolism
especially CHO metabolism, so impairment of glucose
67. Individuals at Risk for
Thiamine Deficiency
Alcoholics:
Calorie-protein poor diet
Severe malnutrition
Malabsorption
Gastric bypass
Chronic renal failure on HD
Prolonged febrile illness
69. Beriberi
Adult beriberi:
Dry beriberi: distal symmetrical peripheral neuropathy of the
extremities (sensory and motor impairment)
Wet beriberi: neuropathy / cardiac involvement – high output CHF
(cardiomegaly, cardiomyopathy, tachycardia, pitting peripheral
oedema)
Other symptoms: anorexia, weight loss, confusion, muscle wasting,
weakness
Infantile beriberi (infants, 2-3 months of age)
70. Wernicke-Korsakoff Syndrome
Almost exclusively described in chronic alcoholics
Wernicke’s encephalopathy: horizontal nystagmus, ophthalmoplegia,
gait ataxia, confusion, weakness
Korsakoff's psychosis
Impaired short-term memory and confabulation
genetic predisposition - impaired synthesis of erythrocyte
transketolase
71. Thiamin deficiency
Beri – Beri disease (2 Types)
Occur due to poor food intake, alcoholics.
1- Dry beri-beri due to atrophy of peripheral nerves
which causes numbness, tingling, loss of sensation &
paralysis.
2- Wet beri-beri, manifested by heart failure,
edema.
the levels of pyruvate, pentose sugars & alpha keto
acids of branched chain amino acids e.g. leucine,
isoleucine and valine are increased.
72. A deficiency in thiamin intake leads to a
severely reduced capacity of cells to
generate energy as a result of its role in
PREVIOUS reactions.
The dietary requirement for thiamin is
proportional to the caloric intake of the
diet and ranges from 1.0 - 1.5 mg / day
for normal adults.
73. (2) Riboflavin (vitamin B2 ) Lactoflavin
Riboflavin
structure
=
Flavin +
D- ribitol
Riboflavin is the precursor for the coenzymes, flavin
mononucleotide (FMN) and flavin adenine dinucleotide (FAD).
The enzymes that require FMN or FAD as cofactors are termed
flavoproteins.
Several flavoproteins also contain metal ions and are termed
metalloflavoproteins.
Both classes of enzymes are involved in a wide range of redox
reactions, e.g. succinate dehydrogenase and xanthine oxidase..
75. VITAMIN B2 (RIBOFLAVIN)
STORED IN THE BODY AS FLAVOPROTEINS
POORLY SOLUBLE IN WATER
FUNCTIONS:
INVOLVED IN CELLULAR METABOLISM, OXIDATION -
REDUCTION REACTIONS; ELECTRON TRANSPORTER
ESSENTIAL COMPONENT OF COENZYMES
FLAVIN MONONUCLEOTIDE (FMN)
FLAVIN-ADENINE DINUCLEOTIDE (FAD)
78. Biochemical role of Riboflavin
During absorption, riboflavin is phosphorylated in presence of
ATP & FLAVOKINASE enzyme to form FMN, FAD which act as
hydrogen carriers.
Enzymes (flavoproteins) that use FMN as coenzyme:
1- L- amino acid dehydrogenase.
Enzymes (flavoproteins) that use FAD as coenzyme:
1- Pyruvate dehydrogenase (CHO metabolism).
2- Glycine Oxidase (Protein metabolism).
3- Acyl Co-A dehydrogenase (lipid metabolism).
4. Xanthine Oxidase (Nucleotide metabolism).
79. Clinical Significances of Flavin Deficiency
Riboflavin deficiencies are rare disease due to the
presence of adequate amounts of the vitamin in eggs,
milk, meat and cereals in many countries.
Riboflavin deficiency is often seen in chronic alcoholics
due to their poor dietetic habits.
Symptoms associated with riboflavin
deficiency include, glossitis, seborrheic dermatitis,
angular stomatitis, cheilosis and photophobia.
Riboflavin decomposes when exposed to visible light. This
characteristic can lead to riboflavin deficiencies in
newborns treated for hyperbilirubinemia by
phototherapy.
80. MANIFESTATIONS OF VIT. B2
DEFICIENCY
ANGULAR STOMATITIS
CHEILOSIS
GLOSSITIS
SORE THROAT
SEBORRHEIC DERMATITIS
PRURITUS
PHOTOPHOBIA
NORMOCYTIC, NORMOCHROMIC ANEMIA
TREATMENT: VIT. B2
5 mg BID FOR A FEW WEEKS
3 mg/d - PROPHYLAXIS IN MALABSORPTION
SYNDROME
81. (3) Niacin=(nicotinic acid)=APF
Nicotinamide Nicotinic Acid
Niacin (nicotinic acid and nicotinamide) is also known as
vitamin B3.They are derivatives of pyridine ring. Both
nicotinic acid and nicotinamide can serve as the dietary
source of vitamin B3.
.
82. Niacin is required for the synthesis of
the active forms of vitamin B3,
Nicotinamide adenine dinucleotide
(NAD+) and nicotinamide adenine
dinucleotide phosphate (NADP+).
Both NAD+ and NADP+ function as
cofactors for numerous
dehydrogenase, e.g., lactate and
malate dehydrogenases
83. Structure of NAD+
(Hydrogen Carriers)
NADH is shown in the box insert.
The –OH phosphorylated in NADP+ is indicated by the red arrow
85. Niacin is not a true vitamin in the strictest
definition since it can be derived from the amino
acid tryptophan.
Maize is deficient in nicotinic acid, but milk &
eggs have good amounts
However, the ability to utilize tryptophan for
niacin synthesis is inefficient (60 mg of
tryptophan are required to synthesize 1 mg of
niacin).
Also, synthesis of niacin from tryptophan
requires vitamins B1, B2 and B6 which
would be limiting in themselves on a
marginal diet.
86. The recommended daily
requirement for niacin is
13 - 19 niacin equivalents
(NE) per day for a normal
adult.
One NE is equivalent to 1 mg
of free niacin.
87. Clinical Significances of
Niacin and Nicotinic Acid
A diet deficient in niacin (as well as tryptophan) leads to
glossitis of the tongue, dermatitis, weight loss, diarrhea,
depression and dementia (Pellagra = disease of 4DS).
The severe symptoms, depression, dermatitis and
diarrhea, are associated with the condition known as
Hartnup disease.
Several pathological conditions (e.g malignant carcinoid
syndrome) as well as certain drug therapies (e.g.
isoniazid= Anti-TB) can lead to niacin deficiency.
88. In Hartnup disease tryptophan
absorption is impaired and in
malignant carcinoid syndrome,
tryptophan metabolism is altered
resulting in excess serotonin
synthesis.
Isoniazid (the hydrazide derivative of
isonicotinic acid) is the primary drug
for chemotherapy of tuberculosis.
89. Nicotinic acid (but not nicotinamide) when
administered in pharmacological doses of 2 - 4 g/day
lowers plasma cholesterol levels and has been shown to
be a useful therapeutic for hypercholesterolemia.
The major action of nicotinic acid in this capacity is a
reduction in fatty acid mobilization from adipose
tissue.
Although nicotinic acid therapy lowers blood
cholesterol it also causes a depletion of glycogen stores
and fat reserves in skeletal and cardiac muscle.
Additionally, there is an elevation in blood glucose and
uric acid production.
For these reasons nicotinic acid therapy is not
recommended for diabetics or persons who suffer from
gout .
90. NIACIN (Vitamin B3)
FUNCTIONS:
COMPONENT OF NAD/NADP - ESSENTIAL FOR REDOX
REACTIONS AND HYDROGEN TRANSPORT,
METABOLISM OF CARBOHYDRATES, FATTY ACIDS,
AND PROTEINS
DIETARY SOURCES:
MEATS (LIVER), MILK, FISH, WHOLE-GRAIN, NUTS
RDI: 17-20 mg/d
92. (4) Vitamin B6
Pyridoxal, pyridoxamine and pyridoxine
are collectively known as vitamin B6.
All three compounds are efficiently converted to the
biologically active form of vitamin B6, pyridoxal phosphate (PP).
This conversion is catalyzed by the ATP requiring enzyme, pyridoxal
kinase.
Pyridoxine Pyridoxal Pyridoxamine
93. Biochemical role of Vitamin B6
1- Co- Transaminase: GPT, GOT, GGT
GPT (ALT)
Glutamic acid + Pyruvic acid a keto glutaric acid +
alanine
GOT (AST )
Glutamic acid + Oxaloacetic acid a keto glutaric acid + aspartic
acid
2- Co- Carboxylase:
in decarboxylation reactions i.e. Amine production e.g. GABA
Decarboxylase Co2
Glutamic acid Gamma amino butyric acid (GABA)
Chemical transmitter inhibit synaptic transmittion in CNS.
3- Co- Dehydratase:
94. 4- Co- Kynureninase: in tryptophane catabolism
Kynureninase
Tryptophane Kynurenine 3 hydroxy anthranilic
acid
5- Co-Trans- sulphurase:
in Trans- sulphuration reactions e.g. cystein synthesis
Serine
Methionine Homocysteine Cystathionine cysteine+Homoserine
6- Co- transfere of amino acid to cells:
amino acids incorporation inside the cells
7- Co- synthesis to Hb.
Glycine + Succinyl CoA Gamma amino Levulenic acis (G-
ALA)
95. Vitamin B6 Deficiency
1- Convulsions in very young infants due to defective GABA formation
2- Microcytic hypochromic anemia due to defective Hb
synthesis.
3- Familial Xanthurenic acid disease due to defective tryptophane
catabolism
4- Cystathioninuria due to defective cystathionase activity.
96. Vitamin B6
(PYRIDOXINE)
Forms
Pyridoxine (plant foods) active form
Pyridoxal (animal foods) Pyridoxal phosphate
Pyridoxamine (PLP)
Functions
Transamination and decarboxylation of AA
Gluconeogenesis
Formation of niacin/serotonin from tryptophan
Synthesis of lecithin, RNA, sphingolipids, heme
Immune function (IL-2, lymphocyte proliferation)
Steroid hormone modulation
98. Vitamin B6 Deficiency
Overt deficiencies are rare
Manifestations
Stomatitis, glossitis, cheilosis
Seborrheic dermatitis
Irritability, confusion, depression
Sideroblastic anemia
serum homocysteine with deficiency
risk factor for atherosclerosis / DVT
99. BIOTIN
Growth factor found in yeast, called "bios“
Called vitamin H, coenzyme R, protective factor X
Functions:
Cofactor for the carboxylases involved in CHO
and lipid metabolism
Essential in protein and DNA synthesis and cell
replication (CO2 carrier)
100. CO2 Fixation Reactions
Carboxylation reactions
e.g.
acetyl-CoA carboxylase
1- Acetyl CoA Malonyl CoA
pyruvate carboxylase
2- Pyruvate Oxaloacetate
Carbamoyl phosphate Synthetase
3- Ammonia Carbamoyl phosphate
4- Co2 Fixation Reactions IN catabolism of Odd chain FA.
101. Biotin
Dietary sources:
Liver, meats, egg yolk, soybean, yeast
Adequate dietary intake: 0.03-0.1mg/d
Biotin deficiency was first noted in patients on long-term
parenteral nutrition
Associated with consumption of large amounts of
raw egg whites which contain glycoprotein –
avidin (binds to biotin and prevents its
absorption)
103. (6) Pantothenic Acid (Anti grey hair vit.)
Pantothenic acid is also known as vitamin B5.
Pantothenic acid is formed from B-alanine and pantoic acid.
Pantothenate is required for synthesis of coenzyme A, CoA is
a component of the acyl carrier protein (ACP) domain of
fatty acid synthase (multi-enzyme complex). Pantothenate
is, therefore, required for the metabolism of carbohydrate via
the TCA cycle and all fats and proteins. At least 70 enzymes
have been identified as requiring CoA or ACP derivatives for their
function. Deficiency of pantothenic acid is extremely rare
due to its widespread distribution in whole grain cereals, legumes
and meat. Symptoms of pantothenate deficiency are difficult to assess
since they are subtle and resemble those of other B vitamin deficiencies.
104. Coenzyme A = Co-ASH
Adenine Thiol ethylamine
(Decarboxylated Systein)
Ribose Pantothenic acid
P P
105. Biochemical role of Pantothenic
Acid
1- enter in structure of Co ASH needed for activation
of FATTY ACIDS e.g.
acetic acid active acetate (acetyl Co A)
Palmitic acid Palmityl Co A
Succinic acid Succinyl Co A
2- enter in structure of ACP which is component of FAS.
ACP (Acyl Carrier Protein) carry acyl compounds.
106. Pantothenic Acid Deficiency
Deficiency occur in humans only
after intake of specific antagonists.
1- Anemia due to decrease heme synthesis.
2- Dermatitis, Hair graying and falling.
3- Suprarenal gland hemorrhage and necrosis.
107. Deficiency of Pantothenic Acid
It is rare
Manifestations
Paresthesias and dysesthesias (burning feet
syndrome)
Gastrointestinal: nausea, vomiting, cramping
Growth failure, haemorrhage and necrosis of adrenal
cortex, dermatitis, and achromotrichia (grey hair) in
rats
108. (7) Folic Acid (Folate or Folacin)
positions 7 & 8 carry hydrogens in dihydrofolate (DHF)
positions 5 - 8 carry hydrogens in tetrahydrofolate (THF)
Folic acid is a conjugated molecule consisting of a pteridine
ring structure linked to para-aminobenzoic acid (PABA)
that forms pteroic acid.
Folic acid itself is then generated through the conjugation of
glutamic acid residues to pteroic acid.
Folic acid is obtained primarily from yeasts and leafy
vegetables as well as animal liver.
Animals cannot synthesize PABA nor attach glutamate
residues to pteroic acid, thus, requiring folate intake in the
109. Folic Acid (Folate or Folacin)
Formed of Petridine ring + PABA + Glutamic acid (1 or 3 or 7)
Folate Reductase Folate Reductase
F FH2 FH4
NADPH+H+ NADP+ NADPH+H+ NADP+
FH4 IS a carrier of one carbon fragments on
(N5 to give f 5 FH4) or (N10 = f 10 FH4) or both N5,10 f 5,10
FH4
1- Formyl group (CHO)
2- Formate (HCOOH)
3- Methylene (CH2)
4- Methenyl (CH)
5- Formimino (CH=NH)
6- Methyl (CH3)
7- Hydroxy Methyl (CH2OH)
110. Folic Acid
Functions
A carrier of one-carbon groups
Synthesis of nucleic acids and protein
Dietary source
Animal products (liver)
Leafy green vegetables
Small body stores (5-10 mg)
Daily requirements: 0.2-0.4 mg/d
Pregnancy/lactation 0.5-0.8 mg/d
111. In bacteria not in humans
Folate Synthase
PABA + Petridine Folic acid FH4
this enzyme can be inhibited by sulphonamide drugs
Folate analogues & also anagonists act by
competitive inhibition to folate reductase enz. Used in
treatment of cancer & as antibacterial drug.
1- Mrthotrexate (Used in Humans & Bacteria)
2- Aminopetrine (Used in Humans & Bacteria)
3- Amethopetrine (Used in Humans & Bacteria)
4- Dimethoprim (Sulpha drug, Used only in Bacteria)
Rapidly growing cells in human bodies are
Hair cells, Leucocytes (especially neutrophils)
& cells of mucous membranes (e.g. mouth ulceration)
112. When stored in the liver or ingested, folic acid exists in a
polyglutamate form.
Intestinal mucosal cells remove some of the glutamate
residues through the action of the lysosomal enzyme,
conjugase.
The removal of glutamate residues makes folate less
negatively charged (from the polyglutamic acids) and
therefore more capable of passing through the basal
lamenal membrane of the epithelial cells of the
intestine and into the bloodstream.
Folic acid is reduced within cells (principally the liver
where it is stored) to tetrahydrofolate (THF also H4
folate) through the action of dihydrofolate reductase
(DHFR), an NADPH-requiring enzyme.
The function of THF derivatives is to carry and transfer
various forms of one carbon units during biosynthetic
reactions. The one carbon units are either methyl,
methylene, methenyl, formyl or formimino groups.
113. These one carbon transfer reactions are
required in the biosynthesis of serine, methionine,
glycine, choline and the purine nucleotides and dTMP.
The ability to acquire choline and amino acids
from the diet and to salvage the purine
nucleotides makes the role of N5,N10-
methylene-THF in dTMP synthesis the most
metabolically significant function for this vitamin.
The role of vitamin B12 and N5-methyl-THF in the
conversion of homocysteine to methionine also
can have a significant impact on the ability of cells to
regenerate needed THF.
114. Symptoms of Folate Deficiency
Macrocytic or megaloblastic anaemia
Glossitis, fatigue, diarrhoea
Progressive neurologic deterioration
Neuropathy, ataxia, seizures, mental retardation
Failure to thrive
Detection
Serum or RBC folate
Homocysteine level
Rx:
Folate 1mg/d orally x 2-3 weeks
Maintenance 0.4 mg (in MVI) with malabsorption
115. Folate Deficiency
Is commonly met with in the following conditions:
1- Anemia of infancy
2- Anemia of pregnancy
3- Anemia of Malignancy
4- Anemia of Alcoholism (alcoholism leads to
liver cirrhosis which causes Folate Deficiency)
5- Hemolytic anemia
Blood picture
shows
Macrocytic Hypochromic anemia.
Also
Leucopenia & Thrombocytopenia.
116. Clinical Significance of
Folate Deficiency
Folate deficiency results in complications
nearly identical to those described for
vitamin B12 deficiency.
The most pronounced effect of folate deficiency
on cellular processes is upon DNA
synthesis. This is due to an impairment in
dTMP synthesis which leads to cell cycle
arrest in S-phase of rapidly proliferating
cells, in particular hematopoietic cells.
The result is megaloblastic anemia as for
vitamin B12 deficiency. The inability to synthesize
DNA during erythrocyte maturation leads to abnormally
large erythrocytes termed macrocytic anemia.
117. Folate deficiencies are rare due to the adequate
presence of folate in food.
Poor dietary habits as those of chronic alcoholics can
lead to folate deficiency.
The predominant causes of folate deficiency in
non-alcoholics are impaired absorption or
metabolism or an increased demand for the vitamin.
The predominant condition requiring an increase in the
daily intake of folate is pregnancy. This is due to an
increased number of rapidly proliferating cells
present in the blood. The need for folate will
nearly double by the third trimester of pregnancy.
Certain drugs such as anticonvulsants and oral
contraceptives can impair the absorption of folate.
Anticonvulsants also increase the rate of folate
metabolism.
118. Para Amino Benzoic Acid
(8) (PABA)
Not needed in human tissues
Enter in structure of folic acid
Animal cells can not synthesis PABA.
Certain types of pathogenic bacteria can not utilize the
preformed folic acid, so these bacteria can form their
folic acid by themselves, provided that PABA is
available
PABA analogues & Antagonists
(Sulphonamides)
Folate Synthase Folate Reductase
PABA + Petridine Folic acid FH4
119. Vitamin B12 (Cobalamin )
Anti-Pernicious anemia (Extrinsic Factor)
composed of
1- Corrin Ring (Porphyrin like ring)
2- Cobalt atom (Essential for activity, Give red colure)
3- Nucleotide Side Chain
4- Cyanide group = Cyanocobalamine may be replaced by
- Hydroxyl group = Hydroxybalamine (Inside the cell )
- Methyl group = Methylbalamine (Transported Form )
- Adenosyl group = Adenosylbalamine (Stored Form )
- Nitro group = Nitrobalamine
Coenzymes of Vitamin B12
- Methyl Cobalamin
- 5`deoxy adenosyl Cobalamin
120. Vitamin B12 (Cobalamin)
Functions
A carrier for methyl group and hydrogen
Synthesis of nucleic acids, porphyrins, methionine,
and fatty acids
Dietary source
Meat
Dairy products
Daily requirement: 4-5 mcg/d
Total body stores: 2-5 mg (½ stored in the liver)
121. Factors Affecting Vitamin B12 Absorption
Dietary intake
Acid-pepsin in the stomach
Secretion of IF by gastric
parietal cells
Pancreatic proteases
Presence of ileum
124. Vitamin B12 Deficiency
Pernicious Anemia
Common in whites (northern European)
Older patients > 50years
Associated with autoimmune diseases under the
age of 30
Lack of intrinsic factor
The classic description of patient with PA
Lemon colored skin (anaemia/icterus)
Shiny tongue (atrophic glossitis)
Mentally sluggish
Shuffling broad gait
128. Treatment of Vitamin B12 Deficiency
Rx: 100-1000 mcg IM x 5-10 days, then 1000 mcg/monthly
Vegetarians: 3-6 mcg/d orally
Supplements
1) Sublingual tablet: 350 mcg/day
2) Intramuscular injection: 1000mcg/month
3) Nasal spray (Nascobal): 500mcg weekly
one nostril
4) MVI (1-15mcg)
129. One of the enzymes in this pathway, methylmalonyl-CoA
mutase, requires vitamin B12 as a cofactor in the conversion of
methylmalonyl CoA to succinyl CoA. The 5'-deoxyadenosine
derivative of cobalamin is required for this reaction.
L- methylmalonyl-CoA succinyl-
CoA
2- The second reaction requiring vitamin B12 catalyzes the
conversion of homocysteine to methionine and is catalyzed by
methionine synthase.
Methyl Transferase
Cobalamin Methyl cobalamin
N5-methyl-FH4 FH4
Methyl cobalamin
Homocystaeine Methionine
methionine synthase.
This reaction results in the transfer of the methyl group from N5-
methyltetrahydrofolate to hydroxycobalamin generating
tetrahydrofolate (THF) and methylcobalamin during the
130. Neurological complications also are associated with
vitamin B12 deficiency and result from a progressive
demyelination of nerve cells.
The demyelination is thought to result from the increase in
methylmalonyl-CoA that result from vitamin B12 deficiency.
Methylmalonyl-CoA is a competitive inhibitor of
malonyl-CoA in fatty acid biosynthesis as well as being able to
substitute for malonyl-CoA in any fatty acid biosynthesis that
may occur.
Since the myelin sheath is in continual flux the
methylmalonyl -CoA-induced inhibition of fatty acid
synthesis results in the eventual destruction of the sheath.
The incorporation methylmalonyl-CoA into fatty acid
biosynthesis results in branched-chain fatty acids being
produced that may severely alter the architecture of the
normal membrane structure of nerve cells.
Methyl Malonyl aciduria is a hereditary disease resulting
from deficiency in synthesis of methyl malonyl Co A mutase.
131. Lipoic acid, Cholin, Inositol
Not typical vitamins because
1- needed in big amounts.
2- can be formed inside the body e.g. cholin from serine.
3- enter in structure of the tissues
(10) Lipoic acid (Di-thio-octanoic acid) has a very
important roll in oxidative decarboxylation reactions (
a Ketoglutarate, Pyruvate) as hydrogen carrier.
(11) Cholin (trimethylated decarboxylated serine) enter in
formation of lecithin, sphingomyelin, plasmalogens & acetyl
cholin. Also has lipotropic action (prevent fatty liver). when
oxidized give betaine (trimethyl amino).
(12) Inositol (cyclic alcohol sugar) enter in formation of
lipositol (phosphatidyl inositol) also have lipotropic action
(prevent fatty liver).
