INTRODUCTION

 Vitamins
 chemically unrelated organic compounds
 cannot be synthesized by humans and
 therefore, must be supplied by the diet
 needed for normal function, growth &maintenance of
normal metabolic integrity
o As cofactors for enzymatic rxn’s
However, Vitamin D & Niacin, do not strictly comply with
this definition
 They are not a source of calories
 Deficiency causes a specific disease
w/c is cured or prevented only by restoring the vitamin to the
diet
 Characteristics of vitamins
 They are organic cpds
 They assist enzymes
 They act in cell multiplication
 They are needed in very small amounts
 They don’t produce energy
 Many vitamins need protein carrier
 They are destructed by
– Oxidation
– Heat
– Light
– storage
 Classification of the Vitamins

4 March 12, 2025

 Water Soluble Vitamins: Characteristics
 Essential
 Organic Structure
 Participate in energy production
 Micronutrients
 Toxicity

 Any excess of these vitamins is

excreted in the urine
 In contrast to the fat-soluble vitamins
No common toxicity associated
with excess of these vitamins ????
 Thiamin (Vitamin B1)

 Structure
 pyrimidine ring
 thiazole ring
Pyrimidine ring methyl Thiazole ring
 methyl bridge
bridge

 Rapidly converted to its

active form:

TPP
Thiamin
active site
diphosphotransferase

in the brain and

 Thiamin cont.
 TPP has a central role in energy-yielding metabolism:
 Especially the metabolism of carbohydrates
 Oxidative decarboxylation rxn’s:
Pyruvate dehydrogenase Pyruvate oxidation
-ketoglutarate dehydrogenase TCA
Branched-chain keto-acid dehydrogenase  Metabol. of
leu, Ile, & Val
Also Coenzyme for Transketolase  HMP
TPP has a role in nerve conduction  in the nerve membrane:
Phosphorylates, & so activates, a chloride channel
 TPP in general serve as coenzyme in
 The formation or degradation of
α-ketols by transketolase
 The oxidative decarboxylation
of α-ketoacids
 Thiamin
Sources

• Pork
• Whole Grain
or Enriched
Grains

 What is the simple reason for the high risk of

deficiency of Thiamin despite the widespread
availability of this vitamin in foods?
 Thiamin… (Cont’d)
 Thiamin deficiency can result in 3 distinct syndromes:

 A chronic peripheral neuritis, beriberi

 Acute pernicious beriberi (shoshin beriberi)
Heart failure & metabolic abnormalities predominate
 Wernicke's encephalopathy with Korsakoff's psychosis,
Mental confusion , ataxia
loss of eye coordination
Wernicke-Korsakoff psychosis
 In deficiency ::The role of TPP in pyruvate dehydrogenase

Impaired conversion of pyruvate to acetyl CoA

May cause life-threatening lactic acidosis
 Riboflavin (Vitamin B2).
 Isoalloxazine Attached to the sugar alcohol  Ribitol
 The molecule is colored, fluorescent
 Decomposes in visible light
 Heat-stable
 Central role in energy-yielding metabolism
 Precursor for the coenzymes:
 Flavin mononucleotide (FMN)
 Flavin adenine dinucleotide (FAD)

 Activation of Riboflavin via ATP-dependent enzyme

system

 FMN  ATP + riboflavin

 FMN is an electron carrier in the ETC
 FADrxn of FMN with ATP
 AMP moiety is transferred to the FMN
 FAD is a cofactor for
 PDC and
 succinate dehydrogenase
Riboflavin
 Riboflavin
Sources

 Milk products
 Yogurt

 Cheese

 Enriched or whole
grains
 Liver
 Deficiency
 Ariboflavinosis - riboflavin deficiency
 Cheliosis - cracks or sores on the outsides of the lips
 Angular stomatitis - cracks or sores of lips at the corners of the mouth
 magenta tongue - inflammation and redness of the tongue
 seborrheic dermatitis- a moist, scaly skin inflammation
 vascularization of the cornea -the formation of blood vessels in the clear
covering of the eye
 Normochromic normocytic anemia -decreased red blood cell count but
normal levels of hemoglobin and are of normal size in the exist
 Niacin (vitamin B3)
Niacin is a generic name for:
 Nicotinic acid or Nicotinamide
 Both can serve as the dietary source of vitamin B3
Required for the synthesis of NAD+ or NADP+
 Participate in oxidoreductase rxn’s(oxidation-redu.
Rxn)
 200 enzymes require NAD+ or NADP+ as a coenzyme
 act as hydrogen donors or
 Involved in energy production
Niacin cont.
Deficiency: Pellagra • Deficiency disease: pellagra
 Dermatitis • Deficiency symptoms
– Diarrhea, abdominal pain, vomiting
– Inflamed, swollen, smooth, bright red tongue
 Dementia 3D – Depression, apathy, fatigue, loss of memory,
 Diarrhea headache…similar to raising some children, or
attending college
 Pantothenic Acid (Vitamin B5)
 Formed from -alanine & pantoic acid
 Has a central role in acyl group metabolism
Acts as a Carrier of Acyl Radicals
Acting as the pantetheine functional moiety of CoA or
ACP
The pantetheine moiety:
formed after combination of Pantothenate with
Cysteine
which provides the –SH prosthetic group of CoA & ACP
 Widely distributed in all food stuffs
 There is no evidence of deficiency in man

18
 Pantothenic
Acid

Coenzyme A
Pantothenic acid & coenzyme
A. -SH Shows the site of acylation by fatty
 Pyridoxine (Vitamin B6 )
 Vitamin B6 is a collective term for
pyridoxine
 pyridoxal derivatives of pyridine
 pyridoxamine
 differ only in the nature of the functional group attached to
the ring
 Pyridoxine occurs  plants
 pyridoxal and pyridoxamine  animals
 All three cpds can serve as precursors of the biologically active
coenzyme
 pyridoxal phosphate.
 Pyridoxal phosphate functions as a coenzyme
Pyridoxine cont.
 Pyridoxine cont.
Reaction type Example
 Transamination - OAA + glutamate ⇔ aspartate + α-ketog
 Deamination - Serine → pyruvate + NH3
 Decarboxylation - Histidine → histamine + CO2
 Condensation - Glycine + succinyl CoA → δ-ALA
Clinical indications for pyridoxine:
• Isoniazid , a drug frequently used to treat tuberculosis
• Can induce a vitamin B6 deficiency by forming an inactive
derivative with pyridoxal phosphate.
• dietary deficiencies in pyridoxine are rare, but
have been observed in newborn
infants fed formulas low in B6
in women taking oral contraceptives, and
in alcoholics
 Biotin
 Structures of:
23
 Biotin
 Biocytin
 Biotin + the ε-amino groups of lysine
residues
 Carboxy-biocytin
 Formed from bicarbonate in an
ATP-dependent rxn
 Carboxygroup is then transferred
to the substrate for carboxylation
 The active metabolic intermediates

 Widely distributed in many foods

 As biocytin (-amino-biotinyllysine)
 which is released on proteolysis
 Biotin (Cont’d)
 Biotin deficiency does not occur naturally because
the vitamin is widely distributed in food.
Also, supplied by intestinal flora
 However,
 the addition of raw egg white to the diet induces symptoms of
biotin deficiency.
 contains a glycoprotein, avidin, which tightly binds biotin and
prevents its absorption from the intestine
 Coenzyme of Carboxylase Enzymes:
Functions to transfer Co2 in a small number of carboxylation rxn’s:
 Acetyl-CoA,
 Pyruvate carboxylases
 propionyl-CoA
 methylcrotonyl-CoA
Lipogenesis, gluconeogenesis, & catabolism of the branched-chain
AAs
Biosynthesis of malonyl-CoA. (Enz, acetyl-CoA carboxylase.)
 Folic acid
 A conjugated molecule consisting of
 A pteridine ring structure linked to PABA that forms pteroic acid
 Folic acid itself is then generated through
 Conjugation of glutamic acid residues to pteroic acid
 Has a number of derivatives known collectively as Folates
 Active form of folic acid (pteroyl glutamate):
Tetrahydrofolate (THF also H4folate)
 Folic acid is obtained
 Primarily from yeasts & leafy vegetables as well as animal liver
 Animal cannot synthesize PABA nor attach Glu residues to
pteroic acid
Thus, requiring folate intake in the diet
 Folic acid
 When stored In the liver orcon’t
ingested:
 It exists in a polyglutamate form
 Intestinal mucosal cells remove some of
the Glu residues  Conjugase
 The removal of Glu residues makes folate
less negatively charged
 More capable of passing through  basal
luminal membrane of the intestine
 Main circulating form of folate is the
N5-THF
 Folic acid is reduced to THF Within
liver cells
 DHFR, an NADPH-requiring enzyme
 Folic Acid
Positions 7 & 8 carry
Hydrogens in
 Dihydrofolate
Positions 5-8 carry
(DHF)
Hydrogens in
Tetrahydrofolate (THF)

Tetrahydrofolic acid and the one-

carbon substituted folates.
 Folate Functions

• Single carbon metabolism

 Folate Functions
 Interconversion of serine and
glycine
 Ser + THF <--> gly + 5,10-
Methylene-THF
 Degradation of histidine
 his>>formiminoglutamate(FIGLU)
 FIGLU+THF -> glu + 5-forminino-
THF
 Purine and Pyrimidine
Synthesis
 dUMP + 5,10-Methlene-THF ->
dTMP + THF
 Methionine Synthesis
 homocysteine + 5-Methyl-THF ->
MET + THF
 Folate Deficiency
• caused by poor absorption
– pathology of the small intestine
– alcoholism
– dihydrofolate reductase inhibitors (methotrexate) .
 A primary result of folic acid deficiency is
megaloblastic anemia caused by
 diminished synthesis of purines and
TMP
o leads to an inability of bone marrow
cells to synthesis DNA and
therefore,
 they cannot divide.
 results in large immature RBC’s
 Also it required for development of the
fetus' spinal cord and brain.
• There fore ,folic acid supplements at the
time of conception and in the first 12
weeks of pregnancy
 reduce the incidence of neural tube defects.
 Neural Tube Defects
Neural tube closes first 28 days of pregnancy
Forms brain and spinal cord
By the time pregnancy is confirmed, damage is done
 Vitamin B12 .
 Structure and Forms:
 Structure of Cobalamin is complex:
 It contains a corrin ring  w/c is similar to the porphyrin
ring
 Corrin ring differs from heme:
two of the four pyrrole rings are joined directly rather
than by a methylene bridge
the presence of Co3+ coordinated with the corrin ring
 Cobalt can form a bond with
 C of a methyl group  forming methylcobalamin or
 5-Cof 5-deoxyadenosine  5-deoxyadenosylcobalamin
 The form of B12 found in vitamin supplements is
Cyanocobalamin.
X=5’-deoxyadenosine in
5’-
deoxyadenosylcobalamin
X=CH3 in
Methylcobalamin
X= CN in Cyanocobalamin
Vitamin B12.
 Vitamin B12 (Cont’d)
 Absorption and Transport of Vitamin B12
vitamin B12 is produced by bacteria
it cannot be synthesized by higher plants or animals
It is absent from all plants but is concentrated in the
Livers of animals in 3 forms:
Methylcobalamin
Adenosylcobalamin &
 Hydroxycobalamin
Major source of vitamin B12 is foods of animal origin:
Dietary meat, eggs, dairy products, fish, poultry, & seafood
The animals that serve as the source of these foods obtain B12
 Vitamin B12 (Cont’d)
 The absorption of B12 from the diet is a complex process
Vitamin B12 Requires Transport proteins:
Intrinsic factor (IF)- parietal cell
Other cobalamin-binding proteins- R-proteins:
Secreted by the salivary glands and stomach
Along with trans-cobalamin (TC)I and III are now termed
Cobalaphilins
The third type of cobalamic protein  TCII
Ingested B12 can exist in two forms  either free or bound to
dietary proteins
If free, the B12 binds to proteins known as R-binders
(cobalaphilins)
in either the saliva or the stomach
 Vitamin B12 (Cont’d)
In the small intestine
 the pancreatic proteases digest the cobalaphilins,
the released B12 then binds to IF
The IF– B12 attaches to specific receptors in the
ileum
after which the complex is internalized
The B12 within the enterocyte complexes with TCII
then is released into circulation
The TCII–B12 complex delivers B12 to the tissues
The liver takes up approximately 50% of the
vitamin B12
the remainder is transported to other tissues
Fig-10. Absorption, transport, and storage of Vitamin B 12.
 Vitamin B12 (Cont’d)
 Functions of Vitamin B12
41
1. Transfer of a methyl group
From N5-methyl FH4 to homocysteine to form
methionine
FH4 receives a one-carbon group from Ser or
from other sources
This carbon is reduced to the methyl level
Transferred to vitamin B12:
Forming methyl-cobalamin
Methyl-cobalamin transfers the methyl
group to homocysteine
w/c is converted to Met by the enzyme
methionine synthase
 Vitamin B12 (Cont’d)
2. Rearrangement of the methyl group of
 L-methylmalonyl CoA to form succinyl
CoA
 the active form of the coenzyme is
5-deoxyadenosylcobalamin
 This rxn is part of the metabolic route
for the conversion of carbons from:
 Valine,isoleucine, tthymine
 the last three carbons of odd-
chain FAs
 all of which form propionyl CoA, to
the TCA cycle intermediate succinyl
CoA.
 Methylmalonyl CoA mutase
 Vitamin B12 (Cont’d)
 Vitamin B12 Deficiency Causes  Pernicious Anemia

The most common cause is:

failure of the absorption of vitamin B12
result of failure of IF secretion caused
By autoimmune disease affecting parietal cells or
From production of anti-intrinsic factor antibodies
IF lack can also be caused by gastric surgery
 Vitamin B12 (Cont’d)
 Vitamin B12 Deficiency Causes:

 Functional Folate Deficiency  the "Folate Trap"

 As the reduction of methylene-THF to methyl-THF is irreversible
 the major source of THF for tissues is methyl-THF
 The role of methionine synthase is vital
 Provides a link between the functions of folate and vitamin
B12
 Impairment of methionine synthase in vitamin B12 deficiency results in
 the accumulation of methyl-THF  the "folate trap"
Functional deficiency of folate, secondary to the deficiency of
vitamin B12
 TH4,VitaminB12,& S-
Adenosylmethionine
 Groups containing a single carbon atom can be transferred from
one compound to another
These carbon atoms may be in a number of different
oxidation states
The most oxidized form, CO2, is transferred by biotin

One-carbon groups at lower levels of oxidation than CO2 are

transferred by reactions involving
FH4
vitamin B12, and
 SAM
Relationship between FH4, B12,
and SAM

A. Overall scheme B. Some specific rxn’s requiring SA

 Ascorbic Acid (Vitamin C)

 Ascorbic Acid Is a Vitamin for Only Some Species

 Essential nutrient for
Humans and the higher primates the guinea pig, and
fruit-eating bats
 Other animals synthesize it as an intermediate in
Uronic acid pathway of glucose metabolism
 In those species for which it is a vitamin, there is a block in the
pathway
as a result of absence of gulonolactone oxidase
 Both ascorbic acid and dehydroascorbic acid have vitamin
activity
Ascorbic Acid Cont.
 Ascorbic Acid Cont.
Vitamin C is labile: Easily destroyed by
Oxygen
 metal ions
 increased pH
heat and
light
Vitamin C is a reducing agent:
Active form is Ascorbic acid 
Dehydroascorbic acid (oxidized derivative)
 Ascorbic Acid (Cont’d)
 Functions Vitamin C
Participates in Synthesis of
 collagen
 Carnitine
Neurotransmitters
Steroidogenesis
Bile acid formation
Degradation of tyrosine
Absorption of non-haem
Iron
Bonemineral metabolism
 Ascorbic Acid (Cont’d)
 Vitamin C as an Antioxidant
An important water-soluble antioxidant in biological fluids
Efficient scavenger of aqueous radicals and oxidants
Protecting other biomolecules from oxidative damage
Coantioxidant by regenerating Glutathione & Vitamin E
It may play a role in the prevention Atherosclerosis &
Cancer ?????
 There may be benefits from higher intakes of Vitamin C
At intakes above about 100 mg/day,
the body's capacity to metabolize is saturated
any further intake is excreted in the urine
There is little good evidence that high doses of vitamin C
prevent the common cold
 may reduce the duration & severity of symptoms
 Fat-Soluble Vitamins
 Fat-soluble vitamins  ADKE
55
 All of which are isoprenoid compounds
Synthesized by the condensation of multiple
isoprene units
 Not as readily absorbed or extracted from the diet
But ample reserves are stored in tissues
 Hydrophobic compounds that can be absorbed efficiently
only when there is normal fat absorption
 Transported in the blood in
lipoproteins or attached to specific binding proteins
 With the exception of vitamin K they do not act as coenzymes
 Vitamins A and D behave more like hormones (Serve as hormone
precursors)
 Vitamin A and vitamin D can be toxic in excess amounts
March 12, 2
025  This is not true of either vitamin E or K
 Vitamin A
 Two groups of compounds have vitamin A activity
Retinoids
56
Retinol, Retinaldehyde (Retinal ), & Retinoic acid 
Preformed vitamin A
Found only in foods of animal origin
Carotenoids
Found in plants
Carotenes and related compounds  Precursors of
vitamin A
The most important provitamin A carotenoids
quantitatively are
 -, -, and -Carotenes & Cryptoxanthin
β-carotene is converted to all-trans retinal
By the action of β-carotene dioxygenase in the small
bowel
 Vitamin A
Further metabolism in the enterocytes produces retinol
& retinoic acid
 w/c are then transported to the liver Stored as retinol
palmitate
 The stores of vitamin A in the liver comprise ≈ 1 year's
supply
Liver, egg yolk, butter, and milk - sources of Retinoids
Dark-green and yellow vegetables -sources of β-carotene
Structure, metabolism and function of vitamin A
 Vitamin A (Cont’d)
 Vitamin A from the liver needs to be transported to its sites
of action
It is transported by specific proteins:
 Serum retinal-binding protein (SRBP)
 Cytosolic retinal binding proteins (CRBP)
In addition, retinoic acid is thought to be transported to
cells
 Either bound to albumin or to a specific retinoic acid
binding protein (RABP)
Other tissue proteins are also involved
 In the molecular trafficking of retinol to the nucleus of
the cell
 Vitamin A (Cont’d)
 Retinoic acid has a role (as Hr.) Acting through receptor
proteins in the cell nucleus
Regulates gene expression in the development of epithelial
tissue, including skin
Retinoic acid is the active ingredient in the drug tretinoin
(Retin-A):
Used in the treatment of severe acne and wrinkled skin
61 Fig-vE: Summary of Actions of Retinoids. March 12, 2
 Action of
Retinoids
 Wald’s visual cycle
Vitamin A has a function in vision
In the retina, retinaldehyde functions as
the prosthetic group of the light-sensitive opsin
proteins
forming rhodopsin (in rods) and iodopsin (in
cones)
Any one cone cell contains only one type of opsin
is sensitive to only one colorIn the pigment epithelium of the
retina:
all-trans-retinol is isomerized to 11-cis-retinol
oxidized to 11-cis-retinaldehyde
This reacts with a lysine residue in opsin, forming the
holoprotein rhodopsin
 Wald’s visual cycle
The absorption of light by rhodopsin causes
Isomerization of the retinaldehyde from 11-cis to all-
64
trans,
Conformational change in opsin  Results in the:
Release of retinaldehyde from the protein
Initiation of a nerve impulse
The formation of the initial excited form of rhodopsin
bathorhodopsin, occurs within picoseconds of
illumination
There is then a series of conformational changes leading to
The formation of metarhodopsin II:
which initiates a guanine nucleotide
amplification cascade then a nerve impulse
The key to initiation of the visual cycle is
the availability of 11-cis-retinaldehyde
65 Fig-Ve: Retinoid metabolism in vision. March 12, 20
25 protein;
CRALBP, cellular retinal-binding protein; CRBP, cellular retinol-binding
IRBP, interstitial retinoid-binding protein; LRAT, lecithin:retinol
acyltransferase; RBP, retinol-binding protein; REH retinyl ester hydrolase
67 March 12, 2025
 Vitamin A (Cont’d)
In deficiency, both
the time taken to adapt to darkness &
the ability to see in poor light are impaired  ‘Night
blindness‘
Vitamin A also affects growth & differentiation of epithelial
cells; thus its deficiency
produces defective epithelialization and
keratomalacia - corneal softening and opacity
Severe vitamin A deficiency leads to  Xerophthalmia
Progressive keratinization of the cornea & to
permanent blindness
 Vitamin A (Cont’d)

 Is vitamin A protective against Cancer & CVD?

Recently β-carotene has received attention in
its role as an antioxidant.
Since normal epithelial cell growth and
differentiation depends on retinoids,
many human tumors (carcinomas) arise
from epithelial cells,
it has been proposed that it may be
protective against these diseases
 Vitamin D
Vitamin D
 is a group of sterols having similar
physiologic activity
 2 sources

 90% synthesised in skin via UVB light

exposure
 Cholecalciferol (vitD3 = inactive)

 10% from food

 Ergocalciferol (vit D2= inactive)

Forms
 D2-calciferol is activated ergosterol
(plant origin).
 D3 is activated 7-dehydrochelesterol in
skin (animal origin)
 Then cholecalciferol transferred to the
liver.
 Vitamin D
In the liver
 Vitamins D and D are not
2 3
biologically active
 They are activated to 25-OH-
cholecalciferol by
 liver specific 25-
hydroxycholecalciferol
hydroxylase
subsequently, in the renal cortex to
1,25dihydroxycholecalciferol
 which functions as a hormone
 By 25-hydroxycholecalciferol 1-
hydroxylase
Receptors for 1,25-diOH D3 are present in
most tissues, but its roles are facilitation
of :
 Intestinal absorption of Ca &
PO4.
 Renal reabsorption of PO4.
 A direct effect on bone deposition
& reabsorption of Ca & PO4.
 with parathormone & calcitonin,
1,25-diOH D3 plays a major role
in Ca &PO4 homeostasis of both
body fluids & body tissues.
 Vitamin D
 The overall function of 1,25-diOH-
D3
 To maintain adequate plasma
levels of calcium by
1. increasing uptake of
calcium by the
intestine
2. minimizing loss of
calcium by the kidney,
and
3. stimulating
resorption of bone
when necessary
 Vitamin D
How 1,25-diOH-D3
enhances
absorption?
 1,25-diOH-D3 enters
the intestinal cell and
binds to a cytosolic
receptor.
 The 1,25-diOH-D3–
receptor complex
then moves to the
nucleus where it
selectively interacts
with the cellular DNA. Figure 28.23 Metabolism and actions of
 Then ,calcium uptake vitamin D. [Note: Calcitonin, a thyroid
hormone, decreases blood calcium by
is enhanced by an inhibiting mobilization from bone and
increased synthesis reabsorption by the kidney.]
Clinical indications
1. Nutritional rickets:
 causes a net demineralization of bone
 resulting in rickets in children and osteomalacia
in adults.
Rickets is characterized by
 the continued formation of the collagen matrix of
bone
 but incomplete mineralization, resulting in soft,
pliable bones.
2.Renal rickets (renal osteodystrophy)
 This disorder results from chronic renal failure
and
 thus, the decreased ability to form 1,25-diOH -
D3
 administration is effective replacement therapy.
3.Hypoparathyroidism:
 Lack of parathyroid hormone causes
hypocalcemia and hyperphosphatemia.
 These patients may be treated with any form of
 Vitamin E
 Vitamin E is the generic descriptor for two families of compounds
 Tocopherols & Tocotrienols
75 90% of vitamin E present in human tissues is
 In the form of the natural isomer, α-tocopherol
Tocopherols have
 a substituted chromanone nucleus
 with a polyisoprenoid side chain of variable
length;usually 3 isoprene units
The richest sources of naturally occurring vitamin E are
 Vegetable oils & Eggs  Especially abundant in wheat
germ
In European folklore, vitamin E has been associated with
 fertility & sexual activity
This is certainly true in other animal species where vitamin E
plays a role in
 sperm production and egg implantation, but this is not
the case in man
 76

The vitamin E vitamers.

 In α-tocopherol and tocotrienol
R1, R2, and R3 are all -CH3
groups.
 In the β-vitamers R2 is H;
 in the γ-vitamers R1 is H, and
 in the δ-vitamers R1 and R2 are
both H.
Structure of vitamin E family (tocopherols)
R1-R3 can be methylated in a variety of combinations. The polyisoprenoid side chain occurs at R4.
Me, methyl
 FUNCTIONS
• The main function of vitamin E is anti
oxidant. It intercepts free radicals &
prevents destruction of cell
membrane.
• It protects the fat in LDL from
oxidation.
• It inhibits platelets aggregation.
• It enhances vasodilatation.
• It inhibits the activity of protein
kinase C.
 Vitamin E (Cont’d)
 It is the most abundant natural antioxidant
Owing to its lipid solubility, it is associated with
all lipid-containing structures:
membranes, lipoproteins and fat
deposits
It is absorbed from the diet with other lipid
components  no specific transport protein
In the circulation it is associated with
lipoproteins
Deficiency of vitamin E in premature infants causes
 Vitamin E (Cont’d)
 Vitamin E is the major lipid-soluble antioxidant
79  In cell membranes & plasma lipoproteins
As a chain-breaking, free-radical trapping antioxidant

 by reacting with the lipid peroxide radicals formed

by peroxidation of PUFAs
The tocopheroxyl radical (TocO•)) product is relatively
unreactive:
 Ultimately forms non radical compounds
 TocO• is reduced back to tocopherol (TocOH) by rxn
with vitamin C
The stability of the tocopheroxyl free radical means that
 80

Interaction and synergism between antioxidant systems operating in the

lipid phase (membranes) of the cell and the aqueous phase (cytosol).
 Vitamin K
 Independently discovered that
Vit. K deficiency slows blood clotting,
which can be fatal
 3 Cpds have the biological activity of Vit. K:
 Phylloquinone  Found in green vegetables,
normal dietary source
 Menaquinones Synthesized by intestinal
bacteria, with differing lengths
of side chain
 Menadione and menadiol diacetate,  synthetic
compounds that can be metabolized to
Menaquinones
 Its dietary sources are
green leafy vegetables also fruits, dairy
products,
 82

The vitamin K vitamers.

Menadiol (or menadione) and menadiol diacetate are synthetic compounds
that are converted to menaquinone in the liver and have vitamin K activity.
 Vitamin K (Cont’d)
 Like vitamin E, the absorption of vitamin K
 depends on appropriate fat absorption
 Vitamin K circulates as phylloquinone
 its hepatic stores are in the form of
menaquinones
 Vitamin K is the coenzyme for carboxylation of
glutamate
 It is required for the post-translational modification of
several proteins
 Factors II, VII, IX, X, and Prothrombin
 All of these proteins are synthesized by the liver as
inactive precursors
 Activated by the carboxylation of specific Glu
residues  Vit. K-dep. enzyme
 Prothrombin contains 10 of these carboxylated
residues (Gla)
 all are required for this protein's specific chelation
 Vitamin K (Cont’d)
 In the post synthetic modification of proteins to form
 Unusual amino acid -carboxyglutamate (Gla)
Chelates the calcium ion
 Initially, vitamin K hydroquinone is oxidized to the epoxide

 Activates a Glu residue in the protein substrate

to a carbanion

 Then reacts nonenzymically with CO2 to form

Gla
 Vitamin K epoxide is reduced to the quinone by
 warfarin-sensitive reductase
 Quinone is reduced to the active hydroquinone by
either
 warfarin-sensitive reductase or
 85

The role of vitamin K in the biosynthesis of γ-

carboxyglutamate.
 Fig-vK: Vitamin K–dependent formation of
86
-carboxyglutamate residues. March 12, 2
 Vitamin K (Cont’d)
 Vitamin K is required in the hepatic
synthesis of prothrombin and blood
clotting factors II, VII, IX, and X.
 These proteins are synthesized as
 inactive precursor molecules.
 Formation of the clotting factors
requires the vitamin K–dependent
carboxylation of glutamic acid
residues .
 This forms a mature clotting factor
that contains Gla and is capable of
subsequent activation.
 The reaction requires O2, CO2, and the
hydroquinone form of vitamin K.
 The formation of Gla is sensitive to
inhibition
 by dicumarol, an anticoagulant
occurring naturally in spoiled sweet
clover, and
 by warfarin, a synthetic analog of
vitamin K.
 Vitamin K (Cont’d)

 The Gla residues of prothrombin are good chelators of positively charged

calcium ions,
 because of the two adjacent, negatively charged carboxylate groups
 The prothrombin–calcium complex then able to bind to phospholipids
 essential for blood clotting on the surface of platelets
 Attachment to the platelet
 increases the rate at which the proteolytic conversion of prothrombin to thrombin can
occur