Vitamin B6, also known as pyridoxine, is an essential micronutrient that serves as a cofactor for many enzyme reactions in the body. The document discusses the structures and functions of various B vitamins, including their roles in metabolism and as coenzymes. It also covers fat-soluble vitamins A, D, E, K and water-soluble vitamins C and B vitamins. Common deficiency diseases are mentioned along with sources and recommended daily intake of different vitamins.
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.
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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
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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.
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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
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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.
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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.
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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.
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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.
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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
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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)
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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
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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).
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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
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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.
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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.
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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.
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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.
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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/
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43. Functions of pyridoxine
• Pyridoxal phosphate functions as a coenzyme for a large number of enzymes,
particularly those that catalyze reactions involving amino acids.
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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.
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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.
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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.
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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.
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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.
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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.
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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).
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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.
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