AfraTafreeh.

com

Unit 2.2
Clinical features related to vitamin A
 Effects of deficiency of vitamin A :
 Night blindness : vitamin A behaves as a prosthetic in case of
holoprotein rhodopsin and if vitamin A is deficient efficienc y of
holoprotein decrea ses and breaking of aldimine linkage wont
happen and as a result hyperpolarization is not observed ,
which causes night blindness.
 Xerophthalmia : dry eye , have many reasons with one being
vitamin A deficiency. Vitamin A deficiency can cause dryness of
conjunctiva and cornea.
 Bitot’s spot s : can be on medial or mostly on lateral side

1
  Follicular hyperkeratosis : appearance is like toad skin ,
phrynoderma. It is because of problem in turn over issues as
the dead skin is not getting shed off and is getting along with
the new skin.

AfraTafreeh.com

 Epithelial metaplasia: transformation of one epithelial type to

another is observed .it may further lead to neoplasia which is
very dangerous.
 Impaired embryogenesis: may cause teratogenesis i.e. process
by which congenital malformations are produced in embryo or
fetus. May cause retarded growth in children.
 Immune dysregulation: resulting in succumbing infections.
 Reasons for deficiency of vitamin A

2
 AfraTafreeh.com

 Liver di sorder or any obstruction in biliary tract will affect bile

secretion which in turn causes malabsorption of fats including
vitamin A.
 Some infections may cause deficiency as measles. A child who
survives measl es is chronically malnou rished.
 Alcohol is one of the reasons of malabsorption of vitamins.
 Even protein malabsorption may result in vitamin deficiency as
no transporters will be present and also no enzymes for
breakdown
 More vitamin A is also harmful as it may result in :
 Pseudotumorcerebri : it is a situation with increased pressure
in intra cranial area. Which also causes papilledema i.e. swelling
in optic nerve causing visual disturbances headaches etc.
 Liver damage : as lysosomes wont be able to clear that much
vitamin A .
 Teratogenesis
 Pathological fractures that means breakdown of bone because
of some disease and not because of any injury.
 Bony exostosis and pain in bones( vitamin A and vitamin D are
interconnected.
 Most common deficiency observed is vitamin A which can most
commonly cause preventable blindness.
 Zn deficiency has to play an important role in concrete vitamin A
deficiency as it inhibits mobilization of vitamin A from liver stores to
peripheral tissue and causes retinol deficiency which causes
decreased vitamin A
 Vitamin A is therapeutically used to treat cutaneous porphyra ,
beta carotene is very important because of its antioxidant nature.
If light falls on skin photo-isomerization of porphyra is observed
which activates macrophages ,mast cells and release of histamine .

3
 macrophages attack the skin and make it more dark and fragile,
which sometimes may cause bleeding.
 Because of its turnover function it is acne resistant.
 All trans retinoic acid may cause promyelocytic(anemia) leukemia.

AfraTafreeh.com

4
 AfraTafreeh.com

Unit 2.3

Fat soluble vitamin D

 Also called as antirachitic vitamin as it fights against

rickets.
 Pre vitamin D is converted into active form in presence of
sunlight and that’s why it is also called as sunshine
vitamin.
 If we talk about forms of vitamin D , we have pre vitamin D
:
 Ergo(g) calciferol : vitamin D 2
 Cholecalciferol : vitamin D 3
 Above mentioned forms are generally obtained through
diet but one of the main sources of vitamin D is skin,
specifically Malpighian layer of epidermis and in form of 7-
dehydrocholestrol .
 If we walk under the sun UV rays (290 -320 wave length)
the compound 7-dehydrocholestrol gets converted into
another pre vitamin form called cholecalciferol. Now in
winters because of UV light not being of appropriate
frequency at solar zenith angle (above then 320 as the
solar radiation absorbed or reflected is mediated by zenith
angle) 7-dehydrocholestrol cannot be converted into
cholecalciferol which results in seas onal deficiency of
vitamin D.

1
 Now it’s clear that cholecalciferol will be less in areas with
less sunlight as Polar Regions.
 As we discussed that pre vitamin D 3 can be converted into
cholecalciferol
In presence of sunlight but excess of sunlight is also bad
as it can destroy the vitamin.
 Now as in skin cholecalciferol is formed in skin , it
undergoes hydroxylation reaction ( addition of OH) in liver
at 25 t h position forming 25 -hydroxy cholecalciferol which
in kidney is converted into 1,25 -dihydroxy cholecalciferol
(calcitriol) having 3 OH groups in presence of 1 -alpha
hydroxylase enzyme.
 Calcitriol is the active form of vitamin D
AfraTafreeh.com
 Prominent and major storage form of vitamin D is 1,25 -
dihydroxy cholecalciferol.

2
 AfraTafreeh.com

( synthesis of vitamin D in the skin )

 As we saw kidney is responsible for ultimate step of

vitamin D synthesis and is also responsible for
erythropoietin synthesis , so in case of chronic kidney
disease both the function will be restricted , which will
cause anemia ( blocking od erythro poietin pathway ) and
osteoporosis ( deficiency of active vitamin D)

(metabolism of vitamin D)

 The process of conversion from pre vitamin forms to

active form is like :

Calciol

3
 Calcidiol

Calcitriol

Calcitetriol

AfraTafreeh.com


 ( synthesis and activation of vitamin D)

4
 AfraTafreeh.com

 Diet must include vitamin D in case the person is not

exposed to sunlight in optimum range.
 Vitamin D 3 is generally prepared from animal products and
then irradiated with UV rays as milk and cereals fortified
with vitamins.
 Vitamin D is in relation with amounts of calcium in blood
as :
 It is responsible for reabsorption of calcium in
kidney.
 It is responsible for resorption of calcium in bones.
 It plays important role in absorption of calcium in
intestine.
 All these three fa ctors are responsible to increase levels
of calcium in blood which is synergistic to action of
parathormone . parathormone works through vitamin D
whereas vitamin D can work independently.

Dig 14:47 (absorption of calcium )

 vitamin D 3 present in blood tra vels to intestinal cells and

combine to intracellular receptors forming complex which
in turn binds to DNA and activates transcription and
translation for protein called calbindin which binds with
calcium and helps in absorption.
 So if vitamin D decreases absorption of calcium decreases
, resorption of calcium decreases and reabsorption of
calcium also decreases.

5
 If we consider actions of vitamin D , being a steroid
hormone with intracellular receptors, its actions are not
lightning fast but takes time and are persistent.
 Anti-proliferative hormone : vitamin D , tries to keep
proliferation of cells under check which as a result
decreases chances of cancer specially in colon
,prostate,breast.
 Immune modulatory action vitamin D can also help in
increasing synthesis of cathelicidin which helps the
organism in making peptide called defensin which have
innate immunity protection along with ApoBEC -3G and
lysozymes which work against intracellular infection.
 Because of antiproliferative function of vitamin D it
AfraTafreeh.com
decreases any kind of autoimmune overflow to beta cells
of pancreas which is act ually main reason of diabetes
mellitus and X syndrome .
 Effects of deficiency of vitamin D :
1. Rickets (children) : bow shaped legs and rachitic
rosary as a result , which refers to expansion of the
anterior rib ends at the costa chondral junctions.
2. Osteomalacia i.e. softening of bones which in older
age may result into fractures.
 If we consider hyper -vitaminosis which is most toxis in
vitamin D :
1. Calcinosis cutis : soft tissue cal cification is observed

6
 AfraTafreeh.com

2. Increased amount of vitamin D will cause

hypercalcemia resulting in neo -plastic psammoma
(collection of calcium in round shape) body formation
3. Increased amount of PO 4 3 -
 Deficiency of vitamin D can happen due to :
1. Extra covering of skin ( wearing extra clothes always
like in case of burqa as a tradition in Islam
community )
2. Extra pigmentation of skin
3. Ageing
4. Hidden in room for long time
5. Fat malabsorption
6. Obstructive jaundice
 Some are important points regarding vitamin D :
 If amount of 25-dihydroxy cholecalciferol is less as a
reflex amount of calcitriol , PTH and ALP will
increase.
 In serum most abundantly present is 2 -dihydroxy
cholecalcipherol which is accessor parameter for
status of :
 Diet based intake of vitamin D , as more the
amount in serum more is the intake.
 How much our skin is exposed to sun as more
exposure more presence of 25 -dihydroxy
cholecalciferol in serum.

7
 If we consider quantity that should be present it
should be more then 15 n-mole per liter for 25 -
dihydroxycholecalciferol.
 In circulation recommended levels of vitamin D is
like :
Amount Status

<12.5

12.5<amount<30

30<amount<50

=50

AfraTafreeh.com
50<

>300nmoleperlitre

8
 AfraTafreeh.com

Unit 2.4 – Missing Video File

Fat soluble vitamin E

vitamers of vitamin K.

 Also mentioned as tocopherols , out of which 8 are naturally

occurring.
 Greatest amount of biological activity of vitamin E id performed by
5,7,8trimethyl-tocol. Structure is basically about chromane ring
systems which is core component of vitamin E.
 Just like vitamin A has beta ionone and vitamin D has steroid
nucleus, vitamin E has chromane including different tocol rings.
 Vitamin is also called anti sterility vitamin , even vitamin A is
responsible for fertility but its deficiency doesn’t cause sterility.
 Vitamin is a fat soluble intracellular antioxidant.
 Vitamin E is an antioxidant so prevent oxidation i.e. burning
combustion so it is anti-ageing.

1
 It is also antiatherogenic, as it inhibits fatty depositions. Generally
whenever HDL > LDL atheromatic block is formed which initiate free
radicle reaction, later on becoming a thrombus and getting
detached as embolus.
 Vitamin E is stored in liver. It is not readily formed inside body and
must be included in diet. Vitamin E is absorbed through chylomicrons.
 There is a strong connection between vitamin E,vitamin C and
selenium. Selenium and vitamin E have a sparing effect on each
other.
 Whenever concentration of selenium decreases vitamin E increases
and vice versa.
 Vitamin E is also anti-inflammatory, by having negative regulation on
prostaglandin synthesis ultimately mediating inflammation, fever and
pain.it does so by blocking activity of protein kinase A and
phospholipase A 2 AfraTafreeh.com
 Deficiency of vitamin E :
 Periphe ral neuropathy (axonal degeneration) , this deficiency
can mimic the pyridoxine deficiency that happens because of
intake of anti tubercul osis drugs inhibiting pyridoxal kinase.
 Because of this inhibition pyridoxal cannot be converted into
pyridoxal phosphate i.e. vitamin B 6 . So we can say that
deficiency symptoms for vitamin E and B6 run parallely.
 Stereognosis is affected.
 Vibrations are not felt.
 Retinal muscular atrophy retinopathy is caused by vitamin E
deficiency and vitamin A deficiency corresponds to macular
degeneration. Deficiency of Vitamin A and Vitamin E together
cause extreme harm to vision.
 Spinocerebellar ataxia

2
 AfraTafreeh.com

 If vitamin E levels are low then the ability of reducing oxidants

decreases causing increase in number of radicles who may
attack RBC membrane. RBC membrane is stable and safe in
reduced form but because of vitamin E being deficient RBC
looses its form and breaks causing hemolytic anemia.

(interaction between antioxidants in lipid phase in cell membrane or in

aqueous state of cytosol)

 Conditions which are benefitted because of vitami n E therapy:

 Retrolental fibroplasia, a new born baby is not able to breath
and we put him on hyperbaric oxygen-therapy , due to which
to accommodate more amount of oxygen new vessels are
formed and when the therapy is stopped vessels will shrink
and become fibrous tissue.
 Intermittent claudication

3
  Beurger’s disease also called as thrombo-angiitisoblitera ns as
blood vessels become inflamed, swell and can be blocked by
blood clots
 Intraventricu lar hemorrhage of prematurity attenuation.
 Easily delay ageing process
 Recommended diet ary allowance for vitamin E is 15-20 mg per day
 Vitamin E is present in vegetable oil like sunflower, safflower, wheat
germ oil and not from fish liver oi l unlike other vitamins
 Hypervitaminosis E is caused on intake more than 500mg per day
which leads to hemorrhagic tendency as vitamin E behave as an
anticoagulant (minimalistic action)

AfraTafreeh.com

4
 AfraTafreeh.com

Unit 2.5
Fat soluble vitamin K
 Earlier it was called as coagulation as excess and deficiency of
vitamin K is seen during coagulative diathesis
 Structure has isoprenoid side chains, which determines dif ferent
structures.
 If 20 C side chain is present it is vitamin K1, phylloquinone
 If 30 C chain then vitamin K2, menaquinone
 Menadione with water soluble actions is form of phylloquinone itself
and have a nullified side chain
 Chylomicrons are very important in fat absorption
 Vitamin K synthesis generally happens in intestine and then store d
in liver and for transportation beta-lipoproteins are used

1
 AfraTafreeh.com

 Phylloquinone is plant derived and has one side chain ,

menaquinone has n times repeated side chains and menadiol has
a nullified side chain with both keto groups reduce d into
menadioldiacetate in liver
 The only fat soluble vitamin that can act as coenzymes along
with an enzyme in a biochemical reaction is vitamin K
 In our body proteins have Gla domains for binding to calcium. As
we know calcium is a divalent cation and will need two negative to
get accepted so in proteins.

2
 AfraTafreeh.com

 Proteins who want to accept calcium must have a divalent anion

ans so their glutamic residues must be carboxylated into gla
domains and for this carboxylation vit amin K is important.
 If we observe the process there is an important step during
carboxylation and that is CO2 addition which needs vitamin K. it
will bw a part of couple reaction and along with it Vitamin K cycle
is working as :

(carboxylation and vitamin K cycle)

 Whenever we see sulfhydryl groups they will turn into di-sulfide
bond and in this way disulfide removes oxygen from vitamin K
epoxide. Now formation of vitamin K quinone is observed which is
complete oxidized form. And this form will again undergo
reduction in presence of NADPH and disulfi de (GSH dependent)

3
  Warfarin can block the enzymes involved in vitamin K cycle which
may result in cycle being stopped.
 Biological function of vitamin K is to form gla domains by gamma-
decarboxylation so that the protein can accept calcium.
 Now if we collectively see the effect of vitamin K on our body it
will be :
 Proteins involved in coagulation cascade i.e. 2,7,9,10factore ,
protein-S and protein-C must be activated to accept
calcium by their gamma decarboxylation which is done with
help of vitamin K
 Protein resp onsible for bone metabolism i.e. osteocalcin also
needs to form gla domains in order to accept calcium for
proper bone mineralization.
 Vascular smooth muscle matrix protein
 Nephrocalcin also follows same pathway and its deficiency
AfraTafreeh.com
mey result in deterioration of kidney functions.
 Reasons for deficiency of vitamin K:
 Fat malabsorption caused du e to intestinal injuries or
obstructive jaundice.
 Antibiotic abuse as this may kill the commensal bacteria which
provide us vitamin K
 New born children only feeds on breast milk which is a poor
source of vitamin K and not many commensal bacteria are
present, causing relative vitamin K deficiency which further
results in hemorrhagic diseases.
 Warfarin abuse: warfarin is drug used to block vitamin K epoxide
reductase so no reduction that means no vitamin K cycle so no gla
domains will be formed and therefore no coagulation.
 Fetal warfarin syndrome: bony defects will be observed specially
glass like appearance of pelvis. Because warfarin nullifies gla domain

4
 AfraTafreeh.com

formation in osteoc alcin which affects bone mineralization and

causes several abnormalities.
 Hypervitaminosis K:
Coagulation will be extreme causing hyper bilirubin i.e. prehepatic
jaundic e which increases amount of unconjugated bile which can pass
through blood brain barrier, enters into basal ganglia and cause
brain damage. Bone s will become brittle because of extra calcium
and also affects kidney functions.

5
Unit 2.6
Water soluble vitamin: thiamine (B1)
 Water solubl e vitamins involve B-complex and vitamin C.
 Vitamin B1 is the water-soluble vitamin also called thiamine.
 Thiamine is vitamin but thymine is pyrimidine that is nitrogenous
base.
 Active form of thiamine is thiamine diphosphateand it is also called
thiamine pyrophosphate. As when the bond is broken the energy is
released in form of heat.
 Substituted pyrimidine if combined with substituted thiazole bound
to pyrophosphate which makes it active form of vitamin B1
 Thiamine is not motile or active until pyrophosphate is attached to
it.
AfraTafreeh.com

 Carbanion form of thiamine will have electron sink property. This

structure is required for nucleophilicvs electrophilic attack.
 Thiazole rings are present in antibiotics which are referred as
beta-lactam antibiotic.

1
 AfraTafreeh.com

(structure of beta lactam)

 The electron sink property is responsible for inhibition of enzymes
transpeptidase. Transpeptidase is important for cross linkage of
peptidoglycan to form a meshwork and only when a meshwork is
formed it can be called a cell wall. Beta lactam antibiotics inhibit
transpeptidase which thus prevents cell wall formation making the
organism vulnerable.
 Every water solub le vitamin should act as a co enzyme for some
other enzyme and that enzymes will be involved an a reaction.

2
 Thiamine pyrophosphate can act as coenzyme for enzymes cleaving
C-C bond.
1. PDH complex which is complex enzyme used in liker reaction
between glycolysis and TCA cycle. In PDH complex there are 3
enzymes and 5 vitamins are present. One of vitamin is
thiamine.
2. Alpha-ketoglutarate dehydrogenase complex in carbohydrate
metabolism
3. Branched chain alpha-ketoglutarate dehydrogenases involved
in amino acid metabolism.
4. HMP shunt have trans-ketolase enzymes.
 The support to tryptophan pyrolase enzyme who can break indole in
tryptophan. Tryptophan pyrolose activity is supported by thiamine.
 The special compounds coming out of tryotophan may be attributed
to deficiency of vitamin B1.
 In case of branchedAfraTafreeh.com
chain alpha-ketoglutarate dehydrogenase
deficiency may lead Maple syrup test.
 If linker is lost during then the next option is lactic acidosis as
pyruvate is not able to move forward to become acetyl-co-A. So
TCA cycle is not possible, causing decrease in amount of ATP.
 HMP shunt blocking of trans-ketolase can affect then ribose
formation and NADPH formation be altered.
 Thiamine triphosphate is having direct involvement in chlorine
channel regulation. this is where it has direct involvement in chloride
channel regulation, we will be having conduction of nerve impulses
done properly
 So if at all thiamine is deficient part and may suffer neurological
deficits.
 Consistency to help trans-ketolase in RBCs, the RBCs have only one
source of energy in form of ATP. And they are not that well
prepared for oxidative stress, so NADPH is required while handling

3
 AfraTafreeh.com

the stress. But in case it all doesn’t get back to normal hemolysis
will happen causing hemolytic jaundice.
 RBC transketolase function can be tested in:
1. Absence of thiamine pyrophosphate in estimation system: activity
is lesser
2. Adding in estimation system: activity is more
 Vitamin B1 can be obtained from: cereals, unpolished rice, aleurone
layer on grains.
 Yeast can give a good source of thiamine
 Nuts are also rich in thiamine.
 Whole wheat flour and unpolished handful rice can be a good source
of vitamin B1.
 RDA for thiamine is 1-1.5 mg per day
 When a patient is alcoholic, absorption of nutrients decreases.
 Alcohol is pure calorie with zero nutrition value.
 If a person is chronic alcoholic and having low amount of nutritional
value is vulnerable to Wernicke Korsakoff syndrome.
 Wernicke stands for encephalopathy and Korsakoff is for psychosis.
 Neurotic people will have insight whereas psychotic people doesn’t
have insight. Neurotic person will rea lize about what he did wrong
but psychotic will never understand and will repeat the same
mistake again.
 In above syndrome the CNS is at attack:
1. Global confusion
2. Ophthalmoplegia
3. Ataxia
4. Memory loss
5. Polyneuritis
 In general thiamine deficiency causes Beri-Beri which can be of 3
types as:

4
 1. Dry Beri-Beri: it can involve PNS and CNS.
Chronic peripheral neuritis is type of dry Beri-Beri and may
botassociated with heart failure.
2. Wet Beri-Beri: there is CVS involvement. Peripheral
vasodilation followed by cardiac failure which is followed by
dyspnea and tachy-cardia. Leading to cardiomegaly which may
cause pulmonary edema.
3. Neo-natal Beri-Beri: also called as Sosh inBeri-Beri. It is
referred to as acute pernicious disease.
 More diuretic may also cause deficienc y.
 Person having const antly tea will also face problem with this, as tea
has antivitamin in it, which will alter the vitamin B1.
 Shellfish activity
 When a patient is having psychosis he will start up making/filling up
stories on his own
AfraTafreeh.com
Which is called confabulation. If it is for long term it may cause
amnesia where people can not survive
 Treatment is giving in high dose thiamine that can be given
intravenously or int ra-muscularly for 3-8 days and oral thiamine. An
alcoholic person mistbe given more than a usual person.
 Even if thiamine is given in excess it will be lost with urine as it is
water solub le.

5
 AfraTafreeh.com

Unit 2.7
Water soluble vitamin: riboflavin and niacin
 Riboflavin and niacin are called twin vitamins

(structure of riboflavin)
 Riboflavin is made up of dimethyl isoalloxazine ring.
 Riboflavin is either present in form of FMN and FAD.
 FMN is combined form of riboflavin, D-ribitol and phosphate.
 To FMN if we add one more phosphate and ribose and nitrogenous
base, it becomes FMN nucleotide which is FAD.
 The most important function of FMN or FAD is to act as carriers to
the concept of electron transport chain so we have FMN being a

1
 part of complex 1. It accepts the hydrogen and electrons and then
loose it to FeS.
 In case of complex 2 the electrons are given by FAD, and from here
electrons will be given to Q.
 So FMN is belonging to complex 1 and FAD belongs to complex 2.
 The most common sources of riboflavin are:
 Unpolished grain
 Milk, egg, meat, liver, yeast
 Fresh fruits and vegetables
 Riboflavin is heat and acid resistant.
 Deficiency of riboflavin will cause magenta color tongue because of
cheilosis that happens where the pigmentation of tongue is altered.
 Angular stromatitis: cracking at angles od lips
 Seborrheic dermatitis
 Scales of skin will b e AfraTafreeh.com
seen like dandruff
 FAD and FMN have been known to help glutathione reductase which is
dependent on selenium to keep RBC intact in order to prevent from
oxygen attack.
 FAD are co-enzymes in different react ion involved.
 FAD and FMN helps in different unique functions
 In the three complexes i.e. PDH complex, AKGDH complex and
branched AKGDH complex on of the vitamin involved is riboflavin and
niacin.

2
 AfraTafreeh.com

(vitamin B3 niacin)
 Vitamin B3 is generally found on form of nicotinic acid, and can act
as anti-dyslipidemia agent prevents against dyslipi demia.
 The COO- group of niacin may take uo NH3+ to become nicotinamide
.
 Nicotinamide along with nucleotid e it is called nicotinamide adenine
dinucleotide .
 Common sources for niacin are:
 Unpolished rice
 Milk, egg, meat, liver, yeast, fish
 Legumes
 Niacin can be present in form of NAD or NADP. NADP is used in
reductive pathway. NAD is used in combustion reactions inside
mitochondria. But glycolysis also have NAD even though it occurs in
cytosol.

3
 The NAD+ oxidoreductases are of class 1 enzymes like :
 Lactate dehydrogenase
 Glyceraldehyde-3-phosphatase
 Pyruvate dehydrogenase complex
 Alpha-ketoglutarate dehydrogenase
 Branched alpha-ketoglutarate dehydrogenase
 Glutamate dehydrogenase which I stype of oxidative
deamination where oxidation happens in a way glutamate is
getting converted into alpha-keto acid. in this process also
NAD becomes NADH+(H+).
 Niacin has natural anxiety reliving property that’s why people call it
God’s own valium.
 Some theories claim that the niacin is just a product of tryptophan
reactions which is controlled by vitamin -B6. So, vitamin B6 deficiency
may ultimately cause niacin deficiency.
AfraTafreeh.com
 So, we can say that vitamin B3 and B6 are connected by tryptophan
pathway.
 60mg of tryptophan gives 1 mg of niacin.
 If tryptophan is taken in optimum amount will cause
satisfaction/relaxation by releasing serotonin.
 Nicotinic acid in its purest form may be given to increase HDL
concentration (highly possible) and to decrease LDL (low possibi lity).
So it can be given in primary and secondary lipidemia
 Niacin deficiency may happen because of:
1. Alcoholism
2. Vitamin B6 deficiency
3. Quinolinate phosphor ribosyltransferase is rate limiting enzyme
in production of niacin.
4. Any drug that inhibits activity of enzyme quinolinate phosphor
ribosyltransferase

4
 AfraTafreeh.com

 There is no hypervitaminosis in case of B complex vitamins as

they are water soluble, they can be lost in urine.
 But for time being it may cause flushing that is cheeks becoming
pale because of intense vasoconstricti on.
 It may cause hyperuricemia
 It plays important role in glucose intolerance
 Niacin has destructive effect on beta cells of pancreas so insulin
release decreases causing diabetes mallitus. Also, niacin down
regulates insulin re ceptors that leads to insulin resi stance
 Nicotinic acid along with statin causes accentuating
rhabdomyolysis, so muscle destruction will happen which can be
cured by stopping nicotinic acid

5
Unit 2.8
Vitamin B6, pantothenic acid and biotin
 Vitamin B6 is also called pyridoxine.
 It has classical vitamers as pyridoxine, pyridoxal and pyridoxamine.
 It can behave as co-enzyme. Its most important function is in amino
acid metabolism
 Bi-Bi theory and ping pong mechanism for transamination. To knock
off the COOH group from amino acid we must ficthe amino group so
that it doesn’t follow. For this we use pyridoxal which combines with
amino group to form pyridoxamine. most of the decarboxylation
reactions are dependent on pyridoxal phosphate except the ones
based on dehydrogenase complexes. In same way if amino group is
supposed to be released the COOH must be kept on hold and this is
also done by vitaminAfraTafreeh.com
B6. So, it is helping in transamination.
The ping pong mechanism when alanine combines with alpha-KG and
forms glutamate and pyruvate in presence of ALT we need PLP. In
this case when amino group have to be removed from alanine PLP
will form a Schiff base with alanine so it can be broken down to give
the required results. Ping pong mechanism is governed by
transaminase enzyme with help of PLP.
 PLP also helps in carbohydrate metabolism in glycogen metabolism
where breakdown of glycogen requires glycogen phospholipase which
requires vitamin B6 as a cofactor.
 Vitamin B6 is also important in tryptophan metabolism as when it
enters nicotinic pathway of synthesis will require presence of vitamin
B6. Therefore people with B6 deficiency will have B3 deficiency
 It Is helpful in heme synthesis, during the condensation reaction
happening where glycine and succinyl co-A forms delta-ALA. Patient
may suffer anemia.

1
 AfraTafreeh.com

 Xanthurenic acid pathway related to aromatic amino acid

metabolism. If here vitamin B6 I deficient It will cause
xanthurenicacidemia. It can be detected by RBC transaminase
activity. We will load patient with tryptophan, if tryptophan is
loaded it should go through pathway and catabolism should be
smooth but B6 deficiency xanthine acid will accumulate and will be
present in urea.
 Sensory neuropathy will be caused by excess B6.
 INH the drug for tuberculosis taken for may cause B6 deficiency as
the drug inhibits enzyme pyridoxal kinase.
 B6 is important for sphingolipid synthesis.
 B6 is also involved in transsulfuration reaction in case of
homocysteine metabolism. Interference in this reaction will cause
accumulation of homocysteine leading to disturbances in collagen
maturation and suspensory ligament smay become weaker leading
to lens popping out of socket which is seen as sunset sign/sun-rise
seen.
 Vitamin B6 can be obtained from:
o Egg
o Yeast
o Cabbage
o Roots and tube rs
 In tyrosine metabolism who is source of melanin in case of B6
deficiency the person may show signs of vitiligo.
 Deficiency manifestations seen in vitamin B6 are:
o Seborrhea
o Glossitis
o Cheilosis
o Neuropathy
o Sideroblastic anemia because of heme synthesis being blocked

2
 o Myocardial infarction is also possible.
 Deficiency manifestation happen because of:
o Alcoholic
o INH administration will increase kynurenine levels which will
increase xanthurenic acid which can be tested by tryptophan
test.
 B6 can be therapeutically used because:
o it can help in clearance of oxalate stones by altering the pH
o Gyrate atrophy of retina where patient has deficiency of
gamma ornithine amino transferase supported by B6
 Pantothenic acid:
 Different vitamers are pantoic acid and beta-alanine and they come
together in amide linkage. As alanine will have amino grou p and
pantoic acid will have carboxylic part which forms amide linkage
which is precursor for co-A which acts as a tail for acyl groups.
AfraTafreeh.com
 To make co-A from pantothenic acid, 4 ATPs are used.
 Beta-mercaptoethanol amine will have sulfhydryl groups which is
helpful in making disulfide linkages.
 Acetyl co-A on combining with choline will form acetyl choline which is
parasympathetic neurotransmitter.
 HMG co-A can take up two pathways either cholesterol synthesis or
aceto-acetone beta hydroxybutyrate with help of enzyme HMG co-A
synthase.
 If pantothenic acid is deficient it can causeGopalan’s burning foot
syndrome which shows melalgia.

3
 AfraTafreeh.com

 Co-A have a nucleotide in it.

(pantothenic acid and coenzymes A)

 Biotin: it is also referred as B7.

4
 (biotin, biocytin, and carboxybiocytin)
AfraTafreeh.com
 Biotin has a structure that looks like a lid has kept over pan. The
cap is the guanidine group which is component of arginine.
 Biotin has red uced urea in its structure.
 Biotin contains ring with aliphatic chain.
 Biocytin is active form of biotin and can be converted into carboxy-
biocytin by carboxylation and this requires a ATP molecule.
 Carboxy-biocytin can provide the carboxy group to any other
compound and make it carboxy-x.
 Biotin is involved in different reactions and helps following enzymes:
 Acetyl co-A carboxylase
 Beta-Methyl crotonyl co-A mutase
 Propionyl co-A carboxylase
 Pyruvate carboxylase
 There is a concept egg white injury. Avidin is in white of egg and
biotin is in yell ow, people consume raw eggs and in that case avidin

5
 AfraTafreeh.com

having avidity for biotin binds with it to form complex .this complex
is useless and wont help in any carboxylation reaction causing biotin
deficiency. In ELISA whether competitive or sandwich we look for
biotinylatedanalyte. The antigen antibody have strong bonding just
like avidin and biotin. This way we can do analyze the complexes in a
similar way.
 Affinity and avidity are different as in affinity the compounds
search for each other and avidity helps in making a strong bond.
Basically, affinity brings the compounds together and avidity keeps
them together.
 Biotin is important for our hair, nails and skin. High biotin dose can be
used for treating alopecia and abnormal nails.
 In biotin deficiency can lead to flaky skin and nails.
 Biotin deficiency causes Leiner’s disease
 There are biotin independent carboxylation reactions:
o Any reaction which is vitamin k dependent like in coagulation
cascade, glu to gla domain reactions
o Carbomoyl phosphate synthetase has no dependency on biotin.
o Malic enzyme involves pyruvate becoming malic acid by
introduction of C
o In purine rings the C6 addition from CO2 is also not
dependent on biotin.