physiological roles of Vitamins
Prepared by;
Dr. Siham Gritly
Dr. Siham Gritly 1

glossary
• 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
Dr. Siham Gritly 2

• 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
Dr. Siham Gritly 3

• 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.
• antioxidant: a substance that signifi cantly decreases the
adverse effects of free radicals on normal physiological
functions
Dr. Siham Gritly 4

Vitamins
• Vitamins are organic molecules needed for variety of
biological function within the body.
• The most important role 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).
Dr. Siham Gritly 5

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.
Dr. Siham Gritly 6

• 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
Dr. Siham Gritly 7

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
Dr. Siham Gritly 8

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
Dr. Siham Gritly 9

• -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
Dr. Siham Gritly 10

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
Dr. Siham Gritly 11

• 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).
Dr. Siham Gritly 12

• 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
Dr. Siham Gritly 13

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
Dr. Siham Gritly 14

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.
Dr. Siham Gritly 15

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
Dr. Siham Gritly 16

• 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
Dr. Siham Gritly 17

• 3-transketolase; catalyzed reactions of the
pentose phosphate pathway
• oxidative phase, NADPH is generated when
glucose 6-phosphate is oxidized to ribose 5-
phosphate.
Dr. Siham Gritly 18

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)
Dr. Siham Gritly 19

• 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
Dr. Siham Gritly 20

• - 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.
Dr. Siham Gritly 21

Beriberi is a disease caused by a deficiency of thiamine
(vitamin B1) that affects many systems of the
body, including the muscles, heart, nerves, and digestive
system
Dr. Siham Gritly 22

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.
Dr. Siham Gritly 23

• 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 FAD
and FMN.
• 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.
Dr. Siham Gritly 24

• 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.
Dr. Siham Gritly 25

• 2-FMN is then converted to FAD via the
attachment of AMP (derived from ATP) though
the action of FAD pyrophosphorylase
Dr. Siham Gritly 26

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.
Dr. Siham Gritly 27

Riboflavin Deficiency
Riboflavin Deficiency Riboflavin Deficiency
(Cheilosis) (Glossitis
Dr. Siham Gritly 28

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+).
Dr. Siham Gritly 29

• 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)
reactions involved dehydrogenase enzymes
electron transport and hydrogen carrier involved
in fats, carbohydrates and protein metabolism
Dr. Siham Gritly 30

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
Dr. Siham Gritly 31

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)
Dr. Siham Gritly 32

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
Dr. Siham Gritly 33

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 34

Pellagra
niacin deficiency
Dr. Siham Gritly 35

Pellagra
niacin deficiency
Dr. Siham Gritly 36

Pyridoxine
vitamin B6
• Pyridoxal,
• pyridoxamine
• Pyridoxine
• are collectively known as vitamin B6.
• The three forms equal vital activities in their
active forms
• found in different types of food such as; Wheat
germ, Sunflower seeds, Dry
Soybeans, Walnuts, Soybean flour Lentils Brown
rice peas Bananas, Chicken, white fish, Potatoes
Dr. Siham Gritly 37

• 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.
Dr. Siham Gritly 38

• 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
Dr. Siham Gritly 39

• 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
Dr. Siham Gritly 40

• Factors which reduce Vitamin B6 absorption
• Exposure of Vitamin B6 containing foods to
ultraviolet light
• Cooking
• Exposure to alkaline pH
• Food processing destroys up to 90% of
Vitamin B6 content in food
Dr. Siham Gritly 41

• Factors which increase Vitamin B6 excretion
• Smoking
• Excess alcohol
• Excessive tea /coffee caffeinated drinks
consumption
• Use of hormonal contraception
• Use of drugs such as diuretics,
• Excessive protein consumption
Dr. Siham Gritly 42

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.
Dr. Siham Gritly 43

• 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.
Dr. Siham Gritly 44

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
Dr. Siham Gritly 45

Folic acid
(pteroylglutamic 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.
Dr. Siham Gritly 46

Folic acid (pteroylglutamic acid) is composed of three large sub-
components. 1-pteridine ring,2- para-amino benzoic acid, and 3-
glutamic acid. Glutamic acid is an amino acid that the body can
actually synthesize by itself and is found in proteins. Folic acid
gets its name from the Latin word folium meaning "leaf", since
it's found in many leafy plants.
Dr. Siham Gritly 47

• The number of glutamate molecules affects the
absorption and metabolism of folate or folic
acid in the body.
Dr. Siham Gritly 48

active form of folic acid is tetrahydrofolate
Chemical structure of THF. The N5 and N10-nitrogen
atoms that can carry one-carbon functional groups
Dr. Siham Gritly 49

Pteroylglutamate (folic acid)
Polyglutamate is the storage form of folic acid in the
liver
• 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
Dr. Siham Gritly 50

• 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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megaloblastic macrocytic anemia
Dr. Siham Gritly 52

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.
Dr. Siham Gritly 53

• 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 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.
Dr. Siham Gritly 54

• Vitamin B12 is involved in a number of body
processes, but is mainly;
• formation to red blood cell production,
• nervous system function,
• sperm production,
• normal growth
• the proper function of the immune system.
Dr. Siham Gritly 55

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.
Dr. Siham Gritly 56

• 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
Dr. Siham Gritly 57

Deficiencies of B12
Pernicious anemia is a megaloblastic anemia
resulting from vitamin B12 deficiency
• 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.
Dr. Siham Gritly 58

• Pernicious anemia characterized by
abnormally large and immature red blood
cells.
• Other symptoms include muscle weakness and
irreversible neurological damage
• The anemia results from impaired DNA
synthesis due to a block in purines and
thymidine biothynthesis.
Dr. Siham Gritly 59

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
Dr. Siham Gritly 60

• 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.
• participates in the entry of certain carbon
skeletons from amino acids into the energy-
yielding pathways, as well as in DNA synthesis.
Dr. Siham Gritly 61

• 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.
Dr. Siham Gritly 62

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.
Dr. Siham Gritly 63

Vitamin C Ascorbic Acid
Main physiological roles of vitamin C
• Vital component of all body cells
• Essential for manufacture of collagen, needed
for healthy connective tissue, skin, bones and
vascular system
• Powerful Antioxidant
• Stimulates white blood cells and antibody
production
• Required for proper wound healing and tissue
regeneration
Dr. Siham Gritly 64

• Assists iron absorption
• powerful effects on the production of
important chemicals for the control of
hormones and brain function.
• plays a vital role in the immune system
• It is a key component of collagen
• Vitamin C also helps to benefit the skin, teeth,
and bones.
Dr. Siham Gritly 65

• Deficiency leads to a disease called Scurvy.
• Scurvy is a disease that affects the blood
vessels, skin, and the body’s healing
process, resulting in anemia, hemorrhaging of
the skin, and gum disease (gingivitis).
• Vitamin C is found in most plants and animals
Dr. Siham Gritly 66

• People requiring additional Vitamin C.
• some specific groups who are likely to benefit
more ;
• People with heart disease (angina, heart
attack, "hardened arteries", coronary artery
disease, other vascular disease, high blood
pressure)
• Diabetics
• Those with poorly healing wounds (such as leg
ulcers)
• People with skin problems
Dr. Siham Gritly 67

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 68

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.
Dr. Siham Gritly 69

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)
• Importance 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).
Dr. Siham Gritly 70

• 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.
Dr. Siham Gritly 71

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).
Dr. Siham Gritly 72

• 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
Dr. Siham Gritly 73

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.
Dr. Siham Gritly 74

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 75

• 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 76

• 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 77

• 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 78

Dr. Siham Gritly 79

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 80

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)
Dr. Siham Gritly 81

keratomalcia
Softening and drying and ulceration of the cornea resulting from
vitamin A deficiency developed in the cornea that lead to
blindness
Dr. Siham Gritly 82

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 irritationthe eyes being very dry, there is a loss of luster on
their surface
.
Ulceration and necrosis
developed in the cornea
that lead to blindness
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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
• dairy products (such as eggs, milk and
butter), fatty fish and fish oils are all good
sources of vitamin D.
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Vitamin D comes in many forms, but the two
most important in the diet arel
• 1-plant sterol ergosterol which isolated from
plant and by commercial irradiation light UV
converted to vitamin D2 or ergocalciferol not
found in human tissues
• 2-animal sources or naturally produced called
vitamin D3 or cholecalciferol.
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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)
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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
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kidneys

• In the kidneys;-a second hydroxylation of 25-OH D3
(25-hydroxylcalcefirol) occur at position 1
• by the action of enzyme;-
• 1-hydroxylase, 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 major protein
in the blood transported the active form calcitriol
(1,25-(OH)2 cholecalciferol) to the target tissues
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• Active form of the hormone
The biologically active form of the hormone is;
1,25-dihydroxy vitamin D3 (1,25-(OH)2D3, also
called 1,25-dihydroxycholecalciferol or
calcitriol).
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• 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
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• 25-(OH)D3 can also be hydroxylated at the 24
position by a specific D3-24-hydroxylase in the
kidneys, intestine, placenta and cartilage
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1,25-dihydroxcholecaliciferol D3 formation
Tissue cholesterol
↓
Sun
↓
7-dehydrocholesterol
Plasma
Cholecaliciferol D3
↓
liver
25-hydroxycholecaliciferol
↓
kidneys
1,25-dihydroxycholecaliciferol → target tissue
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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
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• 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.
reduced bone density.
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Vitamin E tocopherol
protect against oxidative damage.
• 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.
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• 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).
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• 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
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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 can be synthesized by bacteria in the
intestines.
• Vitamin K is needed for the process of clotting of blood
and Ca2+ binding.
• Vitamin K is needed for catalyzing the carboxylation of
the γ-carbon of the glutamate side chain in proteins.
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• 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.
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• 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.
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References
• 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
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• 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
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