1. Principle of Biochemistry
7-Vitamins and Cofactors
Course code: HFB324
Credit hours: 3 hours
Dr. Siham Gritly
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2. Lecture content
• Vitamins: Definition, classification,
requirements and chemical properties.
Importance of vitamins to biological processes
of the living body.
• vitamins deficiencies.
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3. • Vitamin (water soluble vitamin, fat soluble
vitamin): an organic substance needed in small
amounts for normal body functions that the body
cannot synthesize in adequate amounts
• enzyme: a protein that is a catalyst
• cofactor: a small, inorganic or organic substance
that facilitates enzyme action; includes bothorganic
coenzymes made from vitamins and inorganic
substances such as minerals
• Coenzymes are non-protein organic molecules that
are mostly derivatives of vitamins soluble in water by
phosphorylation; they bind apoenzyme to proteins to
produce an active holoenzyme
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4. • prosthetic group: a cofactor permanently
associated with the protein, often covalently bound
• holoenzyme: catalytically active enzyme-cofactor
complex.
• apoenzyme: an enzyme without its cofactor
enzymatically inactive protein
• FADH2 flavin adenine dinucleotide (reduced form); a
molecule, central to metabolism, which carries a pair
of electrons only slightly less energetic than those of
NADH
• NADH nicotinamide adenine dinucleotide (reduced
form); a molecule, central to metabolism, which
carries a pair of high-energy electrons
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5. • free radicals: unstable and highly reactive atoms or
molecules that have one or more unpaired electrons in
the outer orbital
• 1,25-dihydroxyvitamin D: vitamin D that is made from
the hydroxylation of calcidiol in the kidneys; the
biologically active hormone; also called calcitriol or
active vitamin D.
• 25-hydroxyvitamin D: vitamin D found in the
• blood that is made from the hydroxylation of
cholecalciferol in the liver; also called calcidiol
• acetyl CoA; a 2-carbon compound (acetate, or acetic
acid) to which a molecule of CoA is attached.
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6. • antioxidant: a substance that signifi cantly
decreases the adverse effects of free radicals
on normal physiological functions
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7. Vitamins
• Vitamins are organic molecules needed for variety of
biological function within the body.
• The most important function of the vitamins is to serve
as cofactors (co-enzymes) for enzymatic reactions.
• protein + coenzyme (vitamin)= enzyme
• protein + cofactor (metal ion)= enzyme
• the vitamins cannot be synthesized by mammalian cells
and, therefore, must be supplied in the diet in small
quantities (microgram or milligram per day).
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8. Coenzyme and vitamins
• Most of the B vitamins are coenzymes and are essential in
facilitating the transfer of atoms or groups of atoms between
molecules in the formation of carbohydrates, fats, and proteins
• coenzymes: complex organic molecules that work with
enzymes to facilitate the enzymes’ activity. Many coenzymes
have B vitamins as part of their structures.
• coenzymes is to act as transporters of chemical groups from
one reactant to another.
• Examples include;
• - nicotinamide adenine dinucleotide (NAD), which accepts
hydrogen (and gives it up in another reaction),
• -ATP, which gives up phosphate groups while transferring
chemical energy
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9. The vitamins are of two distinct types, water
soluble and fat soluble.
Water Soluble Vitamins Fat Soluble Vitamins
Thiamin (B1) Vitamin A
Riboflavin (B2)
Niacin (B3) Vitamin D
Pantothenic Acid (B5)
Pyridoxal, Pyridoxamine, Vitamin E
Pyridoxine (B6)
Biotin Vitamin K
Cobalamin (B12)
Folic Acid
Ascorbic Acid
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10. Water soluble vitamins
• -soluble in water, consist of carbon, hydrogen,
oxygen nitrogen, sulfur, cobalt,
• -deficiency usually occur more than fat soluble
vitamins
• -Water-soluble vitamins that body cannot store
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11. • -enter in energy production and in essential
enzyme system. They help with release of energy
from carbohydrates, proteins, and fats
• -activate chemical reaction inside the body and
act as coenzymes
• -excretion in urine through urination
• -the most important water soluble vitamins are B
complex and vitamin C
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12. Thiamine or vitamin B1
• thiamine-sulfur containing water soluble
vitamin of B complex, exist in tissues in the
active form of Thiamine Pyrophosphate
(TPP)
• - Thiamine Pyrophosphate (TPP) is essential
co-enzyme involve in energy extraction and
cellular process in catabolism of sugar and
amino acid
• -human and other animal obtain it through diet
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13. • The majority of thiamine in serum is bound to
proteins, mainly albumin.
• Approximately 90% of total thiamine in blood
is in erythrocytes (red blood cell).
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14. Thiamin chemical structure
Thiamin is derived from a substituted
aminopyrimidine ring and a thiazole ring with
methyl and hydroxyethyl side chains linked by a
methylene bridge. C12 H17N4OS
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15. Thiamin pyrophosphate the active form of vitamin
B1 A thiazole ring is found naturally in thiamin
Thiazole is a heterocyclic compound featuring both a
nitrogen atom and sulfur atom as part of the aromatic
five-membered ring. a thiazole ring stabilizes charge
and electron transfer
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16. • Thiamin is rapidly converted to its active form,
thiamin pyrophosphate, TPP, in the brain and liver
by a specific enzyme;-
• thiamin diphosphotransferase.
• TPP is necessary as a cofactor for the;-
• 1-pyruvate dehydrogenase (PDH) and
• 2-α-ketoglutarate dehydrogenase catalyzed
reactions associated with the TCA cycle
• 3-transketolase catalyzed reactions of the pentose
phosphate pathway
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17. Thiamin functions
• -the main function of thiamine is its role in
metabolic reaction acting as co-enzyme for
energy and carbohydrate metabolism
• -its deficiency in tissues affect energy
metabolism and thus affect nerve and cardiac
functions
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18. TPP is necessary as a cofactor for the important
enzyme pyruvate dehydrogenase (PDH),
α-ketoglutarate dehydrogenase and transketolase
• 1-Pyruvate dehydrogenase is the key enzyme
in CHO metabolism to complete oxidation (via
the TCA cycle)
• TPP participate in catalyzing oxidative
decarboxylation of pyruvate, to form acetyl-
CoA in citric acid cycle, where a carboxyl group
is removed from a compound and released as
CO2.
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19. An example is the conversion of pyruvate to acetyl-
CoA, which is irreversible, during CHO metabolism
• Oxidative decarboxylation reactions are
oxidation reactions in which a carboxylic
group is removed, forming CO2
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20. • 2-α-ketoglutarate dehydrogenase -thiamine
involved in decarboxylation of alph
ketoglutrate to succinate in krebs cycle by the
emzyme α-ketoglutarate dehydrogenase
• -deficiency of thiamine lead to accumulation
of pyruvate in the blood thus affect peripheral
nervous system and heart
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21. • 3-transketolase; catalyzed reactions of the
pentose phosphate pathway
• oxidative phase, NADPH is generated when
glucose 6-phosphate is oxidized to ribose 5-
phosphate.
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22. deficiency of thiamin
• -two different diseases may result as
deficiency of thiamin
• 1-Beri Beri (wet and dry beri beri) Usually beri
beri diseases result due to long term deficiency
and high intake of carbohydrates
• -Korsakoff syndrome (psychosis)
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23. • Wernicke-Korsakoff syndrome; This disease is most
commonly found in chronic alcoholics due to their poor
dietetic lifestyles.
• Wernicke-Korsakoff syndrome is characterized by
acute encephalopathy (brain dysfunction) followed by
chronic impairment of short-term memory
• - Wet beriberi is associated with mental confusion,
muscular atrophy, edema, tachycardia, caridomegaly
and congestive heart failure in addition to peripheral
neuropathy (is damage to nerves of the peripheral
nervous system
• - Dry beriberi is characterized principally by
peripheral neuropathy. Muscle become waste and week,
difficult walking, patient become bedridden and may
die.
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24. Riboflavin, vitamin B2
• Active form of riboflavin is Riboflavin Phosphate
• It is the central component of the cofactor FAD and
FMN, and therefore required for energy metabolism
• vitamin B2 is required for a wide variety of cellular
processes transferring oxygen from plasma to the
tissues.
• It plays a key role in energy metabolism, and for the
metabolism of fats, ketone bodies, carbohydrates and
proteins.
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25. • Vitamin B2, or riboflavin is an intermediary
the transfer of electrons in the cellular
oxidation-reduction reactions which generate
energy from protein, carbohydrate and fat.
The riboflavin coenzymes are also important
for the transformation of vitamin B6 and folic
acid into their respective active forms, and for
the conversion of tryptophan into niacin.
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26. Riboflavin structure
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27. Structure of FAD
Riboflavin is the precursor for the coenzymes, flavin
mononucleotide (FMN) and flavin adenine dinucleotide
(FAD), used to oxidized substrates.
FAD contains riboflavin and adenine.
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28. The enzymes that require FMN or FAD as cofactors are
termed flavoproteins.
During the enzymatic reactions involving the
flavoproteins the reduced forms of FMN and FAD are
formed, FMNH2 and FADH2, respectively.
The hydrogens of FADH2 are on nitrogen 1 and 5
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29. • Synthesis of these two cofactors occurs in a
two step process.
• 1-FMN is synthesized from riboflavin via the
ATP-dependent enzyme riboflavin kinase
(RFK).
• RFK introduces a phosphate group onto the
terminal hydroxyl of riboflavin.
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30. • 2-FMN is then converted to FAD via the
attachment of AMP (derived from ATP) though
the action of FAD pyrophosphorylase
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31. Deficiency of riboflavin
• In humans, signs and symptoms of riboflavin
deficiency
• -include cracked and red lips, inflammation of the
lining of mouth and tongue, mouth ulcers, cracks
at the corners of the mouth (Angular cheilitis),
and a sore throat.
• -A deficiency may also cause dry and scaling
skin, fluid in the mucous membranes, and iron-
deficiency anemia. The eyes may also become
bloodshot, itchy, watery and sensitive to bright
light.
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32. Riboflavin Deficiency
Riboflavin Deficiency Riboflavin Deficiency
(Cheilosis) (Glossitis
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33. Niacin Vitamin B3
nicotinic acid, nicotinamide, niacinamide
• Niacin (nicotinic acid and nicotinamide) is also
known as vitamin B3.
• Both nicotinic acid and nicotinamide can
serve as the dietary source of vitamin B3.
• Niacin is required for the synthesis of the
active forms of vitamin B3, nicotinamide
adenine dinucleotide (NAD+) and nicotinamide
adenine dinucleotide phosphate (NADP+).
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34. Nicotinic acid
formula C5H4NCO2H
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35. Dr. Siham Gritly 35

36. • NADH, NAD+, NADP+ and NADPH which
are coenzymes found in all living cells.
• NAD+ and NADP+ are oxidizing agents.(loss
of electron)
• NADH and NADPH are reducing agents.(gain
of electron)
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37. Important co-enzymes
Niacin is the main components of important
two Co- enzymes
1-nicotin-amide Dinucleotide (NAD)
2-nicotin-amide Adenin Dinucleotide
Act as co-enzyme for reactions involved
dehydrogenase enzymes
Main function act as electron transport and
hydrogen carrier involved in fats,
carbohydrates and protein metabolism
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38. nicotinamide adenine dinucleotide (NAD+)
NAD+ is capable of carrying and transferring
electrons and functions as oxidizing agent in redox
reactions
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39. Oxidoreduction: Pyridine nucleotide coenzymes
(NAD+/NADP+) (Vitamin B3, Niacin)
NAD+/NADH; NADP+/NADPH
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40. Niacin functions
Role of NAD+ in oxidation-reduction reactions
1-reaction of transport hydrogen atom from one
part to another, occur in mitochondria and
cytoplasm of the cells –oxidative reactions of
NAD------NADH
*glycolysis -------glyceraldehyde 3P to 1,3
diphosphglycerate
*oxidative decarboxylation of pyruvate to lactate
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41. oxydation of acetyl Co A in TCA cycle
-malate to oxaloacetate
-glutamate to α ketoglutrate
*β oxidation of fatty acid
2-NAD----dehydrogenase for catabolism of
vitamin B6 pyridoxal to its excretory product
(pyridoxin acid)
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42. 3-NADPH (reduced form) involved in;
Fatty acid synthesis
Cholesterol synthesis
Deoxy-ribonucleotide molecules (DNA)
4-NADPH--- convert folate to dihydrofolate
(DHF) and synthesis of 5 methyl-
tetrahydrofolate the active form of folic acid
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43. niacin deficiency
• Severe deficiency of niacin in the diet causes the
disease pellagra characterized by three Ds;
Diarrhea, loss of fluids
Dermatitis, hyperpigmentation, thickening of the
skin, inflammation of the mouth and
tongue, digestive disturbances,
Dementia, (mental symptoms) such as irritability, poor
concentration, anxiety, fatigue, restlessness, apathy, a
nd depression Dr. Siham Gritly 43

44. pellagra
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45. Pyridoxine
vitamin B6
• Pyridoxal,
• pyridoxamine
• Pyridoxine
• are collectively known as vitamin B6.
• The three forms equal vital activities in their
active forms
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46. • All three compounds are efficiently converted
to the biologically active form of vitamin B6,
pyridoxal phosphate (PLP).
• -pyridoxal phosphate
• -pyridoxine phosphate
• -pyridoxamine phosphate
• This conversion is catalyzed by the ATP
requiring enzyme, pyridoxal kinase.
• Pyridoxal kinase requires zinc for full activity
thus making it a metaloenzyme.
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47. Pyridoxine structure
It is based on a pyridine ring, with
hydroxyl, methyl, and hydroxymethyl
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48. Pyridoxal
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49. Pyridoxamine
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50. Pyridoxal phosphate; the active form of B6
Vitamin B6 is precursor to coenzyme pyridoxal phosphate (PLP)
which is required in certain transformation of amino acids
including transamination, deamination, and decarboxylation.
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51. • Pyridoxal phosphate functions as a cofactor in
enzymes involved in transamination reactions
required for the synthesis and catabolism of
the amino acids
• Act as co-enzyme needed in amino acid
metabolism such as conversion of essential
amino acid tryptophan to vitamin niacin
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52. • Also it function in glycogenolysis as a cofactor for
glycogen phosphorylase
• Vitamin B6 is involved in over 100 metabolic reactions
in the body, including the production of energy and
hemoglobin, a protein in red blood cells. Intakes below
the DRI can hurt performance.
• Deficiencies of vitamin B6 are rare and usually are
related to an overall deficiency of all the B-complex
vitamins
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53. Pantothenic acid
• Pantothenic acid is used in the synthesis of co-
enzyme A (CoA).
• This coenzyme is formed when the vitamin
combines with a derivative of ADP and the amino
acid cysteine.
• Coenzyme A may act as an acyl group carrier to
form acetyl-CoA and other related compounds;
this is a way to transport carbon atoms within the
cell.
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54. • CoA is also important in the biosynthesis of
many important compounds such as fatty
acids, cholesterol.
• CoA is important in energy metabolism for
pyruvate to enter the Kerbs cycle or
tricarboxylic acid cycle (TCA cycle) as acetyl-
CoA,
• and for α-ketoglutarate to be transformed to
succinyl-CoA in the cycle.
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55. Co A
A coenzyme is a small, organic, non-protein molecules
that carries chemical groups between enzymes
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56. Acetyle co A
Acetyl –contain methyl group bonded to carbonyl
The carbonyl center of an acyl radical has one
nonbonded electron with which it forms a chemical
bond to the remainder R of the molecule.
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57. Deficiency of Pantothenic Acid
• deficiency of pantothenic acid in rats leads to
elevated serum concentrations of triglycerides
and non-esterified fatty acids, reflecting
impaired β- oxidation.
• with B-oxidation would have an effect on fat
use. Co-A is also necessary in CHO
metabolism, as it is a part of acetyl-CoA
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58. Folic acid
• The folates are a group of heterocyclic compounds
consisting of a pteridine ring structure linked to para-
aminobenzoic acid (PABA) that forms pteroic acid.
• Pteridine is a group of organic compounds having
two fused six-member rings each containing two
nitrogen atoms and four carbon atoms.
• One of the rings is a pyrimidine, the other a pyrazine.
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59. • Pyrazine, a group of organic compounds
having a six-member ring in which the first
and fourth atoms are nitrogen and the rest are
carbon
pyrimidine, and pyrazine
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60. • The chemical structures of folic acid consist of
three ringed structures plus one or more
molecules of the amino acid glutamate (or
glutamic acid).
The number of glutamate molecules affects the
absorption and metabolism of folate or folic
acid in the body.
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61. active form of folic acid is tetrahydrofolate
Chemical structure of THF. The N5 and N10-nitrogen atoms
that can carry one-carbon functional groups
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62. Folic acid structure
positions 7 and 8 carry hydrogens in dihydrofolate (DHF)
positions 5–8 carry hydrogens in tetrahydrofolate (THF)
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63. • Folic acid is reduced within cells (principally
the liver where it is stored) to tetrahydrofolate
(THF also H4folate) through the action of
dihydrofolate reductase (DHFR), an NADPH-
requiring enzyme.
• When stored in the liver or ingested folic acid
exists in a polyglutamate form
• Polyglutamate is the storage form of folic acid
in the liver
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64. • Deficiency causes megaloblastic anemia as for
vitamin B12 deficiency.
• The inability to synthesize DNA during
erythrocyte maturation leads to abnormally
large erythrocytes termed macrocytic anemia
• Folic acid is important in preventing
neuraltube defects (NTDs) in the developing
human fetus.
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65. Vitamin B12 cyanocobalamin
• Vitamin B12 is the name for a class of related
compounds that have the vitamin activity. These
compounds contain the rare element cobalt.
• Humans can not synthesis B12 and must obtain it from
diet. Enzymes that catalyze certain rearrangement
reaction required B12 or its derivatives.
• Vitamin B12 is synthesized exclusively by
microorganisms and is found in the liver of animals
bound to protein as methycobalamin or 5'-
deoxyadenosylcobalamin.
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66. • The vitamin must be hydrolyzed from protein
in order to be active.
• Hydrolysis occurs in the stomach by gastric acids
or the intestines by trypsin digestion following
consumption of animal meat.
• The vitamin is then bound by intrinsic factor, a
protein secreted by parietal cells of the stomach,
and carried to the ileum where it is absorbed.
• Following absorption the vitamin is transported
to the liver in the blood bound to transcobalamin
II.
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67. There are only two clinically significant reactions in
the body that require vitamin B12 as a cofactor.
• 1- During the catabolism of fatty acids with an
odd number of carbon atoms and the amino acids
valine, isoleucine and threonine the resultant
propionyl-CoA is converted to succinyl-CoA for
oxidation in the TCA cycle.
• 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.
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68. • 2-The second reaction requiring vitamin B12
catalyzes the conversion of homocysteine to
methionine and is catalyzed by methionine
synthase.
• This reaction results in the transfer of the
methyl group from N5-methyltetrahydrofolate
to hydroxycobalamin generating
tetrahydrofolate (THF) and methylcobalamin
during the process of the conversion
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69. Pyrrole is a heterocyclic aromatic organic compound, a five-
membered ring with the formula C4H4NH
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70. Vitamin B12 is composed of a complex tetrapyrrol ring
structure (corrin ring) and a cobalt ion in the center.
Tetrapyrroles are compounds containing four pyrrole rings
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71. Dr. Siham Gritly 71

72. Deficiencies of B12
• The liver can store up to six years vitamin
B12, therefore deficiencies in this vitamin are rare.
• Pernicious anemia is a megaloblastic anemia
resulting from vitamin B12 deficiency that
develops as a result a lack of intrinsic factor in the
stomach leading to malabsorption of the vitamin.
• The anemia results from impaired DNA synthesis
due to a block in purines and thymidine
biothynthesis.
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73. • Pernicious anemia: a blood disorder that
reflects a vitamin B12 deficiency caused by
lack of intrinsic factor and characterized by
abnormally large and immature red blood
cells. Other symptoms include muscle
weakness and irreversible neurological
damage
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74. Biotin
• Biotin, one of the water soluble B-vitamins, occurs in 8
different forms but only one of these, D-biotin, is found
in nature and has full vitamin activity
• It is water soluble and important in the metabolism of
fatty acids and the amino acid Leucine
• Biotin in its coenzyme form participates in numerous
reactions involved in the metabolism of fat and CHO
• involved in carboxylation reactions, e.g. acetyl-CoA
carboxylase and pyruvate carboxylase.
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75. • participates in the entry of certain carbon
skeletons from amino acids into the energy-
yielding pathways, as well as in DNA synthesis.
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76. Biotin structure
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77. • Biotin is found in numerous foods and also is
synthesized by intestinal bacteria and as such
deficiencies of the vitamin are rare.
• Deficiencies are generally seen only after long
antibiotic therapies which deplete the intestinal
fauna or following excessive consumption of raw
eggs.
• The latter is due to the affinity of the egg white
protein, avidin, for biotin preventing intestinal
absorption of the biotin.
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78. Deficiency is rare, but can result in:Anorexia Nausea
Vomiting Dermatitis
• Symptoms that may appear if biotin is deficient
are extreme exhaustion, drowsiness, muscle
pain, loss of appetite, depression, and grayish skin
color.
• Some of the richest sources of biotin are
tomatoes, romaine lettuce, and carrots. Additional
sources include
onions, cabbage, cucumber, cauliflower, mushroo
ms, peanuts, almonds, walnuts, oat
meal, bananas, raspberries, strawberries, soy, egg
yolk, and cow and goat milk.
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79. Vitamin C
Ascorbic Acid
• Vitamin C is found in most plants and animals
• it is an essential in many biosynthetic pathways such as
synthesizing collagen.
• Deficiency leads to a disease called Scurvy.
• Vitamin C helps regulate the immune system and relieve
pain caused by tired muscles.
• It also is needed in the manufacture of collagen and
norepinephrine.
• Vitamin C is also an antioxidant which can enhance the
immune system by stimulating white blood cells in the
body.
• Vitamin C also helps to benefit the skin, teeth, and bones.
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80. Ascorbic Acid structure
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81. Examples of Coenzymes and Vitamins
reference; Cooper GM; The Central Role of Enzymes as
BiologicalCatalysts The Cell: A Molecular Approach. 2nd edition
Coenzyme Related vitamin Chemical reaction
NAD+, NADP+ Niacin Oxidation-reduction
FAD Riboflavin (B2) Oxidation-reduction
Thiamine Thiamine (B1) Aldehyde group
pyrophosphate transfer
Coenzyme A Pantothenate Acyl group transfer
Tetrahydrofolate Folate Transfer of one-
carbon groups
Biotin Biotin Carboxylation
Pyridoxal Pyridoxal (B6) Transamination
phosphate Dr. Siham Gritly 81

82. Fat soluble vitamins
• Fat soluble vitamins dissolve within the body’s fat
cells and are usually found in fats and fatty foods.
• If they are not needed immediately, the body will
store fat soluble vitamins for later use in the liver
and fatty tissues
• fat soluble vitamins do not need to be consumed
as frequently as water soluble vitamins to ensure
proper functioning of the body’s cells.
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83. Vitamin A
• Vitamin A consists of three biologically active
molecules,
• 1-retinol, (hydroxyl) involved in vision
• 2- retinal (aldehyde) involved in vision
• 3-retinoic acid. (carboxyl) for cellular
differentiation (regulate gene expression)
• Each of these compounds are derived from the
plant precursor molecule, β-carotene (a member
of a family of molecules known as carotenoids).
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84. • Beta-carotene, which consists of two molecules
of retinal linked at their aldehyde ends, is also
referred to as the provitamin form of vitamin A.
• Vitamin A is found in dark green and yellow
vegetables and yellow fruits, such as broccoli,
spinach, turnip greens, carrots, squash, sweet
potatoes, pumpkin, cantaloupe, and apricots, and
in animal sources such as liver, milk, butter,
cheese, and whole eggs.
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85. Structure of vitamin A consist of a single6-membered
ring to which is attached an 11-carbon side chain
Beta-carotene consist of two molecules of
retinal linked at their aldehyde ends
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86. Absorption, transport and storage
• Ingested β-carotene is cleaved in the lumen of the
intestine by β-carotene dioxygenase to yield
retinal.
• Retinal is reduced to retinol by retinaldehyde
reductase, an NADPH requiring enzyme within
the intestines.
• Retinol is esterified to palmitic acid and delivered
to the blood via chylomicrons. The uptake of
chylomicron by the liver results in delivery of
retinol to this organ for storage as a lipid ester
within lipocytes (adipose tissues).
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87. • Transport of retinol from the liver to extrahepatic
tissues occurs by binding of hydrolyzed retinol to
aporetinol binding protein (RBP).
• the retinol-RBP complex is then transported to
the cell surface within the Golgi and secreted.
Within extrahepatic tissues retinol is bound to
cellular retinol binding protein (CRBP).
• Plasma transport of retinoic acid is accomplished
by binding to albumin
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88. Vitamin A functioning as vitamin and hormone
• retinol and retinoic acid with in the cell bind to
specific receptor present in the nucleolus of
tissues
• This receptor-vitamin complex interact with
several genes that involved in growth and cell
differentiation thus affect expression of genes
• cell differentiation is the process by which
immature cells develop specific functions
different from those of the original that are
characteristic of their mature cell type.
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89. Vision and Vitamin A
• the process of vitamin A in vision known as
Rhodopsin cycle or Ward’s visual cycle the
• Photoreception in the eye is the function of
two specialized cell types located in the retina;
• Rods
• Cones
• Both rod and cone cells located in the retina
contain a photoreceptor pigment in their
membranes and vitamin A is a component of
these pigments
Dr. Siham Gritly 89

90. • the rod;- The opsin of rod cells is called
Rhodopsin (visual purple) consist of 11-cis retinal
bound to protein opsin (vision in dim light)
• Rhodopsin absorbs light, 11-cis retinal is
converted to all trans retinal
• The isomerization act on the conformation change
in the protein opsin
• This process lead to generate nerve impulse that
transmitted to brain through the optic nerve
Dr. Siham Gritly 90

91. • This is followed by dissociation of the trans
retinal from opsin
• The trans retinal is immediately isomerised by
the enzyme isomerase to 11-cis retinal
• 11-cis retinal combines with opsin to
regenerate rhodopsin and complete the vision
cycle
Dr. Siham Gritly 91

92. • cone cells, contain colour pigments,
*porphyropsin (red)
• *Iodopsin (green)
• *Cyanopsin (blue)
• The pigments are converted to trans retinal and
the protein opsin is released
• The reaction stimulate the nerve impulse thus
the brain red the colour
Dr. Siham Gritly 92

93. cis-retinal, the hydrogens (light gray in the molecular model on
the left) are on the same side of the double bond (yellow in the
molecular model). In the trans-retinal, the hydrogens are on
opposite sides of the double bond. In fact, all of the double
bonds are in the trans-configuration in this isomer: the
hydrogens, or hydrogen and -CH3, are always on opposite sides
of the double bonds
Dr. Siham Gritly 93

94. Dr. Siham Gritly 94

95. Vitamin A Deficiency
• Vitamin A is stored in the liver and deficiency of
the vitamin occurs only after prolonged lack of
dietary intake.
• The earliest symptoms of vitamin A deficiency
are night blindness.
• Additional early symptoms include follicular
hyperkeratinosis, increased susceptibility to
infection and cancer and anemia equivalent to
iron deficient anemia.
• Prolonged lack of vitamin A leads to
deterioration of the eye tissue through progressive
keratinization of the cornea, a condition known as
xerophthalmia.
Dr. Siham Gritly 95

96. The earliest symptoms of vitamin A deficiency ;-
*impaired dark adaptation –night blindness (nyctalopia)
*poor vision in dim light
*xerophthalmia
The first stage of xerophthalmia is conjunctival xerosis
Later Bitot’s spots form (keratinization of epithelial
cells)
A deficiency progresses degenerative changes of retina
occurs (keratomalcia)
Ulceration and necrosis developed in the cornea that
lead to blindness
Dr. Siham Gritly 96

97. Xerophthalmia
Xerophthalmia is a severe drying of the eye surface caused by
a malfunction of the tear glands.
it occurs most commonly because of decreased intake or
absorption of vitamin A. Symptoms include night blindness
and eye irritation.
Dr. Siham Gritly 97

98. Ulceration and necrosis developed in the cornea
that lead to blindness
Dr. Siham Gritly 98

99. Vitamin D cholecalciferol
• Vitamin D is known as the sunshine vitamin
because exposure to sunlight prompt the
body’s cells to start producing it.
• Vitamin D2 functions as a steroid hormone and
vitamin
• regulate calcium and phosphorous homeostasis
• Apart from sunlight, dairy products (such as
eggs, milk and butter), fatty fish and fish oils
are all good sources of vitamin D.
Dr. Siham Gritly 99

100. • Vitamin D comes in many forms, but the two
most important in the diet are;-
• 1-plant sterol ergosterol which isolated from
plant and by commercial irradiation ligh UV
coverted to vitamin D2 or ergocalciferol
• 2-animal sources or naturally produced called
vitamin D3 or cholecalciferol.
Dr. Siham Gritly 100

101. Vitamin D2 and Vitamin D3
a group of steroid compound
Vitamin D2 Vitamin D3
ergocalciferol cholecalciferol.
Dr. Siham Gritly 101

102. Formation of vitamin D3 in the skin
• The naturally found vitamin D3 cholecalciferol is
the form obtained either from animal sources or
made in the skin by the action of ultraviolet light
from the sun on 7-dehydrocholesterol
• 7-dehydrocholesterol found in animal tissues
synthesized in the sebaceous glands of the skin
and secreted into the skin surface
• During exposure to sunlight 7-dehydrocholesterol
forming pre-cholecalcefirol (previtamin D3)
Dr. Siham Gritly 102

103. 7-Dehydrocholesterol and Ergosterol
structures
7-Dehydrocholesterol;
accumulates in the skin
Ergosterol previtamin
By sunlight converted to D2 found in plant foods
cholecalciferol not found in human
tissues
Dr. Siham Gritly 103

104. Active form of the hormone
1,25-dihydroxycholecalciferol
• The biologically active form of the hormone is
1,25-dihydroxy vitamin D3 (1,25-(OH)2D3, also
called 1,25-dihydroxycholecalciferol or
calcitriol).
Dr. Siham Gritly 104

105. activation of vitamin D must be achieved
through;
• 1-Liver
• 2-kidneys
• In the Liver;- cholecalciferol fuses into the blood
carried by D-binding protein (DBP) known as
transcalciferin to the liver
• By the action of liver enzyme 25-hydroxylase
hydroxylate cholecaciferol at carbon 25 to form 25-
OH cholecalciferol/D3
• The activity of this enzyme related to the
concentration of vitamin D
• 25-hydroxylase also found in lungs, intestine and
Dr. Siham Gritly 105
kidneys

106. 25-hydroxyvitamin D3
in the liver enzyme 25-hydroxylase hydroxylate
cholecaciferol at carbon 25 to form 25-OH
cholecalciferol/D3
Dr. Siham Gritly 106

107. • In the kidneys;-a second hydroxylation of 25-OH
D3 (25-hydroxylcalcefirol) occur at position 1
• by the action of enzyme 1-hydroxylase in the
kidnyes, 25-cholecalsiferol hydrolyized to
1,25-(OH)2 cholecalecalciferol or known as
(calcitriol ) the active form of vitamin D
• By the transporter DBP which is the majour
protein in the blood transported the active form
calcitriol (1,25-(OH)2 cholecalciferol) to the
target tissues
Dr. Siham Gritly 107

108. • The activity of 1-hydroxylase is influenced by
• -parathyroid hormone
• -low plasma concentration
• -The concentration of 1,25
hydoxycholecaciferol- high concentration
inhibit the enzyme activity,- low concentration
stimulate it
• Low intake of phosphours
Dr. Siham Gritly 108

109. 1,25-dihydroxyvitamin D3
by the action of enzyme 1-hydroxylase in the kidnyes, 25-
cholecalsiferol hydrolyized to 1,25-(OH)2 cholecalecalciferol
active form of vitamin D
Dr. Siham Gritly 109

110. • 25-(OH)D3 can also be hydroxylated at the 24
position by a specific D3-24-hydroxylase in the
kidneys, intestine, placenta and cartilage
Dr. Siham Gritly 110

111. 1,25-dihydroxcholecaliciferol D3 formation
Tissue cholesterol
↓
Sun
↓
7-dehydrocholesterol
Plasma
Cholecaliciferol D3
↓
liver
25-hydroxycholecaliciferol
↓
kidneys
1,25-dihydroxycholecaliciferol → target tissue
Dr. Siham Gritly 111

112. deficiency results in harmful changes in bone, a condition
known as rickets in children and osteomalacia in adults.
Vitamin D–Deficiency Symptoms—Bowed Legs and Beaded
Ribs of Rickets
Dr. Siham Gritly 112

113. • Osteoporosis Any failure to synthesize
adequate vitamin D or obtain enough
• from foods sets the stage for a loss of calcium
from the bones, which can result
• in fractures. Highlight 12 describes the many
factors that lead to osteoporosis, a
• condition of reduced bone density.
Dr. Siham Gritly 113

114. Vitamin E tocopherol
• Vitamin E is an antioxidant a substance that that
stops chain reactions caused by free radicals that
can damage cells and affect its normal
physiological function .
• free radicals: is an unstable and highly reactive
atoms or molecules that have one or more
unpaired electrons in the outer orbital
• Vitamin E acts primarily in lipid-rich areas of the
body, where free radicals can initiate a chain of
reactions known as peroxidation.
Dr. Siham Gritly 114

115. • peroxidation is a type of reaction in which
oxygen atoms are formed leading to the
production of peroxides. It is stimulated in the
body by certain toxins and infections
• Lipid peroxidation reactions break apart fatty
acids and create free radicals called lipid
peroxyl radicals (also called reactive oxygen
species because they contain oxygen radicals).
Dr. Siham Gritly 115

116. • The most concern free radicals in biological
systems are derived from oxygen, Example of
free radicals;- Superoxide radical (O2.- ),
Hydrogen peroxide (H2O2), Hydroxyl radical
(.OH) and others such as Nitric oxide (.NO)
and others
• Read more about free radicals
Dr. Siham Gritly 116

117. • In addition to vitamin E, the body has various
other antioxidant compounds, such as
glutathione peroxidase, catalase, superoxide
dismutase, to protect against oxidative
damage.
Dr. Siham Gritly 117

118. Alpha-Tocopherol structure
alcoholic hydroxyl group and a 12-carbon aliphatic side
chain containing two methyl groups in the middle and
two more methyl groups at the end
the side chain is saturated
Dr. Siham Gritly 118

119. Vitamin K
phylloquinone
• The K vitamins exist naturally as;-
• K1 (phylloquinone) in green vegetables
• K2 (menaquinone) produced by intestinal bacteria
• K3 is synthetic menadione.
• Vitamin K is needed for the process of clotting of
blood and Ca2+ binding. Vitamin K can be
synthesized by bacteria in the intestines. Vitamin
K is needed for catalyzing the carboxylation of
the γ-carbon of the glutamate side chain in
proteins.
Dr. Siham Gritly 119

120. Vitamin K
phylloquinone and menaquinone share a
methylated ring structure
Dr. Siham Gritly 120

121. • Vitamin K’s main function is to help the blood
clot but it also assists with calcium retention in
the body.
• Vitamin K contributes to the body’s blood-
clotting ability by facilitating the conversion of
precursor proteins, such as prothrombin, to
active clotting factors thrombin that promote
blood coagulation.
Dr. Siham Gritly 121

122. • Green leafy vegetables (such as
spinach, broccoli and cabbage) are rich in
vitamin K but eggs and milk also contain
lower levels of the vitamin.
• Deficiency can be very serious and cause
heavy, uncontrolled bleeding in multiple areas
of the body. consuming too much vitamin K
can damage both blood cells and liver.
Dr. Siham Gritly 122

123. Dr. Siham Gritly 123

124. Vitamins that are Cofactor
& coenzyme Precursors
Chemical
Additional
Cofactor Vitamin group(s) Distribution
component
transferred
Thiamine 2-carbon Bacteria,
pyrophosphate Thiamine (B1) None groups, α archaea and
[24] cleavage eukaryotes
Bacteria,
NAD+ and
Niacin (B3) ADP Electrons archaea and
NADP+ [25]
eukaryotes
Bacteria,
Pyridoxal Amino and
Pyridoxine (B6) None archaea and
phosphate [26] carboxyl groups
eukaryotes
Bacteria,
electrons, acyl
Lipoamide [3] Lipoic acid None archaea and
groups
eukaryotes
Bacteria,
Methylcobalam Dr. Siham Gritly 124
Vitamin B12 Methyl group acyl groups archaea and
in [27]

125. Bacteria,
Cobalamine hydrogen, alkyl
Cobalamine [3] None archaea and
(B12) groups
eukaryotes
Bacteria,
Biotin [28] Biotin (H) None CO2 archaea and
eukaryotes
Acetyl group Bacteria,
Pantothenic
Coenzyme A [29] ADP and other acyl archaea and
acid (B5)
groups eukaryotes
Methyl, formyl,
Bacteria,
Tetrahydrofolic Glutamate methylene and
Folic acid (B9) archaea and
acid [30] residues formimino
eukaryotes
groups
Dr. Siham Gritly 125

126. Bacteria,
Menaquinone Carbonyl group
[31] Vitamin K None archaea and
and electrons
eukaryotes
Bacteria,
Ascorbic acid
[32] Vitamin C None Electrons archaea and
eukaryotes
Flavin Bacteria,
mononucleotid Riboflavin (B2) None Electrons archaea and
e [33] eukaryotes
Bacteria,
Flavin adenine
Riboflavin (B2) None Electrons archaea and
dinucleotide [33]
eukaryotes
Coenzyme
Riboflavin (B2) Amino acids Electrons
F420 [34]
Dr. Siham Gritly 126

127. • Murry K. Robert, Granner K. daryl, Mayes A. peter, Rodwell W. Victor (1999). Harpers Biochemistry. Appleton and
Lange , twent fifth edition
• Campbell, Neil A.; Brad Williamson; Robin J. Heyden (2006). Biology: Exploring Life. Boston, Massachusetts:
Pearson Prentice Hall
• A. Burtis, Edward R. Ashwood, Norbert W. Tietz (2000), Tietz fundamentals of clinical chemistry
• Maton, Anthea; Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryanna Quon Warner, David
LaHart, Jill D. Wright (1993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. pp.
52–59
• Maitland, Jr Jones (1998). Organic Chemistry. W W Norton & Co Inc (Np). p. 139. ISBN 0-393-97378-6.
• Nelson DL, Cox MM (2005). Lehninger's Principles of Biochemistry (4th ed.). New York, New York: W. H.
Freeman and Company.
• Matthews, C. E.; K. E. Van Holde; K. G. Ahern (1999) Biochemistry. 3rd edition. Benjamin Cummings.
• http://wiki.answers.com/Q/What_is_dehydration_synthesis#ixzz2BuiK645
Dr. Siham Gritly 127

128. • D. Voet, J. G. Voet, Biochemistry, second edition ed., John Wiley &
• Sons, New York, 1995
• Sareen Gropper, Jack Smith and James Groff, Advanced Nutrition and Human Metabolism, fifth ed.
WADSWORTH
• Melvin H Williams 2010; Nutrition for Health, Fitness and Sport. 9th ed, McGraw Hill
•
• Heymsfield, SB.; Baumgartner N.; Richard and Sheau-Fang P. 1999. Modern Nutrition in Health and Disease;
Shils E Maurice, Olson A. James, Shike Moshe and Ross A. Catharine eds. 9th edition
• Guyton, C. Arthur. 1985. Textbook of Medical Physiology. 6th edition, W.B. Company
• Lehninger. Principles of bochemistry. by Nelson and Cox, 5th Edition; W.H. Freeman and Company
• Emsley, John (2011). Nature's Building Blocks: An A-Z Guide to the Elements (New ed.). New York, NY: Oxford
University Press. ISBN 978-0-19-960563-7.
• Koppenol, W. H. (2002). "Naming of New Elements (IUPAC Recommendations 2002)" (PDF). Pure and Applied
Chemistry 74 (5): 787–791. doi:10.1351/pac200274050787.
http://media.iupac.org/publications/pac/2002/pdf/7405x0787.pdf.
•
http://www.differencebetween.com/difference-between-acyl-and-vs-acetyl/#ixzz2HmrSvksL
Dr. Siham Gritly 128

129. • acyl group is characterized by a carbon and oxygen
atom, which is linked by a double bond. Identifying an
acyl group is easy because of the C=O part.
• Acetyl group is a common example for an organic acyl
group. This is also known as ethanoyl group. It has the
chemical formula of CH3CO. Therefore, the R group in
the acyl is replaced by a methyl group. Other bond in
the carbon can be with a –OH, -NH2, -X,-R,-H etc. For
example, CH3COOH is known as acetic acid. The
introduction of an acetyl group into a molecule is
called acetylation.
Dr. Siham Gritly 129