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JIMMA UNIVERSITY INSTITUTE OF HEALTH SCIENCE
DEPARTMENT OF PHYSIOLOGY (MSc)
BIOCHEMISTRY ASSIGNMENT
Prepared By: Temam Gemechu
Submitted To: Instructor Mengistu
5/8/2023 1
VITAMINS
5/8/2023 2
Introduction
Nutrients are divided into two classes: macronutrients and
micronutrients. Macronutrients include carbohydrates, lipids, proteins
and nucleic-acids. Vitamins and minerals are called micronutrients.
Vitamin is an organic compound that can not be synthesized by man
but is essential for normal health and development.
vitamins are heterogeneous group of compounds.
5/8/2023 3
Continued…..
They do not have any chemical or structural similarities but similar
general function in metabolism, they are studied together.
It is worth remembering the following facts when dealing with
vitamins.
1. They are needed in microgram(smaller) quantities.
2. Vitamin deficiency leads to disease
5/8/2023 4
Classifications of Vitamins
 Based on solubility Vitamins are classified;
5/8/2023 5
General features of fat soluble Vitamins
Adsorbed with dietary fat in micelles.
 Excreted much more slowly.
Stored in adipose tissue & liver so pose a greater risk of toxicity when
consumed in excess.
 Chylomicrons containing fat-soluble vitamins are transported via the
lymph to the bloodstream and eventually to the liver.
5/8/2023 6
Vitamin A
Vitamin A refers to the derivatives of beta-ionone having biological activity of
all-trans retinol.
Retinol, retinal and retinoic acid are the most commonly used vitamin A.
Three other terms used frequently with this vitamin are retinoid, carotenoids
and pro-vitamin A.
Retinoids
Comprise of
• Retinol
• Retinaldehyde
• Retinoic acid
Preformed Vitamin A found in food in animal origin
5/8/2023 7
Continued…..
Carotenoids
Comprise carotenes
Known as pro-vitamin A
 alpha,beta,gamma carotenes
 kryptoxanthin
Can be cleaved to yield
 Retinaldehyde
 Retinol
 Retinoic acid
Carotene dioxygenase
 Cleaved carotenes and other pro-vitamin A.
5/8/2023 8
The structure of Vitamin A
5/8/2023 9
Continued….
The structure of Nutritionally important Retinoids & their metabolites
5/8/2023 10
Metabolism of Vitamin A
Digestion &Transport to the liver
 Retinol esters present in the diet are hydrolyzed in the intestinal mucosa,
releasing retinol and free fatty acids.
Diets critically low in dietary fat (under about 5–10 g daily) or disease
conditions that interfere with normal digestion and absorption leading to
steatorrhea(e.g., pancreatic and liver diseases and frequent gastroenteritis)
can therefore impede the efficient absorption of retinol and carotenoids.
5/8/2023 11
Continued…
Retinol derived from esters and from the cleavage and reduction of
carotenes is re-esterified to long-chain fatty acids in the intestinal
mucosa and secreted as a component of chylomicrons into the
lymphatic system and delivered to the blood through the thoracic duct.
Retinol esters contained in chylomicron remnants are taken up by, and
stored in, the liver.
5/8/2023 12
Continued….
5/8/2023 13
Functions of Vitamin A
1. Involved in visual cycle: Rhodopsin, the visual pigment of the rods
in the retina, consists of 11 cis-retinal specifically bound to the
protein opsin.
when a person shifts from a bright light to dim light, rhodopsin stores
are depleted and vision is impaired.
However, within few minutes, known as dark adaptation time,
rhodopsin is resynthesized and vision is improved.
 Dark adaptation time is increased in Vitamin A deficient individuals.
5/8/2023 14
Continued….
2.For growth and development.
 All-trans retinoic acid and 9-cis-retinoic acid regulate growth,
development, and tissue differentiation ( acts like hormone).
3. For reproduction: Retinol and retinal support spermatogenesis in the
male and prevents fetal resorption in the female.
4. Maintenance of epithelial cell: Essential for normal differentiation of
epithelial tissues and mucus secretion.
6. Maintains the antioxidant potential of different tissues(Anticancer
effect).
7. The Immune Response
8. For synthesis of transferrin
9. Been used dermatologically in treatment of acne, psoriasis
5/8/2023 15
Sources of Vitamin A
Vitamin A comes from animal sources such as meat, egg , fish & diary products.
Beta- carotene, a precursor of Vitamin A comes from green, leafy vegetables &
intensely colored fruits & vegetables.
Daily requirement: 2-3 mg
Hypervitaminosis A/Toxicity of retinoids
Results from excessive intake of
Vitamin A (intake of > 7.5 mg/day)
5/8/2023 16
Vitamins D
The two most prominent members of this group are vitamin D2 (ergocalciferol)
and vitamin D3 (cholecalciferol).
Vitamin D2(C28H44O) is derived from a common plant steroid, ergo sterol.
Vitamin D3(C27H44O) is the form of vitamin D obtained when radiant energy
from the sun strikes the skin and converts the precursor 7-dehydrocholesterol.
5/8/2023 17
Continued…
Since the body is capable of producing vitamin D3, vitamin D does
not meet the classical definition of a vitamin.
A more accurate description of vitamin D is that it is a prohormone;
thus, vitamin D is metabolized to a biologically active form that
functions as a steroid hormone.
5/8/2023 18
The structure and activation of vitamin D
• It may be noted that the two vitamins, D2 and D3 differ only in their side chains
attached to C17.
5/8/2023 19
Metabolism of Vitamin D/ activation
The production of 25(OH)D3 is catalyzed by the cytochrome P450 enzyme,
vitamin D3 25-hydroxylase. The 25-hydroxylase activity is found in both liver
microsomes and mitochondria.
From the liver, 25(OH)D3 is returned to the circulatory system where it is
transported via DBP to the kidney where a second hydroxyl group can be added
at the C-1 position by the 25(OH)D3-1-α-hydroxylase.
5/8/2023 20
Continued..
1,25(OH)2D3 is transported by the blood to intestinal mucosa and bone (target
tissues), where it functions in the processes for the absorption, reabsorption and
mobilization of calcium and phosphate ions.
In conjunction with parathyroid hormone and calcitonin, it has a major role in
homeostasis of Ca and P in the body’s fluids and tissues.
Thus, the function of vitamin D is to cause increased absorption, longer
retention and better utilization of calcium and phosphorus in the body.
5/8/2023 21
Continued…
Recently, 1α,25(OH)2D3 has been shown to act on novel target tissues
not related to calcium homeostasis.
These studies suggest that vitamin D status is important for insulin
and prolactin secretion, muscle function, immune and stress response,
melanin synthesis, and cellular differentiation of skin and blood cells.
5/8/2023 22
Vitamin D Deficiency Syndromes
Rickets- There is under mineralization of bone in children due to less
absorption of Calcium.
Osteomalacia – clinical manifestation of Vitamin D deficiency in adults.
Results due to demineralization of bone.
Vitamin D Toxicity/Hypervitaminosis D
Serum concentrations of both calcium and phosphate are greatly raised,
resulting in metabolic calcification of many soft tissues and the formation
of renal calculi.
5/8/2023 23
Vitamin E
• Consists of eight naturally occurring tocopherols, of which α-tocopherol is the
most active.
• It does act as a lipid-soluble antioxidant in cell membranes, where many of its
functions can be provided by synthetic antioxidants.
• Vitamin E is the generic descriptor for two families of compounds, the
tocopherols and the tocotrienols.
5/8/2023 24
Continued..
the biological activity of vitamin E is mainly attributed to their ability
to donate their phenolic hydrogen to lipid free radicals.
Tocopherols, as well as tocotrienols, can react with peroxyl radicals
more rapidly than can polyunsaturated fatty acids and, therefore, are
very effective free-radical chain-breaking antioxidants.
5/8/2023 25
Continued…
Antioxidant activity of tocopherols is determined by their chemical
reactivity with molecular oxygen, superoxide radicals, peroxyl
radicals, or other radicals, or by their ability to inhibit autoxidation of
fats and oils.
It is for this reason that they are commercially added to foods to retard
their spoilage.
5/8/2023 26
Continued…
The tocopheroxyl radical is reduced back to tocopherol by reaction
with Vit C from plasma.
The resultant monodehydroascorbate free radical then undergoes
enzymic or nonenzymic reaction to yield ascorbate &
dehydroascorbate, neither of which is a free radical.
5/8/2023 27
Vitamin K
Exists in several forms:
a. Phylloquinone (Vit.k1) – present in plants.
b. Menaquinone (Vit. K2) – present in intestinal bacterial flora.
c. Menadione, menadiol and menadiol acetate
– a synthetic derivative
Functions:
a. Formation of mature clotting factors.
b. Promotes blood clotting on surface of platelets.
5/8/2023 28
Structure of vitamin K
5/8/2023 29
Role of vitamin K in blood coagulation
Vitamin K is a Coenzyme for carboxylation of Glutamate, so Vitamin
K promotes the carboxylation of the glutamic acid residues of the
precursors of clotting factors II, VII, IX and X.
Carboxylation produces mature forms of the clotting factors and hence
capable of subsequent activation.
Vitamin K is also important in the synthesis of bone calcium-binding
proteins.
5/8/2023 30
General features of water soluble Vitamins
 Readily excreted by kidney.
Function as a coenzyme & in energy metabolism .
Vitamin C, thiamin and riboflavin are especially susceptible to heat
and alkalinity.
Hydrophilic compounds and water leach them from vegetables .
 Marginal deficiency more common.
5/8/2023 31
Ascorbic acid (vitamin C)
The active form of vitamin C is ascorbic acid.
Vitamin C is designated as ascorbic acid because of its ability to cure and
prevent scurvy.
5/8/2023 32
Functions of vitamin C
The main function of ascorbate is as a reducing agent in several different
reactions & O2 radical quencher (antioxidant).
Vitamin C has a well-documented role as a coenzyme in hydroxylation
reactions, for example, hydroxylation of prolyl and lysyl residues of collagen.
Vitamin C also facilitates the absorption of dietary iron from the intestine.
A deficiency of ascorbic acid results in scurvy, a disease characterized by
sore and spongy gums, loose teeth, fragile blood vessels, swollen joints, and
anemia
5/8/2023 33
Thiamine (Vitamin B1)
Thiamine pyrophosphate (TPP), the active form of the vitamin, is
formed by the transfer of a pyrophosphate group from ATP to
thiamine.
Thiamine diphosphate is the coenzyme in the 3 multi enzyme complex
that catalyze oxidative decarboxylation
• PDH-complex– carbohydrate metabolism
• KGDH-complex– TCA cycle
• Branched chain keto acid dehaydrogenase – branch chain AAs
It is also a coenzyme for transketolase in PPP (pentose phosphate
pathway).
5/8/2023 34
The structure of thiamine & its active form TPP
5/8/2023 35
Thiamine Deficiencies
1. Beriberi is a severe thiamine deficiency syndrome.
• Infantile form manifests as tachycardia, vomiting, convulsions and
death if untreated.
• Adult forms – dry skin, irritability, wasting, disorderly thinking and
progressive paralysis.
2. Wernicke-Korsakoffs syndrome – thiamine deficiency in association
with chronic alcoholism. It is due to dietary insufficiency or impaired
intestinal absorption of the vitamin.
3. Lactic acidosis
5/8/2023 36
Riboflavin (Vitamin B2)
• There are 2 biologically active forms of riboflavin: Flavin
Mononucleotide(FMN) and Flavin Adenine Dinucleotide (FAD).
• FMN is formed by the transfer of phosphate ion from ATP to riboflavin.
• FAD is formed by the transfer of AMP from ATP to FMN.
5/8/2023 37
Role of FMN and FAD in redox reactions
Both FMN and FAD are components of NADH dehydrogenase and
succinate dehydrogenase/glycerol 3-P dehydrogenase respectively, that
are capable of accepting electrons and donating electrons to the other
components of the ETC system.
 With severe deficiency of riboflavin, there is decreased ATP synthesis
by the mitochondria via oxidative phosphorylation.
FAD and FMN also plays role In Nitric Oxide (NO) synthesis.
5/8/2023 38
NIACIN (NICOTINIC ACID, VITAMIN B3)
• The term niacin is used to describe chemicals having biological activity
associated with nicotinamide, including nicotinamide, nicotinic acid, and a
variety of pyridine nucleotide structures.
5/8/2023 39
Functions of niacin
1. The biologically active forms of niacin are Nicotinamide Adenine
Dinucleotide (NAD+) and its phosphorylated derivative, Nicotinamide
Adenine Dinucleotide Phosphate (NADP)+).
3. NAD+ and NADP+ serve as coenzymes in many oxidation-reductions
reactions.
4. Also a source of ADP-ribose in nuclear proteins. Poly(ADP-ribose)
synthesis makes use of NADP as substrate, rather than as an electron-
transporting intermediate. Poly(ADP-ribose) formation has been
shown to be important in DNA repair and genomic stability and
provides an explanation for sensitivity to ultraviolet radiation
observed in pellagra.
5/8/2023 40
Pyridoxine (vitamin B6)
Vitamin B6 is a collective term for pyridoxine, pyridoxal, and pyridoxamine, all
derivatives of pyridine.
Pyridoxine occurs primarily in plants, whereas pyridoxal and pyridoxamine are
found in foods obtained from animals.
They differ only in the nature of the functional group attached to the ring.
These three compounds can serve as precursors of the biologically active
coenzyme, pyridoxal phosphate /PLP/
5/8/2023 41
Structures of vitamin B6
5/8/2023 42
Functions of pyridoxine
• Pyridoxal phosphate functions as a coenzyme for a large number of enzymes,
particularly those that catalyze reactions involving amino acids.
5/8/2023 43
Continued….
Isoniazid (isonicotinic acid hydrazide), a drug frequently used to treat
tuberculosis, can induce a vitamin B6 deficiency by forming an inactive
derivative with pyridoxal phosphate.
Dietary supplementation with B6 is, thus, an adjunct to isoniazid
treatment.
Toxicity of pyridoxine
Pyridoxine is the only water-soluble vitamin with significant toxicity.
5/8/2023 44
BIOTIN/anti-egg white injury factor
Biotin is a coenzyme in carboxylation reactions, in which it serves as
a carrier of activated carbon dioxide.
Biotin is covalently bound to the ε-amino groups of lysine residues in
biotin-dependent enzymes.
Also, a large percentage of the biotin requirement in humans is
supplied by intestinal bacteria.
Raw egg white contains a glycoprotein, avidin, which tightly binds
biotin and prevents its absorption from the intestine.
Native avidin is resistant to intestinal proteolysis in both the free and
biotin combined form.
5/8/2023 45
Continued…
5/8/2023 46
Pantothenic acid
Pantothenic acid is a component of Coenzyme A, which therefore
functions in the transfer of acyl groups because of its thiol (SH) group.
Coenzyme A takes part in reactions of the TCA cycle, FA synthesis and
oxidation, acylations and cholesterol synthesis.
5/8/2023 47
Folic acid (Pteroyl glutamate)
Folic acid (or folate), which plays a key role in one-carbon metabolism, is
essential for the biosynthesis of several compounds.
Tetra hydro folate (reduced folate) receives one-carbon fragments from
donors such as serine, glycine, and histidine and transfers them to
intermediates in the synthesis of amino acids, purines, and thymidine
mono phosphate (TMP)—a pyrimidine found in DNA.
The active form of folic acid is tetrahydrofolate (THF).
Different forms of THF are used in the synthesis of amino acids, purines,
and thymine – a pyrimidine found in DNA.
5/8/2023 48
Folate and anemia
Inadequate serum levels of folate can be caused by increased demand (for
example, pregnancy and lactation), poor absorption caused by pathology of the
small intestine, alcoholism, or treatment with drugs that are dihydrofolate
reductase inhibitors, for example, methotrexate.
A primary result of folic acid deficiency is megaloblastic anemia , caused by
diminished synthesis of purines and TMP, which leads to an inability of cells
(including red cell precursors) to make DNA and, therefore, they cannot divide.
5/8/2023 49
COBALAMIN (VITAMIN B12)
• Vitamin B12 is required in humans for two essential enzymatic reactions: the
remethylation of homocysteine to methionine and the isomerization of
methylmalonyl coenzyme A (CoA) that is produced during the degradation of
some amino acids, and fatty acids with odd numbers of carbon.
• With deficiency of Vitamin B12, there is impaired methionine synthase activity,
resulting in the accumulation of N5-Methyltetrahydrofolate with a decrease of
the other forms of tetrahydrofolate.
5/8/2023 50
Continued….
5/8/2023 51
Continued…
Cobalamin contains a corrin ring system that differs from the porphyrins in
that 2 of the pyrrole rings are linked directly rather than via a methene
bridge.
Cobalt is held in the center of the corrin ring.
5,6-dimethylbenzimidazole and cyanide fill up 2 of the 4 coordination sites
of the corrin ring.
The coenzyme forms of cobalamin are 5’-deoxyadenosylcobalamin
(cyanide is replaced with 5’-deoxy adenosine and methylcobalamin
(cyanide is replaced by a methyl group).
5/8/2023 52
Continued..
5/8/2023 53
Pernicious anemia due to vitamin B12 deficiency
Vitamin B12 absorption requires an intrinsic factor (IF) produced by the
gastric parietal cells.
This cobalamin-intrinsic factor complex travels through the gut and into
the general circulation.
In the presence of an autoimmune destruction of the gastric parietal cells,
the deficiency of intrinsic factor prevents absorption of Vitamin. B12,
resulting to a clinical condition called pernicious anemia.
5/8/2023 54
Thank you
5/8/2023 55

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vitamins.pptx

  • 1. JIMMA UNIVERSITY INSTITUTE OF HEALTH SCIENCE DEPARTMENT OF PHYSIOLOGY (MSc) BIOCHEMISTRY ASSIGNMENT Prepared By: Temam Gemechu Submitted To: Instructor Mengistu 5/8/2023 1
  • 3. Introduction Nutrients are divided into two classes: macronutrients and micronutrients. Macronutrients include carbohydrates, lipids, proteins and nucleic-acids. Vitamins and minerals are called micronutrients. Vitamin is an organic compound that can not be synthesized by man but is essential for normal health and development. vitamins are heterogeneous group of compounds. 5/8/2023 3
  • 4. Continued….. They do not have any chemical or structural similarities but similar general function in metabolism, they are studied together. It is worth remembering the following facts when dealing with vitamins. 1. They are needed in microgram(smaller) quantities. 2. Vitamin deficiency leads to disease 5/8/2023 4
  • 5. Classifications of Vitamins  Based on solubility Vitamins are classified; 5/8/2023 5
  • 6. General features of fat soluble Vitamins Adsorbed with dietary fat in micelles.  Excreted much more slowly. Stored in adipose tissue & liver so pose a greater risk of toxicity when consumed in excess.  Chylomicrons containing fat-soluble vitamins are transported via the lymph to the bloodstream and eventually to the liver. 5/8/2023 6
  • 7. Vitamin A Vitamin A refers to the derivatives of beta-ionone having biological activity of all-trans retinol. Retinol, retinal and retinoic acid are the most commonly used vitamin A. Three other terms used frequently with this vitamin are retinoid, carotenoids and pro-vitamin A. Retinoids Comprise of • Retinol • Retinaldehyde • Retinoic acid Preformed Vitamin A found in food in animal origin 5/8/2023 7
  • 8. Continued….. Carotenoids Comprise carotenes Known as pro-vitamin A  alpha,beta,gamma carotenes  kryptoxanthin Can be cleaved to yield  Retinaldehyde  Retinol  Retinoic acid Carotene dioxygenase  Cleaved carotenes and other pro-vitamin A. 5/8/2023 8
  • 9. The structure of Vitamin A 5/8/2023 9
  • 10. Continued…. The structure of Nutritionally important Retinoids & their metabolites 5/8/2023 10
  • 11. Metabolism of Vitamin A Digestion &Transport to the liver  Retinol esters present in the diet are hydrolyzed in the intestinal mucosa, releasing retinol and free fatty acids. Diets critically low in dietary fat (under about 5–10 g daily) or disease conditions that interfere with normal digestion and absorption leading to steatorrhea(e.g., pancreatic and liver diseases and frequent gastroenteritis) can therefore impede the efficient absorption of retinol and carotenoids. 5/8/2023 11
  • 12. Continued… Retinol derived from esters and from the cleavage and reduction of carotenes is re-esterified to long-chain fatty acids in the intestinal mucosa and secreted as a component of chylomicrons into the lymphatic system and delivered to the blood through the thoracic duct. Retinol esters contained in chylomicron remnants are taken up by, and stored in, the liver. 5/8/2023 12
  • 14. Functions of Vitamin A 1. Involved in visual cycle: Rhodopsin, the visual pigment of the rods in the retina, consists of 11 cis-retinal specifically bound to the protein opsin. when a person shifts from a bright light to dim light, rhodopsin stores are depleted and vision is impaired. However, within few minutes, known as dark adaptation time, rhodopsin is resynthesized and vision is improved.  Dark adaptation time is increased in Vitamin A deficient individuals. 5/8/2023 14
  • 15. Continued…. 2.For growth and development.  All-trans retinoic acid and 9-cis-retinoic acid regulate growth, development, and tissue differentiation ( acts like hormone). 3. For reproduction: Retinol and retinal support spermatogenesis in the male and prevents fetal resorption in the female. 4. Maintenance of epithelial cell: Essential for normal differentiation of epithelial tissues and mucus secretion. 6. Maintains the antioxidant potential of different tissues(Anticancer effect). 7. The Immune Response 8. For synthesis of transferrin 9. Been used dermatologically in treatment of acne, psoriasis 5/8/2023 15
  • 16. Sources of Vitamin A Vitamin A comes from animal sources such as meat, egg , fish & diary products. Beta- carotene, a precursor of Vitamin A comes from green, leafy vegetables & intensely colored fruits & vegetables. Daily requirement: 2-3 mg Hypervitaminosis A/Toxicity of retinoids Results from excessive intake of Vitamin A (intake of > 7.5 mg/day) 5/8/2023 16
  • 17. Vitamins D The two most prominent members of this group are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Vitamin D2(C28H44O) is derived from a common plant steroid, ergo sterol. Vitamin D3(C27H44O) is the form of vitamin D obtained when radiant energy from the sun strikes the skin and converts the precursor 7-dehydrocholesterol. 5/8/2023 17
  • 18. Continued… Since the body is capable of producing vitamin D3, vitamin D does not meet the classical definition of a vitamin. A more accurate description of vitamin D is that it is a prohormone; thus, vitamin D is metabolized to a biologically active form that functions as a steroid hormone. 5/8/2023 18
  • 19. The structure and activation of vitamin D • It may be noted that the two vitamins, D2 and D3 differ only in their side chains attached to C17. 5/8/2023 19
  • 20. Metabolism of Vitamin D/ activation The production of 25(OH)D3 is catalyzed by the cytochrome P450 enzyme, vitamin D3 25-hydroxylase. The 25-hydroxylase activity is found in both liver microsomes and mitochondria. From the liver, 25(OH)D3 is returned to the circulatory system where it is transported via DBP to the kidney where a second hydroxyl group can be added at the C-1 position by the 25(OH)D3-1-α-hydroxylase. 5/8/2023 20
  • 21. Continued.. 1,25(OH)2D3 is transported by the blood to intestinal mucosa and bone (target tissues), where it functions in the processes for the absorption, reabsorption and mobilization of calcium and phosphate ions. In conjunction with parathyroid hormone and calcitonin, it has a major role in homeostasis of Ca and P in the body’s fluids and tissues. Thus, the function of vitamin D is to cause increased absorption, longer retention and better utilization of calcium and phosphorus in the body. 5/8/2023 21
  • 22. Continued… Recently, 1α,25(OH)2D3 has been shown to act on novel target tissues not related to calcium homeostasis. These studies suggest that vitamin D status is important for insulin and prolactin secretion, muscle function, immune and stress response, melanin synthesis, and cellular differentiation of skin and blood cells. 5/8/2023 22
  • 23. Vitamin D Deficiency Syndromes Rickets- There is under mineralization of bone in children due to less absorption of Calcium. Osteomalacia – clinical manifestation of Vitamin D deficiency in adults. Results due to demineralization of bone. Vitamin D Toxicity/Hypervitaminosis D Serum concentrations of both calcium and phosphate are greatly raised, resulting in metabolic calcification of many soft tissues and the formation of renal calculi. 5/8/2023 23
  • 24. Vitamin E • Consists of eight naturally occurring tocopherols, of which α-tocopherol is the most active. • It does act as a lipid-soluble antioxidant in cell membranes, where many of its functions can be provided by synthetic antioxidants. • Vitamin E is the generic descriptor for two families of compounds, the tocopherols and the tocotrienols. 5/8/2023 24
  • 25. Continued.. the biological activity of vitamin E is mainly attributed to their ability to donate their phenolic hydrogen to lipid free radicals. Tocopherols, as well as tocotrienols, can react with peroxyl radicals more rapidly than can polyunsaturated fatty acids and, therefore, are very effective free-radical chain-breaking antioxidants. 5/8/2023 25
  • 26. Continued… Antioxidant activity of tocopherols is determined by their chemical reactivity with molecular oxygen, superoxide radicals, peroxyl radicals, or other radicals, or by their ability to inhibit autoxidation of fats and oils. It is for this reason that they are commercially added to foods to retard their spoilage. 5/8/2023 26
  • 27. Continued… The tocopheroxyl radical is reduced back to tocopherol by reaction with Vit C from plasma. The resultant monodehydroascorbate free radical then undergoes enzymic or nonenzymic reaction to yield ascorbate & dehydroascorbate, neither of which is a free radical. 5/8/2023 27
  • 28. Vitamin K Exists in several forms: a. Phylloquinone (Vit.k1) – present in plants. b. Menaquinone (Vit. K2) – present in intestinal bacterial flora. c. Menadione, menadiol and menadiol acetate – a synthetic derivative Functions: a. Formation of mature clotting factors. b. Promotes blood clotting on surface of platelets. 5/8/2023 28
  • 29. Structure of vitamin K 5/8/2023 29
  • 30. Role of vitamin K in blood coagulation Vitamin K is a Coenzyme for carboxylation of Glutamate, so Vitamin K promotes the carboxylation of the glutamic acid residues of the precursors of clotting factors II, VII, IX and X. Carboxylation produces mature forms of the clotting factors and hence capable of subsequent activation. Vitamin K is also important in the synthesis of bone calcium-binding proteins. 5/8/2023 30
  • 31. General features of water soluble Vitamins  Readily excreted by kidney. Function as a coenzyme & in energy metabolism . Vitamin C, thiamin and riboflavin are especially susceptible to heat and alkalinity. Hydrophilic compounds and water leach them from vegetables .  Marginal deficiency more common. 5/8/2023 31
  • 32. Ascorbic acid (vitamin C) The active form of vitamin C is ascorbic acid. Vitamin C is designated as ascorbic acid because of its ability to cure and prevent scurvy. 5/8/2023 32
  • 33. Functions of vitamin C The main function of ascorbate is as a reducing agent in several different reactions & O2 radical quencher (antioxidant). Vitamin C has a well-documented role as a coenzyme in hydroxylation reactions, for example, hydroxylation of prolyl and lysyl residues of collagen. Vitamin C also facilitates the absorption of dietary iron from the intestine. A deficiency of ascorbic acid results in scurvy, a disease characterized by sore and spongy gums, loose teeth, fragile blood vessels, swollen joints, and anemia 5/8/2023 33
  • 34. Thiamine (Vitamin B1) Thiamine pyrophosphate (TPP), the active form of the vitamin, is formed by the transfer of a pyrophosphate group from ATP to thiamine. Thiamine diphosphate is the coenzyme in the 3 multi enzyme complex that catalyze oxidative decarboxylation • PDH-complex– carbohydrate metabolism • KGDH-complex– TCA cycle • Branched chain keto acid dehaydrogenase – branch chain AAs It is also a coenzyme for transketolase in PPP (pentose phosphate pathway). 5/8/2023 34
  • 35. The structure of thiamine & its active form TPP 5/8/2023 35
  • 36. Thiamine Deficiencies 1. Beriberi is a severe thiamine deficiency syndrome. • Infantile form manifests as tachycardia, vomiting, convulsions and death if untreated. • Adult forms – dry skin, irritability, wasting, disorderly thinking and progressive paralysis. 2. Wernicke-Korsakoffs syndrome – thiamine deficiency in association with chronic alcoholism. It is due to dietary insufficiency or impaired intestinal absorption of the vitamin. 3. Lactic acidosis 5/8/2023 36
  • 37. Riboflavin (Vitamin B2) • There are 2 biologically active forms of riboflavin: Flavin Mononucleotide(FMN) and Flavin Adenine Dinucleotide (FAD). • FMN is formed by the transfer of phosphate ion from ATP to riboflavin. • FAD is formed by the transfer of AMP from ATP to FMN. 5/8/2023 37
  • 38. Role of FMN and FAD in redox reactions Both FMN and FAD are components of NADH dehydrogenase and succinate dehydrogenase/glycerol 3-P dehydrogenase respectively, that are capable of accepting electrons and donating electrons to the other components of the ETC system.  With severe deficiency of riboflavin, there is decreased ATP synthesis by the mitochondria via oxidative phosphorylation. FAD and FMN also plays role In Nitric Oxide (NO) synthesis. 5/8/2023 38
  • 39. NIACIN (NICOTINIC ACID, VITAMIN B3) • The term niacin is used to describe chemicals having biological activity associated with nicotinamide, including nicotinamide, nicotinic acid, and a variety of pyridine nucleotide structures. 5/8/2023 39
  • 40. Functions of niacin 1. The biologically active forms of niacin are Nicotinamide Adenine Dinucleotide (NAD+) and its phosphorylated derivative, Nicotinamide Adenine Dinucleotide Phosphate (NADP)+). 3. NAD+ and NADP+ serve as coenzymes in many oxidation-reductions reactions. 4. Also a source of ADP-ribose in nuclear proteins. Poly(ADP-ribose) synthesis makes use of NADP as substrate, rather than as an electron- transporting intermediate. Poly(ADP-ribose) formation has been shown to be important in DNA repair and genomic stability and provides an explanation for sensitivity to ultraviolet radiation observed in pellagra. 5/8/2023 40
  • 41. Pyridoxine (vitamin B6) Vitamin B6 is a collective term for pyridoxine, pyridoxal, and pyridoxamine, all derivatives of pyridine. Pyridoxine occurs primarily in plants, whereas pyridoxal and pyridoxamine are found in foods obtained from animals. They differ only in the nature of the functional group attached to the ring. These three compounds can serve as precursors of the biologically active coenzyme, pyridoxal phosphate /PLP/ 5/8/2023 41
  • 42. Structures of vitamin B6 5/8/2023 42
  • 43. Functions of pyridoxine • Pyridoxal phosphate functions as a coenzyme for a large number of enzymes, particularly those that catalyze reactions involving amino acids. 5/8/2023 43
  • 44. Continued…. Isoniazid (isonicotinic acid hydrazide), a drug frequently used to treat tuberculosis, can induce a vitamin B6 deficiency by forming an inactive derivative with pyridoxal phosphate. Dietary supplementation with B6 is, thus, an adjunct to isoniazid treatment. Toxicity of pyridoxine Pyridoxine is the only water-soluble vitamin with significant toxicity. 5/8/2023 44
  • 45. BIOTIN/anti-egg white injury factor Biotin is a coenzyme in carboxylation reactions, in which it serves as a carrier of activated carbon dioxide. Biotin is covalently bound to the ε-amino groups of lysine residues in biotin-dependent enzymes. Also, a large percentage of the biotin requirement in humans is supplied by intestinal bacteria. Raw egg white contains a glycoprotein, avidin, which tightly binds biotin and prevents its absorption from the intestine. Native avidin is resistant to intestinal proteolysis in both the free and biotin combined form. 5/8/2023 45
  • 47. Pantothenic acid Pantothenic acid is a component of Coenzyme A, which therefore functions in the transfer of acyl groups because of its thiol (SH) group. Coenzyme A takes part in reactions of the TCA cycle, FA synthesis and oxidation, acylations and cholesterol synthesis. 5/8/2023 47
  • 48. Folic acid (Pteroyl glutamate) Folic acid (or folate), which plays a key role in one-carbon metabolism, is essential for the biosynthesis of several compounds. Tetra hydro folate (reduced folate) receives one-carbon fragments from donors such as serine, glycine, and histidine and transfers them to intermediates in the synthesis of amino acids, purines, and thymidine mono phosphate (TMP)—a pyrimidine found in DNA. The active form of folic acid is tetrahydrofolate (THF). Different forms of THF are used in the synthesis of amino acids, purines, and thymine – a pyrimidine found in DNA. 5/8/2023 48
  • 49. Folate and anemia Inadequate serum levels of folate can be caused by increased demand (for example, pregnancy and lactation), poor absorption caused by pathology of the small intestine, alcoholism, or treatment with drugs that are dihydrofolate reductase inhibitors, for example, methotrexate. A primary result of folic acid deficiency is megaloblastic anemia , caused by diminished synthesis of purines and TMP, which leads to an inability of cells (including red cell precursors) to make DNA and, therefore, they cannot divide. 5/8/2023 49
  • 50. COBALAMIN (VITAMIN B12) • Vitamin B12 is required in humans for two essential enzymatic reactions: the remethylation of homocysteine to methionine and the isomerization of methylmalonyl coenzyme A (CoA) that is produced during the degradation of some amino acids, and fatty acids with odd numbers of carbon. • With deficiency of Vitamin B12, there is impaired methionine synthase activity, resulting in the accumulation of N5-Methyltetrahydrofolate with a decrease of the other forms of tetrahydrofolate. 5/8/2023 50
  • 52. Continued… Cobalamin contains a corrin ring system that differs from the porphyrins in that 2 of the pyrrole rings are linked directly rather than via a methene bridge. Cobalt is held in the center of the corrin ring. 5,6-dimethylbenzimidazole and cyanide fill up 2 of the 4 coordination sites of the corrin ring. The coenzyme forms of cobalamin are 5’-deoxyadenosylcobalamin (cyanide is replaced with 5’-deoxy adenosine and methylcobalamin (cyanide is replaced by a methyl group). 5/8/2023 52
  • 54. Pernicious anemia due to vitamin B12 deficiency Vitamin B12 absorption requires an intrinsic factor (IF) produced by the gastric parietal cells. This cobalamin-intrinsic factor complex travels through the gut and into the general circulation. In the presence of an autoimmune destruction of the gastric parietal cells, the deficiency of intrinsic factor prevents absorption of Vitamin. B12, resulting to a clinical condition called pernicious anemia. 5/8/2023 54