13 .Vitamins Docx.copy Docx

8/21/2019 13 .Vitamins Docx.copy Docx

1/59

VITAMINS

Classifcation o vitamins

VITAMIN A

1. What is the highest yielding source o Vit.A !on May "##$

". %escri&e the chemistry' dietary sources' daily re(uirement' &iochemical

role and defciency maniestations o Vitamin A. !on May "#11

). %iscuss Vit.A under the ollo*ing headings. !on May "#1#

a. Sources

&. !recursor

c. +unctions

d. %efciency

,. Name the at solu&le vitamins. %escri&e the sources' daily re(uirements'

unctions and defciency maniesta-tions o Vit.A

. What is the recommended dietary allo*ance or Vit.A. !on May "##/

+at solu&le vitamins0

are A,D,E,K. Alf the fat soluble vitamins are isoprenoid compounds, since they

are made up of one ormore of ve carbon units namely isoprene units The term

vitamers represents the chemically similar substances that possess qualitatively

similar vitamin activity. Some examples of vitamers are

i. !etinol, retinal and retinoic acid are vitamers of vitamin A.

ii. "yridoxine, pyridoxal and pyridoxamine are vitamers of vitamin #..

+orms o Vit.A0

$. All the compounds %ith vitamin A activity are referred to as retinoids. They are

poly isoprenoid compounds havin& a beta'ionone rin& system.

(. )itamin A is a term reserved to desi&nate any com' pound possessin& the

biolo&ical activity of retinol

road classifcation0

$. Animal sources

(*+


2/59

$. )it.A$ refers to all forms of animal sources of )it.A except one type available

in sh.

(. )it A( refers to a less potent form present in fresh %ater sh and in sh oils.

t has an extra double bond in the rin&.

(. "lant source$. The α, β, and γ carotenes and cryptoxanthin are quantitatively the most

important provitamin A carotenoids.

(. The pro'vitamin, beta'carotene is present in plant tissues. t is cleaved in

intestine to t%o molecules of retinal but this conversion is ine-cient.

Althou&h it %ould appear that one molecule of 'carotene should yield t%o of

retinol, this is not so in practice / & of 'carotene is equivalent to $ & of

preformed retinol.

+orms o Vit.A10

$. 2etinol is )it.A alcohol. t contains b'ionine rin& and t%o side chains called

isoprenoid units.(. 2etinal is )it A aldehyde, t is required for the visual cycle and enables

rhodopsin to mediate vision. !etinal is reduced to retinol by retinal reductase

and retinal can also be oxidi0ed to retinoic acid. !etinal exists in isomeric forms

due to double bond side chains. All' trans variety is called )it A$ is most

common and )i.T A( has extra double bond in the rin&. $$'cis ' retinal is the

biolo&ically important compound.

1. 2etinyl ester is the transport form from intestines to liver as part of

chylomicron.

*. 2etinol 3almitate is the stora&e form in liver.

2. Vit. A acid retinoic acid The physiolo&ically most important acid derivative,functions at the &ene level as a li&and for specic nuclear transcription factors

thus, re&ulate many &enes involved in fundamental biolo&ic activities of the cell.

t is not reversible to other forms.

A&sor3tion and trans3ort

$. Dietary retinyl esters are hydroly0ed by pancreatic or intestinal brush border

hydrolases in the intestines. !etinol is released. Similarly, #'carotene s

hydroly0ed by b'carotene $2'$23 di oxy&enase of intestinal cells to release (

moles of retinal, %hich is a&ain reduced to retinol. The intestinal activity of

carotene dioxy&enase is lo%, so that a relatively lar&e proportion of in&ested

'carotene may appear in the circulation unchan&ed.(. The absorption is alon& %ith other fats and requires bile salts. n biliary tract

obstruction and steatorrhoea, vitamin A absorption is reduced.

1. !etinol enters mucosal cells %here it is re esteried into retinylester and

incorporated into chylomicrons and transported via lymph. Then they are ta4en

up by liver and stored as retinol palmitate.

*. Trans3ort rom 4iver to Tissues

$. 5hen needed retinol is released from liver and transported by plasma

retinol bindin& protein. The retinol'!#" complex binds to specic

receptors on retina and other cells and release into cells.

(. The retinol'!#" complex binds to specic receptors on the retina, s4in,

&onads and other tissues. The !#" does not enter in the cell. nside the

(*6


3/59

cytoplasm of cells, vitamin A binds to cellular retinoic acid bindin& protein

78!#"9 and nally to D:A

$. n the cells a cellular retinol'bindin& protein carries it to D:A to exert its

function.

iochemical unctions0$. Vision0

a. 2ods and cones0 !etina has rods and cones rods are involved in dim li&ht

vision and cones in bri&ht li&ht and color vision.

&. Wald5s visual cycle0

i. !hodopsin is present in the photoreceptor cells of the retina.

!hodopsin consists of opsin a protein and $$'cis ' retinal

ii. 5hen li&ht falls on retina, $$'cis retinal isomeri0es to all'trans'retinal.

This leads to conformational chan&es in opsin and &enerate nerve

impulse.

iii. "art of the all'trans'retinal is immediately isomeri0ed to $$'cis retinaland combines a&ain %ith opsin to form rhodopsin. The cycle is

repeated. ;eneration of nerve impulse %hen li&ht falls on retina, a

visual cascade is tri&erred. "hoton is absorbed by rhodopsin and

metarhodopsin is produced %hich in turn activates transducin

involvin& ;T" 7&uanine triphosphate9 . The activated transducin

activates cyclic A!s form dimers %ith vitamin D'receptor also. This explains %hy

deciency of vitamin A impairs vitamin D function.

(*?


4/59

/. )it.A is essential for the inte&rity of epithelium retinyl phosphate is essential for

mucus formation to maintain moist surface. This is due to the fact that retinol and

retinoic acid are required to prevent 4eratin synthesis.

+. !etinyl phosphate is also necessary for synthesis of &lycoproteins essential for

&ro%th.

6. !etinol and retinoic acid are necessary for synthesis of transferrin.

?. )it.A promotes immune response.

$@. 8holesterol synthesis and ;luconeo&enesis indirectly require )it A

$$. !etinol is necessary for the reproductive system. !etinol acts li4e a steroid hormone

in controllin& the expression of certain &enes. This may account for the requirement

of vitamin A for normal reproduction.

$(. Anti'oxidant property

a. There is a correlation bet%een the occurrence of epithelial cancers and

vitamin A deciency. The anticancer activity has been attributed to the

natural antioxidant property of carotenoids. resh ve&etables containin&

carotenoids %ere sho%n to reduce the incidence of cancer.

b. #eta carotenes may be useful in preventin& heart attac4s.

$1. 8holesterol synthesis requires vitamin A.


5/59

c. 5omen +2@

d. "re&nancy $@@@

%efciency maniestations0

$. Causes o defciency0

a. Decreased inta4eb. Gac4 of bile

c. Gac4 of !#"

i. 8irrhosis

ii. Severe "rotein deciency and inadequate !#"

iii. Goss of !#" in nephrosis

(. 9cular changes0

a. :yctalopia or ni&ht blindness di-culty of vision in dar4 and prolon&ed

dar4 adaptation time.

b. >eropthalmia dry, %rin4led and scaly conHunctiva dry and cloudy cornea

%ithout lusture and moisturec. #itot3s spots increased thic4ness of conHunctiva in either side of cornea.

d. Keratomalacia softenin& of cornea leadin& to corneal ulceration,

perforation and loss of vision.

e. ndia *@I of blindness in children is preventable as they are caused by

malnutrition.

1. S6in and mucous mem&rane0

a. Dry' thic4 and scaly s4in called phrynoderma

b. All epithelial membranes becomes brittle and atrophic.

c. !enal calculi due to epithelial sheddin& in urinary tract formin& a nidus

for calculi.d. Dryin& and crac4lin& of s4in leads to s4in infections

*. The reproductive system is adversely a=ected in vitamin A deciency.

De&eneration of &erminal epithelium leads to sterility in males

Assessment o defciency0

$. "rolon&ed dar4 adaptation time

(. Serum !#" level

1. Serum )it.A level 7:ormal is (2 to 2@ & Fdl9

%ietary sources0

$. Animal sources mil4, butter, cream, cheese, e&& yol4, sh liver oil and liver.

(. )e&etable sources carrot, papaya, man&o, pump4ins, D;G) 7dar4 &reen leafyve&etables9

:y3ervitaminosis. A

$. Excessive inta4e can lead to toxicity since the vitamin is stored.

(. Anorexia, irritability, headache, peelin& of s4in, dro%siness and vomitin&.

1. ncreased intra cranial pressure 7pseudo tumor cerebri9

*. Enlar&ement of liver is also seen in children. Ji&her concentration of retinol

increases lysosomal en0ymes, leadin& to cellular death.

2. S%ellin& and pain in bones

/. n pre&nancy it can lead to con&enital defects in fetus.

:y3ercarotenemia0

t can result from persistent excessive consumption of foods rich in carotenoids.

(2$


6/59

The s4in becomes yello%, but no stainin& of sclera as in Haundice is observed.

VITAMIN % ;C:948CA4CI+8294<

1. Name the active orm o Vitamin %. :o* is it synthesi=ed in the &ody Add a note

on its unctions' re(uirements and defciency maniestations. A3ril 1$$>". Write an essay on Vitamin %' indicating its chemical nature' ormation' &iochemical

roles' 3hysiological unctions' defciency maniestations' sources and

re(uirements. A3ril 1$$

). :o* is Vit.% converted converted to its active orm !on May "#1#

,. What is the maniestation o vit.% defciency in the &ody !on May "##$

. %escri&e the ormation and unctions o calcitriol. !on May "#1,

>. What is the vitamin *hich could &e defcient in 3eo3le *ho are not e73osed to

sunlight 873lain the mechanism. !on A3r "###

+orms o Vit.%

$. )itamin D is a fat soluble vitamin. lt resembles sterols in structure and functionsli4e a hormone

(. )itamin D( 7or er&ocalciferol9 is from plants and vitamin D1 7or cholecalciferol9 is

from animal sources. Er&ocalciferol and cholecalciferol are referred to as

provitamins. Durin& the course of cholesterol biosynthesis, +'dehydrocholesterol

is formed as an intermediate. n exposure to sunli&ht, both +'

dehydrocholesterol is converted to cholecalciferol in the s4in by the action of

ultraviolet radiations. 8ommercially the vitamin is derived from the fun&us,

er&ot. The er&osterol %hen treated %ith ultraviolet li&ht, er&ocalciferol or vitamin

D( is produced.Vitamin % is called the ?sun-shine vitamin@. There is no

)it.D$.A&sor3tion' trans3ort and storage

)it D is absorbed in the small intestine by the help of bile. t enters throu&h

lymph into blood circulation and is carried by alpha ( &lobulin. Giver and other

tissues store )it.D.

Activation o Vitamin %0

4iver0

The cholecalciferol is rst transported to liver, %here hydroxylation at (2th

position occurs, to form (2'hydroxy cholecalciferol 7calcidiol9. The hepatic (2'

hydroxylase is a microsomal monooxy&enase. t requires cytochrome "'*2@ and

:AD"J. (2'J88 is the maHor stora&e form.

!lasma0 (2'J88 is bound to Lvitamin D bindin& proteinL 7)D#"9, an alpha'( &lobulin.

idney0 n 4idney, it is further hydroxylated at the $st position to form $,(2'dihydroxy

cholecalciferol. Since it contains three hydroxyl &roups at $, 1 and (2 positions, it is

also called 8alcitriol. t is the active form of vitamin.D

iochemical 8Bects o Vitamin %0 The sites of action are

a. ;T'intestinal villi cells

b. bone osteoblasts

c. 4idney distal tubular cells.

IT0

$. 8alcitriol promotes the absorption of calcium and 3hos3horus from the

intestine. 8alcitriol binds %ith a cytosolic receptor to form a calcitriol'

(2(


7/59

receptor complex. This complex then approaches the nucleus and interacts

%ith a specic D:A leadin& to the synthesis of a specic calcium bindin&

protein. 8alcium upta4e is enhanced by an increased by this protein called

8albindin.

(. Thus, the mechanism of action of $,(2' diJ'D1 is typical of steroidhormones.

8Bect o Vitamin % in one0

$. n the osteoblasts of bone, calcitriol stimulates calcium upta4e for deposition

as calcium phosphate

(. 8alcitriol stimulates osteoblasts %hich secrete al4aline phosphatase. Due to

this en0yme, the local concentration of phosphate is increased. The ionic

product of calcium and phosphorus increases, leadin& to minerali0ation.

Alon& %ith "TJ it mobili0e 8a and phosphates from the bone to maintain

their plasma level also.

8Bect o Vitamin % in 2enal Tu&ules08alcitriol increases the reabsorption of calcium and phosphorus by renal tubules,

therefore both minerals are conserved 7"TJ conserves only calcium9 bone.

Kidney converts (2, Jydroxy cholecalciferol to (*,(2 ' DJ88 an inactive form

instead of

$'(2' DJ88 %hen )it D is available in plenty so that its biolo&ical action is 4ept

optimum levels.

2egulation o Vit.%0

$. $,(2 DJ88 synthesis is re&ulated by plasma levels of 8alcium and phosphate

and calcitriol itself.

(. Go% "lasma level of calcium enhances the parathyroid hormone secretion %hichin turn activates $'hydroxylase. Go% plasma phosphate directly activates $

hydroxylase.

1. Jypercalcemia decreases calcitriol. Go% dietary calcium and hypocalcemia

increase the rate of production of $,(2'DJ88.

*. 5hen calcitriol concentration is adequate, (*'hydroxylase in 4idney acts leadin&

to the synthesis of a less important compound (*, (2'DJ88. n this %ay, to

maintain the homeostasis of calcium, synthesis of (*,(2'DJ88 is also important

Vit % is a hormone - Dustifcation0

$. )it.D1 is synthesi0ed in the s4in by C) rays of sunli&ht.

(. 8alcitrol is produced in 4idneys.1. 8alcitrol has tar&et or&ans li4e intestine, bone and 4idneys.

*. Gi4e a steroid it binds to a receptor in the cytosol and stimulates the synthesis of

calcium bindin& proteins.

2. Actinomycin D is able to inhibit the action of 8alcitrol su&&estin& that the action

of calcitrol is at D:A transcription.

/. Gi4e hormone 8alcitrol has a feed bac4 re&ulatory system for its synthesis.

+. t combines %ith other hormone li4e "TJ and 8alcitonin to re&ulate 8a x " levels

in plasma.

6. Gi4e a hormone it has half life of $@ hours.

Causes or Vitamin % %efciency

$. Deciency of vitamin D can occur in people %ho are not exposed to sunli&ht

(21


8/59

properly, e.&. inhabitants of northern latitudes, in %inter months, in people %ho

are bedridden for lon& periods, or those %ho cover the %hole body 7purdah9.

(. :utritional deciency of calcium or phosphate may also produce similar clinical

picture.

1.


9/59

calcitriol.

e. )itamin DNDependent !ic4ets End or&an refractoriness to $,(2'DJ88 %ill

also lead to ric4ets. Either a decrease in the number of cytosolic receptor

or a structurally abnormal receptor is noticed. The bone disease has been

found to respond to me&adoses of calcitriol 712 m&Fday9.

2. ther actionsa. !ecent research has proved that most tissues possess vitamin D receptor

and several tissues have the en0ymes to &enerate calcitriol. $,(2'DJ88

has been found to have a modulatory e=ect on immunohematopoietic

system. Therapeutic doses &iven to children %ith ric4ets have been found

to correct the anemia, hypocellularity of the bone marro% and increased

susceptibility to infection. t has also been found to reduce the ris4 of

cancer and coronary vascular disease. #enecial e=ects have been

observed in patients %ith ADS.

2e(uirement o Vitamin %

a. 8hildren $@ micro&ram 7*@@ C9Fdayb. Adults 2 micro&ram 7(@@ C9Fday

c. "re&nancy, lactation $@ micro&ramFday

d. Above the a&e of /@ /@@ C per day.

Sources o Vitamin %

$. Exposure to sunli&ht produces cholecalciferol.


10/59

2. :ormal plasma level is less than $ m&Fdl

/. #iochemical functions

$. it has anti oxidant property and prevents the non en0ymatic oxidation of

various cell components.

(. t maintains the inte&rity of cell membrane and cell structure.1. t prevents peroxidation of polyunsaturated fatty acids. Selinium and )it.E

act syner&istically to minimi0e lipid peroxidation.

*. t prevents haemolysis of !#8s by J((

2. t preserves &erminal epithelium of &onads and thus prevents sterility.

/. t enhances the action of ala synthase and increases synthesis of heme.

+. t stabili0es coen0yme A and is involved in electron transport chain.

6. t prevents the oxidation of vit.A and carotenes.

?. t helps stora&e of creatine in muscles.

$@. t is required for intestinal absorption of amino acids.

$$. t is requird for nucleic acid synthesis.$(. t protects live from dama&e by carbon tetra chloride.

$1. t plays a role in prevention of cataract.

$*. t prevents oxidation of GDG and thus protects heart. t reduces the ris4 of

atherosclerosis by reducin& oxidation of GDG

$2. )itamin E also boosts immune response. )itamin E can depress leu4ocyte

oxidative bactericidal activity.

+. !DA $@ m& for man and 6 m& for %omenFday

6. Sources :uts, seeds, and ve&etable oils are amon& the best sources of alpha'

tocopherol, and si&nicant amounts are available in &reen leafy ve&etables and

fortied cereals, soybean, canola, corn, and other ve&etable oils.?. Deciency symptoms

$. Sterility in animals but no si&nicant symptoms in humans.

(. ncreased fra&ility of !#8s, minor neurolo&ical symptoms may be observed in

human.

$@. Toxicity nil found ho%ever t%o clinical trials have found an increased ris4 of

hemorrha&ic stro4e in participants ta4in& alpha'tocopherol.

VITAMIN

1. What is the role o Vit. in maintaining &ody haemostasis !on May "##$

". What are the &iological unctions o Vit. !on May "#1"

). State the unction o Vit. E 8. !on May "##$

,. Name the Vit. de3endant coagulation actors. What is the role o Vit. on

their activities !on Nov "##/F May "##)

. Sym3toms o Vit. defciency are met *ith more due to liver dysunction

than due to lac6 o the vitamin. 873lain *hy this is so. !on a3r "##"

$. )itamin K is a fat'soluble vitamin. The LKL is derived from the ;erman %ord

L4oa&ulation. There are t%o naturally occurrin& forms of vitamin K.

a. "lants synthesi0e phylloquinone, %hich is also 4no%n as vitamin 1.

b. #acteria synthesi0e vitamin "' desi&nated as menaquinone.

c. ) is a synthetic form.

(2/


11/59

(. 8hemistry they are napthoquinone derivatives %ith isoprenoid side chain.

1. Absorption )it K provided by diet or bacterial synthesis is absorbed in association

%ith chylomicrons %ith the help of bile salts. t is transported %ith GDG and stored in

liver.

*. #iochemical functionsa. )itamin K is necessary for coa&ulation. t brin&s about posttranslational

modication clottin& factors (,+,? and $@ produced as 0ymo&en in liver.

b. Vit. acts as coen=yme or the car&o7ylation o glutamic acid &y

en=yme car&o7ylase. ;amma carboxy&lutamate is formed %hich is critical

to the calcium'bindin& function of these proteins. They are ne&atively

char&ed 78'9 and they combine %ith positively char&ed calcium ions

78a(O9 to form a complex. The complex 7e&. prothrombin ' 8a9 binds to the

phospholipids on the membrane surface of the platelets. This leads to the

increased conversion of prothrombin to thrombin.

a. The formation of y'carboxy&lutamate is inhibited by dicumarol, ananticoa&ulant and %arfarin, a synthetic analo&ue and they can inhibit

vitamin K action.

a. The mineral'bindin& capacity of osteocalcin in bone also requires vitamin K'

dependent &amma'carboxylation of &lutamic acid residues.

b. )it.K is also involved in ET8 and oxidative phosphorylation.

2. !DA adult +@'$*@ micro&ramFday

/. Sources 8abba&e, cauliPo%er, tomatoes, spinach, alfa'alfa, &reen ve&etables, e&&

yol4, meat, liver, cheese and mil4 products.

+. 8auses for Deciency of )itamin K

a. n normal adults dietary deciency seldom occurs since the intestinalbacterial synthesis is su-cient to meet the needs of the body. Jo%ever

deciency can occur in conditions of malabsorption of lipids. This can result

from obstructive Haundice, chronic pancreatitis, sprue, etc.

b. "rolon&ed antibiotic therapy and &astrointestinal infections %ith diarrhoea

%ill destroy the bacterial Pora and can also lead to vitamin K deciency.

6. Deciency symptoms

a. vert vitamin K deciency results in impaired blood clottin&, usually

demonstrated by laboratory tests that measure clottin& time.

b. Jemorrha&ic disease of the ne%born is due to vitamin K deciency. The

ne%borns, especially the premature infants have relative vitamin Kdeciency. This is due to lac4 of hepatic stores, limited oral inta4e 7breast

mil4 has very lo% levels, $2 m&Fliter9 and absence of intestinal bacterial

Pora. t is often advised that pre'term infants be &iven prophylactic doses of

vitamin K 7$ m&


12/59

system due to structural similarity %ith vitamin K. Jence they are %idely

used as anticoa&ulants for therapeutic purposes.

?. Daily !equirement of )itamin K

a. !ecommended daily allo%ance is 2@'$@@ m&Fday. This is usually available in

a normal diet.$@. Sources of )itamin K

a. ;reen leafy ve&etables are &ood dietary sources. Even if the diet does not

contain the vitamin, intestinal bacterial synthesis %ill meet the daily

requirements, as lon& as absorption is normal.

$$. Toxicity

a. There is no 4no%n toxicity associated %ith hi&h doses of the phylloquinone

7vitamin K$9 or menaquinone 7vitamin K(9 forms of vitamin K. The same is

not true for synthetic menadione 7vitamin K19 and its derivatives.

b.


13/59

abbreviated as :ADO. n the case of :AD"O, one more phosphoric acid is

attached to the ribose of the A


14/59

+. :ADJ produced is oxidi0ed in the electron transport chain to &enerate AT".

ne :ADJ molecule is oxidi0ed in the respiratory chain to &enerate 1

molecules of AT"

6. :AD"J is also important for many biosynthetic reactions as it donates

reducin& equivalents2%A The daily requirement of niacin for an adult is $2'(@ m& and for children, around

$@'$2 m&.


8auses of deciency

$. Tryptophan deciency in diet e&. Stable food containin& sor&hum and mai0e

%here tryptophan is not metabolically available to body.

Deciency symptoms

$. "yridoxal deciency leads to inability to convert tryptophan to niacin.

(. Jartnup disease %here con&enital defect of absorption of tryptophan from

intestine is present.1. 8arcinoid syndrome %here tumor tissue utili0es lar&e amount of tryptophan

for serotonin synthe sis.

Dietary sources rich sources are dried yeast, rice polishin&, liver, peanut, %hole

cereals, le&umes, meat and sh.

!DA normally (@ m&Fday additional 2 m& for pre&nancy and lactation.

Therapeutic uses

"harmacolo&ic doses of nicotinic acid, but not nicotinamide, have been 4no%n to

reduce serum cholesterol by reducin& acetyl 8oA pool. :iacin is commonly prescribed

%ith other lipid'lo%erin& medications.

%efcency sym3toms0$. :iacin deciency is mostly seen amon& people %hose staple diet is corn or

mai0e. :iacin present in mai0e is unavailable to the body as it is in bound

form. urther, tryptophan content is lo% in mai0e.

(. !ellagra

a. :iacin deciency leads to the disease called pella&ra characteri0ed by

1 Ds diarrhea, dermatitis and de mentia.

b. Dermatitis consists of bri&ht erythema in feet, an4les and face

pi&mentation around the nec4 is called 8asal3s nec4lace. The

dermatitis is precipitated by exposure to sunli&ht.

c. Symptoms related to the di&estive system include a bri&ht redton&ue, vomitin&, and diarrhea.

d. Dementia occurs in chronic cases and ataxia and spasticity could also

occur.

e. :eurolo&ic symptoms also include headache, apathy, fati&ue,

depression, disorientation, and memory loss. f untreated, pella&ra is

ultimately fatal.

Thera3eutic uses o niacin0

$. :iacin inhibits lipolysis in the adipose tissue and decreases the circulatory

free fatty acids.

(. Triacyl&lycerol synthesis in the decreased.

(/@


15/59

1. The serum levels of lo%'density lipoproteins 7GDG9, very lo%'density

lipoproteins 7)GDG9, triacyl&lycerol and cholesterol are lo%ered. Jence niacin

is used in the treatment of hyperlipoproteinemia type b 7elevation of GDG

and )GDG9.

To7icity0$. ;lyco&en and fat reserves of s4eletal and cardiac muscle are depleted.

(. There is a tendency for the increased levels of &lucose and uric acid in the

circulation.

ASC92IC ACI%

). Write the sources' re(uirements' defciency maniestations'

&iochemical actions o Vit.C !on a3r "###

,. Vit C 3lays a role in 3ost translational modifcation- Dusty. !on %ec

"##)

. 873lain the role o ascor&ic acid in 3ost translational modifcation.!on May "##/

Chemistry0

$. Ascorbic acid is a %ater soluble vitamin destroyed by heat, al4ali and on

stora&e. +@Iis lost %hile coo4'in& inactivated if coo4ed in copper vessel.

(. 8hemistry t is a hexose and closely resemble monosaccharide t has enolic

hydroxyl &roup it is acidic and a stron& reducin& a&ent G'ascorbic acid and

dehydroascorbic acid are active forms D'ascorbic acid is an inactive form.

1. "lants and animals can synthesis ascorbic acid from &lucose via uronic acid

path%ay.


16/59

*. t is essential for hydroxylation of tryptophan to 2'hydroxy tryptophan for the

formation of serotonin.

2. t helps in oxidation of parahydroxy phenyl pyruvate to homo&entisic acid.

/. t enhances iron absorption from the intestines by reducin& ferric form to

ferrous form.+. t helps in reconversion of met'hemo&lobin to hemo&lobin.

6. t helps maturation of !#8 by involvin& in folate reductase that converts folic

acid to tetra folic acid.

?. ts presence in adrenal cortex indicates that it is necessary for the synthesis

of steroids.

$@. t helps bile acid synthesis form cholesterol.

$$. "romotes pha&ocyic activity of 5#8s.

$(. t has antioxidant property and may have a role in cancer prevention. E&.

Aniline dye induced bladder cancer.

$1. t may reduce the incidence of cataracts.%efciency maniestations0

$. Scurvy spon&y and sore &ums, loose teeth, anemia, s%ollen Hoints, fra&ile

blood vessels, immune incompetence, delayed %ound healin&, hemorrha&e,

slu&&ish function of adrenal cortex etc. most symptoms are due to impaired

colla&en formation and reduced antioxidant properties.

(. #arlo%Ms disease is infantile form of scurvy

1. "etichiae and echymosis or hematoma due to fra&ile capillaries.

*. Jemorrha&e in conHunctiva, retina haematuria and malena.

2. #ones are fra&ile, brea4 easily and bleedin& into Hoints.

/. Anemia is microcytic hypo chromic. Anemia is due to+. Goss of blood by hemorrha&e

6. Decreased iron absorption

?. Decreased tetrahydrofolic acid

$@. Accumulation of met'hemo&lobin.

%ietary sources amla 7+@@ m&F$@@ &m9 &uava ? 1@@ m&F$@@ &m9 lemon and leafy

ve&etables.

2e(uirement +2 m&Fday pre&nancy , lactation and a&ein& $@@ m&Fday

Thera3eutic uses

$. AdHuvant therapy in infections, T# %ound healin&, burns etc.

(. 8linical dose is 2@@ m& per day1.


17/59

1. What are the coen=yme orms o Vit..1" ive a reaction *here each is

used !on May "#1#

". What are the a&normal meta&olites ound in the urine o 3atients *ith 1"

defciency 873lain ho* olate is tra33ed in 1" defciency and *hat is its

signifcance !on Nov "##/). A 3atient has &een diagnosed as having megalo&lastic anemia.

a. Which vitamin defciency can cause anemia

&. What meta&olites in urine you *ill fnd in this 3atient

c. What is the ste3 in one car&on meta&olism that is aBected in this

case

d. What is the ste3 in 3ro3ionic acid meta&olism that is deective in

this case

,. What are the a&normal meta&olites ound in urine o 3atients *ith 1"


conse(uences. !on Nov "##/. Name the coen=ymes o cyanoco&alamin !on %ec "##1

>. Write &rieGy on the a&sor3tion o vit. 1" !on May "##,

Chemistry o 1" Synonyms are cobalamin, extrinsic factor 7E9 of 8astle. 5ater'

soluble, heat stable and red in color. t is a unique vitamin, synthesi0ed by only

microor&anisms and not by animals and plants.

Structure

$. t contains * pyrole rin&s and a cobalt atom and the structure is called corin

rin& 8orin is lin4ed %ith ben0imida0ole rin& and no% called cobalamin. The

corin rin& is similar to the tetrapyrrole rin& structure of heme(. 8yanide is added to the ! position to be called cyano cobalamin. t is a

laboratory compound.

1. 5hen hydroxyl &roup is added to ! position, hydroxy cobalamin is obtained

%hich is #$(.

*. nside the cells theses &roups are removed and deoxy adenosyl cobalamin is

formed %hich is the stora&e form.

2. 5hen methyl &roup replaces adenosyl &roup, methyl cobalamin is formed

%hich is the circulatin& form. Adenosyl cobalamin and methyl cobalamin are

the functional coen0ymes.

A&sor3tion o 1"0$. Dietary source of #$( is called extrinsic factor of 8astle. )itamin #$( is

absorbed from leum for its absorption it requires

(. "resence of J8l, and

1. ntrinsic factor 79 of 8astle, a constituent of normal &astric Huice.

*. 8obalophilin A bindin& protein secreted in the saliva.

2. Co&alo3hilin ;astric acid and pepsin release the vitamin #$( from protein

bindin& in food and ma4e it available to bind to cobalophilin, a bindin&

protein secreted in the saliva. n the duodenum, cobalophilin is hydroly0ed,

releasin& the vitamin for bindin& to intrinsic factor.

(/1


18/59

/. Intrinc actor The parietal cells of stomach secretes a special protein called

intrinsic factor of 8astle 7l9. lt is a &lycoprotein 76'$2I carbohydrate9 %ith a

molecular %ei&ht around 2@,@@@. ntrinsic factor is resistant to proteolytic

di&estive en0ymes. l &enerally forms a dimer, binds stron&ly %ith $ or (

moles of vitamin #$(. This bindin& protects vitamin #$( a&ainst its upta4eand use by bacteria.

Mechanism a&sor3tion

$. )itamin #$( is absorbed from the distal third of the ileum via specic bindin&

site 7receptors9 that binds the #$(' complexU. The removal of #$( from

Vintrinsic factor3 79 in presence of 8aOO ions and a releasin& factor 7!9

secreted by duodenum ta4e place and #$( enters the ileal mucosal cells for

absorption into the circulation.

(. t is also sho%n that a small amount, about $ to 1I may be absorbed by

simple di=usionU.

1. Trans3ort n the mucosal cells, #$( is converted to methyl cobalamin . lt isthen transported in the circulation in a bound form to proteins namely

transcobalamins 7T8' W T8'll9.

*. Storage #$( is an exception that it is stored.


19/59

(. The metabolism of odd chain fatty acids, valine, isoleucine, methionine and

threonine leads to the production of methyl malonyl 8oA.


20/59

infarction. So, #$( and folic acid are protective a&ainst ischemic heart

disease.

1. #$( deciency results in decreased folate coen0ymes that leads to reduced

nucleotide and D:A svnthesis causin& me&aloblastic anemia.

*. Demyelination

2. n vitamin #$( deciency, due to the non'availability of active methioninemethylation of phosphatidyl ethanolamine to phosphatidyl choline is not

adequate. This leads to decient formation of myelin sheaths of nerves,

resultin& in demyelination and neurolo&ical lesions.

/. Subacute combined de&eneration Dama&e to nervous system is seen in #$(

deciency 7but not in folate deciency9. There is demyelination a=ectin&

cerebral cortex as %ell as dorsal column and pyramidal tract of spinal cord.

Since sensory and motor tracts are a=ected, it is named as combined

de&eneration. Symmetrical paresthesia of extremities, alterations of tendon

and deep senses and rePexes, loss of position sense, unsteadiness in &ait,

positive !omber&Ms si&n 7fallin& %hen eyes are closed9 and positive#abins4iMs si&n 7extensor plantar rePex9 are seen.

+. Achlorhydria Absence of acid in &astric Huice due to atrophic &astritis, is

associated %ith vitamin #$( deciency.


$. Serum #$( estimation by radio'immuno'assay or by EGSA.

(. Schilling5s test

1. The test is for assessin& %eather #$( absorption from the &ut is normal. t is

done in t%o sta&es.

*. Sta&e !adioactive labelled 78obalt'/@9 vitamin #$(, one micro&ram is

&iven orally. Simultaneously an intramuscular inHection of unlabeled vitamin#$( is &iven to saturate tissues %ith normal vitamin #$( and radioactive

vitamin #$( %ill not bind to body tissues. Therefore, the entire absorbed

radioactivity %ill pass into the urine. The patient3s urine is then collected

over the next (* hours to assess the absorption.

2. n patients %ith pernicious anemia or %ith deciency due to impaired

absorption, less than 2I of the radioactivity is detected in urine.

/. Sta&e f an abnormality is found, the test is repeated, %ith radioactive

vitamin plus intrinsic factor &iven orally, and urine is collected for (* hours.

n pernicious anemia, there is lac4 of intrinsic factor, so that the rst test is

abnormal but the second test is normal.+. n #( deciency, methyl melonic acid is excreted in urine.

6.


21/59

". Which vitamin defciency can cause anemia

"ernicious anemia arises %hen vitamin #$( deciency impairs the metabolism of

folic acid, leadin& to functional folate deciency that disturbs erythropoiesis,

causin& immature precursors of erythrocytes to be released into the circulation

7me&aloblastic anemia9.). What meta&olites in urine you *ill fnd in this 3atient

$.


22/59

c.


23/59

iv.

Jydroxymethyl &roup

v.


24/59

histidine is &iven, the excretion of Vi&lu3 in urine is increased further 7Jistidine

loadin& test9.

(. "eripheral smear sho%s ma&aloblasts

1. Crinary excretion of amino imida0ole carboxamide ribosyl'2'phoaphate 7A8A!92%A (@@ micro&ramFday *@@ in pre&nancy and 1@@ in lactation.

Thera3eutic doses

$. $ m&Fday oral. n microcytic anemia folic acid alone if &iven %ill precipitate

neurolo&i'cal manifestations of #$(. So combined therapy is necessary.

(. olic acid can partially reverse the hematolo&ic abnormalities of #$( deciency

and, therefore, can mas4 a cobalamin deciency. Thus, therapy of me&aloblastic

anemia is often initiated %ith folic acid and vitamin #$( until the cause of the

anemia can be determined.

+olate antagonists0

$. 8ompetitive inhibition of en0yme that incorporates "A#A into dihydropteroic acidby sulphona mides is used for its antibacterial e=ects.

(. "yrimethamine is antifolate a&ent used as an antimalarial dru&.

1. Aminopterin and Amethopterin are are po%erful inhibitors of folate reductase

and TJA &eneration. Thus these dru&s decrease the D:A formation and cell

division. They are %idely used as anticancer dru&s, especially for leu4emias and

choriocarcinomas. olinic acid 7citrovorum factor9 is &iven to rescue the patient

from toxicity of methotrexate used in cancer therapy.

!ANT9T:8NIC ACI%

Chemistry0 it consists of t%o components, pantoic acid and b'alanine, held to&ether bypeptide lin4a&e. lt has important metabolic role as coen0yme A.

Coen=yme A ormation "antothena is rst phosphorylated to and then 8ysteine is

added. Steps as follo%s

(+@


25/59

iochemical unctions0

$. The functions of pantothenic acid are exerted throu&h coen0yme A or 8oA

%hich is a central molecule involved in all the metabolisms 7carbohydrate,

lipid and protein9.

(. 5hen bound to acetyl unit, it is called acetyl 8oA. 5ith succinate, succinyl

8oA is formed. J


26/59

%efciency sym3toms usually no symptoms occur due to %ide availability of vitamins

in natural sources ;opalanMs burnin& feet syndrome is reported to be one disease due

to its deciency.

I9TIN

Chemistry0

$. #iotin is a %ater'soluble vitamin that is &enerally classied as a #'complex

vitamin.

(. #iotin is required by all or&anisms but can be synthesi0ed only by bacteria,

yeasts, molds, al&ae, and some plant species

1. #iotin a heterocyclic sulfur containin& monocarboxylic acid. t consists of imida'

0ole and thiophene rin& fused to&ether %ith valeric acid side chain. #iotin is

covalently bound to 'amino &roup of lysine to form biocytin in the en0ymes.

#iocytin nray be re&arded as the coen0yme of biotin.Coen=yme +unctions0

$. 8arbohydrate #iotin serves as a carrier of 8( in the follo%in& carboxylation

reactions

(. !yruvate car&o7ylase converts pyruvate to oxaloacetate in &luconeo&enesis.

#iotin' en0yme complex reacts %ith 8( in the presence of AT" to form

carboxybiotin N en0yme complex. This transfers 8( to pyruvate to form

oxaloacetate required for citric acid cycle.

1. atty acid synthesis Acetyl-CoA car&o7ylase I and II cataly0e the bindin& of

bicarbonate to acetyl' 8oA to form malonyl'8oA.


27/59

1. Avidin'biotin system is commonly utili0ed for detection of patho&ens in the EGSA

test

2%A $@@'1@@ m&Fday in addition to contributions by intestinal bacteria.

Sources liver, 4idney, e&& yol4, mil4, tomatoes and &rains.

%efciency$. Althou&h overt biotin deciency is very rare, the human requirement for dietary

biotin has been demonstrated in t%o di=erent situations prolon&ed intravenous

feedin& 7parenteral9 %ithout bio tin supplementation .

(. Evidence of deciency

1. Ji&h excretion of 1'hydroxyisovaleric acid that rePects decreased activity of the

biotin' dependent en0yme, methylcrotonyl'coa carboxylase

*. !educed urinary excretion of biotin

2. "ropionyl'coa carboxylase activity in peripheral blood lymphocytes

>. Signs and sym3toms

+. Anemia, loss of appetite, nausea, dermatitis, &lossiti etc.6. Jair loss and a scaly red rash around the eyes, nose, mouth, and &enital area.

?. :eurolo&ic symptoms in adults have included depression, lethar&y,

hallucination, and numb ness and tin&lin& of the extremities.

!J2I%9KIN8

1. What are the sources and &iochemical unctions o 3yrido7ine

". Why does the dietary re(uirement o 3yrido7in increase *ith high

3rotein diet !on May "#1#

). +unctions o 3yrido7in *ith t*o e7am3les. !on May "#1)

,. %escri&e the sources' daily re(uirement' meta&olic unctions anddefciency maniestations o !yrido7ine. !on May "#1,

Chemistry

$. )it.#/ collectively represent three compounds namely pyridoxine, pyridoxal and

pyridoxamine . They are pyridine derivatives. "yridoxine is an alcohol, pyridoxal

is an aldehyde and pyridoxamine is an amine.

(. 8oen0yme is pyridoxal phosphate. t is synthesi0ed from all three forms. t is

synthesi0ed by pyridoxal 4inase, utili0in& AT".

Coen=yme unctions0

1. t acts in many reactions of amino acid metabolism.

". Synthesis of certain speciali0ed products such as serotonin, histamine W niacin.

). There is evidence that requirement of )itamin #/ is increased due to increased

dietary protein inta4e, as it is involved as coen0yme in many metabolic reactions

of amino acid metabolism. "yridoxal phosphate participates in reactions li4e

transamination, decarboxylation, deamination, transsulfuration W condensation

reactions of aminoacids.

,. Transamination E&. transaminase converts aminoacids to 4eto acids %ith ""G

actin& as coen0yme. The 4eto acids enter the citric acid cycle and &et oxidi0ed

to &enerate ener&y.

Alanine O Alpha 4eto &lutarate "yruvate O ;lutamic acid 7En0yme Alanine

transaminase9.

(+1


28/59

. %ecar&o7ylation0 examples

a. Tryptophan is rst converted to 2'hydroxy tryptophan and then

decarboxylated to serotonin in the presence of "G".

b. Jistidine is converted to histamine in the presence of "G".

c. ;lutamate is converted to ;ama amino butyric acid by similardecarboxylase reaction %ith "G".

d. 8atecholamines are synthesi0ed from tyrosine by decarboxylase and "G".

>. Sulur Containing Amino Acids ; Transulfuration9 "G" plays an important role

in methionine and cysteine metabolism

a. Jomocysteine O Serine 8ystathionine. 7En0yme 8ystathionine

synthase9

b. 8ystathionine Jomoserine O 8ysteine 7En0yme 8ystathionase9

/. In heme synthesis0 "G" is required for the condensation of succinyl 8oA and

&lycine to form delta amino levulinic acid 7AGA9. n #/ deciency, anemia may

be seen.L. In deamination reactions dehydratase en0yme converts serine to pyruvate in

the presence of "G".

$. "yridoxal phosphate is required for the synthesis of niacin rom try3to3han

i.e0 8oen0yme for 4ynureninase. This is instance in %hich one vitamin

synthesi0es another vitamin.

1#.Jydroxymethyltransferase converts serine to a'4eto&lutarate %ith "G".

11.ther important functions of "G"

a. Synthesis of sphin&olipid and myelin formation.

b. Absorption of amino acid from intestines

c. ormation of 8oen0yme Ad. #oostin& immune functions

e. "reventin& urinary stone formation

f. Ctili0ation of unsaturated fatty acids.

2%A

('(.( m&Fday (.2 in pre&nancy and lactation and elderly.

Sources

E&& yol4, sh, mil4, meat, %heat, corn, cabba&e, roots and tubers. !ich sources

are yeast, rice polishin&, %heat &erms, cereals, le&umes 7pulses9, oil seeds, e&&,

mil4, meat, sh and &reen leafy ve&etables.

%efciency0$. Severe deciency of vitamin #/ is uncommon.

(. :eurolo&ical

1. n the early $?2@s, sei0ures %ere observed in infants as a result of severe

vitamin #/ deciency caused by an error in the manufacture of infant formula.

Abnormal electroencephalo&ram 7EE;9 patterns have been noted in some

studies of vitamin #/ deciency.

*. 8onvulsions in infants have been attributed to pyridoxine deciency. t is

related to lo%ered activity of ;lutamic acid decarboxylase, for %hich pyridoxal "

is a coen0yme. As a result there occurs lo%erin& of X'amino butyric acid 7;A#A9

in the brain %hich causes convulsions.

(+*


29/59

2. ther neurolo&ic symptoms noted in severe vitamin #/ deciency include

irritability, depression, and confusion additional symptoms include inPammation

of the ton&ue, sores or ulcers of the mouth, and ulcers of the s4in at the corners

of the mouth.

/. Jypo chromic microcytic anemia.+. Deciency state is indicated by increased excretion of xanthurenic acid in urine

6. Dru& induced deciency occurs in sonia0id, d'pencillamine therapy. #/

deciency has been observed in humans durin& the treatment of tuberculosis

%ith hi&h doses of tuberculostatic dru& sonicotinic acid hydra0ide or sonia0id

7:J9.t is believed that isonia0id forms a Vhydra0one complex3 %ith pyridoxine,

resultin& in incomplete activation of the vitamin. Durin& penicillamine treatment,

the dru& reacts %ith pyridoxal'" to form inactive thia0olidine derivative.

?. 0

$. )it #/ is used in mornin& sic4nessU, radiation sic4ness, muscular dystrophies,

treatment of hyperoxaluria, and recurrin& oxalate stones of 4idney, and mild

forms of pyridoxine deciency have been reported to occur sometimes in %omen

ta4in& oral contraceptives containin& oestradiol.

(. Dutch researchers and reported in neurolo&y that a hi&her inta4e of vitamin #/

may decrease the ris4 of "ar4inson3s disease.To7icity0

Excess use of vitamin 6/ B.2 &Fday9 in the %omen of premenstruasl yndromei s

associated %ith sensory neuropathy. Some %or4ers have su&&estedth at vitamin

6/ more than (@@ m&Fday may cause neurolo&ical dama&e.

T:IAMIN8 ;VITAMIN 1<

1. Meta&olic role thiamine in the &ody. !on May "##$

". Measurement o *hole &lood or erythrocyte trans6etolase activity is used

as a &iochemical mar6er to assess &eri&eri. What is the &asis o this !on

Nov "##>

). Which en=yme in 2C is measured in thiamine defciency Name the other

en=ymes that re(uire thiamine or their activity. !on %ec "##"

,. ive the Co en=yme orms o thiamine. !on May "##

. Write a note on &eri&eri. !on Nov "#1#

>. What are the meta&olic roles o thiamine in the &ody !on May "##$

Synonyms Antiberiberi factor, antineuritic vitamin, aneurin.

8oen0yme thiamine 3yro3hos3hate ;T!!<

Chemistry0

(+2


30/59

Thiamine contains a substituted pyrimidine rin& connected to a substituted

thia0ole rin& by means of methylene brid&e. t contains sulphur 7sulphur

containin& vitamin9. The vitamin is then converted to its active co'en0yme form

by additionof t%o phosphate &roups, %ith the help of AT". t is cataly0ed by

thiamine pyrophosphotransferase.iosynthesis0

Synthesised by plants, yeasts and bacteria. :ot synthesised by human bein&s,

hence should be supplied in diet. ntestinal bacterial Pora can synthesise the

vitamin.

Meta&olic roles0

$. The main role of thiamine 7T""9 is in carbohydrate metabolism. So, the

requirement of thiamine is increased alon& %ith hi&her inta4e of carbohydrates

(. !yruvate dehydrogenase The co'en0yme form is thiamine pyrophosphate

7T""9. t is used in oxidative decarboxylation of alpha 4eto acids, e.&. pyruvate

dehydro&enase cataly0es the brea4do%n of pyruvate, to acetyl 8oA and carbon

dioxide.

1. Al3ha 6etoglutarate dehydrogenase Another reaction that requires T"" is

the oxidative decarboxylation of alpha 4eto&lutarate to succinyl 8oA and 8(.

*. Trans6etolase The second &roup of en0ymes that use T"" as co'en0yme are

the trans4etolases, in the hexose monophosphate shunt path%ay of &lucose.

2. The branched chain a'4eto acid dehydro&enase 7decarboxylase9 catalyses the

oxidative decarboxylation of branched chain amino acids 7valine, leucine and

isoleucine9 to the respective 4eto acids. This en0yme also requires T"".

/. #$ is also required in amino acid Tryptophan metabolism for the activity of the

en0yme Tryptophan pyrrolase.

(+/


31/59

+. T"" plays an important role in the transmission of nerve impulse. lt is believed

that T"" is required for acetylcholine synthesis and the ion translocation of

neural tissue.

%efciency Maniestations o Thiamine0

$. n thiamine deciency, the activity of dehydro&enase'cataly0ed reactionsvis aredecreased, resultin& in a decreased production of AT" leadin& to impaired

cellular function. This can result in three distinct syndromes

(. A chronic peripheral neuritis, beriberi, %hich may or may not be associated %ith

heart failure and edema

1. Acute pernicious 7fulminatin&9 beriberi 7shoshin beriberi9, in %hich heart failure

and metabolic abnormalities predominate, %ithout peripheral neuritis

*. 5ernic4e encephalopathy %ith Korsa4o= psychosis, %hich is associated

especially %ith alcohol and narcotic abuse.

2. eri&eri0 This is a severe thiamine'deciency syndrome found in areas %here

polished rice is the maHor component of the diet. t is characterised by thefollo%in& manifestations

/. 8) These include palpitation, dyspnoea, cardiac hypertrophy and dilatation,

%hich may pro&ress to con&estive cardiac failure.

+. :eurolo&ical manifestations

6. These are predominantly those of ascendin&, symmetrical, peripheral

polyneuritis.

?. "olyneuritis common in chronic alcoholics. Alcohol utili0ation needs lar&e doses

of thiamine. Alcohol inhibits intestinal absorption of thiamine, leadin& to

thiamine deciency. "olyneuritis may also be associated %ith pre&nancy and old

a&e. Thiamine deciency may cause impairment of conversion of pyruvate toacetyl 8oA. This results in increased plasma concentration of pyruvate and

lactate, leadin& to lactic acidosis.

$@. 5ernic4e3s encephalopathy This is seen primarily in association %ith chronic

alcoholism and is due to dietary insu-ciency or impaired intestinal absorption of

the vitamin. t is characteri0ed by ophthalmople&ia, nysta&mus, cerebellar

ataxia.

$$. Some alcoholics develop 5ernic4e' Korsa4o= psychosis syndrom characteri0ed

by apathy, loss of memory, ataxia, and a rhythmic to'and'fro motion of the

eyeballs 7nysta&mus9.

$(. The neurolo&ic consequences of 5ernic4eMs syndrome are treatable %iththiamine supplementation.

$1. ; symptoms Amon&st these, anorexia is an early symptom. There may be

&astric atony, %ith diminished &astric motility and nausea fever and vomitin&

occur in advanced sta&es.

$*. Dry beriberi 5hen it is not associated %ith oedema.

$2. 5et beriberi edema is associated. t is probably in part to con&estive cardiac

failure and in part to protein malnutrition 7Go% plasma albumin9.

$/. nfantile beriberi t occurs in infants born to mothers su=erin& from thiamine

deciency. Si&ns of infantile beriberi include restlessness and sleeplessness

tachycardia, vomitin&, convulsions, and, if not treated, death.

iochemical !arameters

(++


32/59

$. n thiamine deciency, blood thiamine is reduced, but pyruvate, alpha

4eto&lutarate and lactate are increased.

(. 8rythrocyte trans6etolase activity is reduced %ith accumulation of pentose

su&ars this is the earliest manifestation seen even before clinical disturbances.


33/59

1. "rotein metabolisn

a. ;lycine oxidase ;lycine ;lyoxylate O :J1

b. D NAmino acid oxidase D'Amino acid a'Keto acid O :J1

*. "urine metabolism

a. >anthine oxidase >anthine ' Cric acid2. ADJ( %hen oxidi0ed in the electron transport chain %ill &enerate $ $F( AT"

molecules

+MN de3endent reactions0

$. G'Amino acid oxidase G'Amino acid' '''''' a 'Keto acid O :Jo

(. n the respiratory chain, the :ADJ dehydro&enase contains


34/59

1. Except mehyl &roup others are carried by tetrahydrofolic acid. They are contributed

by by amino ac'ids

*. 8o( is also a one carbon unit as it participates in carboxylation but not accepted by

many as a one arbon unit.

+ormation o one car&on units0$. The formate released from &lycine and tryptophan metabolism combines %ith

TJ to form :$@' formyl TJ.

(. Jistidine contributes formimino fra&ment to produce :2'formimino TJ

1. 5hen serine is converted into &lycine :2':$@ methylene TJ is formed.

*. 8holine and betain contribute to the formation of :2'methyl TJ. 8holine and

betaine are donors of hydroxy methyl &roups. As serine is converted to choline,

1 one'carbon units are used up. Durin& the conversion of choline to &lycine,

these methyl &roups are recovered. Jence, this path%ay is called the Lsalva&e

path%ayL for one'carbon units.

tili=ation o one car&on moiety0ne carbon units are used to synthesise the follo%in& compounds

$. 8( of purine

(. ormylation of


35/59

VITAMIN

1. What is the role o Vit. in maintaining &ody haemostasis !on May "##$

". What are the &iological unctions o Vit. !on May "#1"

). State the unction o Vit. E 8. !on May "##$

,. Name the Vit. de3endant coagulation actors. What is the role o Vit. on

their activities !on Nov "##/F May "##)

. Sym3toms o Vit. defciency are met *ith more due to liver dysunction

than due to lac6 o the vitamin. 873lain *hy this is so. !on a3r "##"

$. )itamin K is a fat'soluble vitamin. The LKL is derived from the ;erman %ordL4oa&ulation. There are t%o naturally occurrin& forms of vitamin K.

(6$


36/59

a. "lants synthesi0e phylloquinone, %hich is also 4no%n as vitamin 1.

b. #acteria synthesi0e vitamin "' desi&nated as menaquinone.

c. ) is a synthetic form.

(. 8hemistry they are napthoquinone derivatives %ith isoprenoid side chain.

1. Absorption )it K provided by diet or bacterial synthesis is absorbed in association%ith chylomicrons %ith the help of bile salts. t is transported %ith GDG and stored in

liver.

*. #iochemical functions

a. )itamin K is necessary for coa&ulation. t brin&s about posttranslational

modication clottin& factors (,+,? and $@ produced as 0ymo&en in liver.

b. Vit. acts as coen=yme or the car&o7ylation o glutamic acid &y

en=yme car&o7ylase. ;amma carboxy&lutamate is formed %hich is critical

to the calcium'bindin& function of these proteins. They are ne&atively

char&ed 78'9 and they combine %ith positively char&ed calcium ions

78a(O9 to form a complex. The complex 7e&. prothrombin ' 8a9 binds to thephospholipids on the membrane surface of the platelets. This leads to the

increased conversion of prothrombin to thrombin.

b. The formation of y'carboxy&lutamate is inhibited by dicumarol, an

anticoa&ulant and %arfarin, a synthetic analo&ue and they can inhibit

vitamin K action.

c. The mineral'bindin& capacity of osteocalcin in bone also requires vitamin K'

dependent &amma'carboxylation of &lutamic acid residues.

d. )it.K is also involved in ET8 and oxidative phosphorylation.

2. !DA adult +@'$*@ micro&ramFday

/. Sources 8abba&e, cauliPo%er, tomatoes, spinach, alfa'alfa, &reen ve&etables, e&&yol4, meat, liver, cheese and mil4 products.

+. 8auses for Deciency of )itamin K

a. n normal adults dietary deciency seldom occurs since the intestinal

bacterial synthesis is su-cient to meet the needs of the body. Jo%ever

deciency can occur in conditions of malabsorption of lipids. This can result

from obstructive Haundice, chronic pancreatitis, sprue, etc.

b. "rolon&ed antibiotic therapy and &astrointestinal infections %ith diarrhoea

%ill destroy the bacterial Pora and can also lead to vitamin K deciency.

6. Deciency symptoms

a. vert vitamin K deciency results in impaired blood clottin&, usuallydemonstrated by laboratory tests that measure clottin& time.

b. Jemorrha&ic disease of the ne%born is due to vitamin K deciency. The

ne%borns, especially the premature infants have relative vitamin K

deciency. This is due to lac4 of hepatic stores, limited oral inta4e 7breast

mil4 has very lo% levels, $2 m&Fliter9 and absence of intestinal bacterial

Pora. t is often advised that pre'term infants be &iven prophylactic doses of

vitamin K 7$ m&


37/59

of vitamin K deciency.


38/59

dietary amino acid tryptophan via the 4ynurenine path%ay. Tryptophan produces

quinolinate %hich then forms nicotinate mononucleotide and, ultimately, :ADO and

:AD"O. /@ m& of tryptophan %ould yield $ m& of :iacin.

2. 8o'en0yme ormation of :iacin

a. :iacin is converted to its co'en0yme forms, vi0. :icotinamide adeninedinucleotide 7:ADO9 and :icotinamide adenine dinucleotide phosphate

7:AD"O9.

b. The niacin is attached to a ribose phosphate to form a mononucleotide. t is

then attached to A


39/59

/. "henyl alanine hydroxylase 7"henylalanine tyrosine9

2. :ADJ produced is oxidi0ed in the electron transport chain to &enerate AT". ne

:ADJ molecule is oxidi0ed in the respiratory chain to &enerate 1 molecules of

AT"

/. :AD"J is also important for many biosynthetic reactions as it donates reducin&equivalents

2%A The daily requirement of niacin for an adult is $2'(@ m& and for children, around

$@'$2 m&.


$. 8auses of deciency

a. Tryptophan deciency in diet e&. Stable food containin& sor&hum and

mai0e %here tryptophan is not metabolically available to body.

b. "yridoxal deciency leads to inability to convert tryptophan to niacin.

c. Jartnup disease %here con&enital defect of absorption of tryptophan

from intestine is present.d. 8arcinoid syndrome %here tumor tissue utili0es lar&e amount of

tryptophan for serotonin synthe sis.

e. Dietary sources rich sources are dried yeast, rice polishin&, liver, peanut,

%hole cereals, le&umes, meat and sh.

f. !DA normally (@ m&Fday additional 2 m& for pre&nancy and lactation.

&. Therapeutic uses "harmacolo&ic doses of nicotinic acid, but not

nicotinamide, have been 4no%n to reduce serum cholesterol by reducin&

acetyl 8oA pool. :iacin is commonly prescribed %ith other lipid'lo%erin&

medications.

(. %efcency sym3toms0a. :iacin deciency is mostly seen amon& people %hose staple diet is corn

or mai0e. :iacin present in mai0e is unavailable to the body as it is in

bound form. urther, tryptophan content is lo% in mai0e.

b. !ellagra

i. :iacin deciency leads to the disease called pella&ra

characteri0ed by 1 Ds diarrhea, dermatitis and de mentia.

ii. Dermatitis consists of bri&ht erythema in feet, an4les and face

pi&mentation around the nec4 is called 8asal3s nec4lace. The

dermatitis is precipitated by exposure to sunli&ht.

iii. Symptoms related to the di&estive system include a bri&ht redton&ue, vomitin&, and diarrhea.

iv. Dementia occurs in chronic cases and ataxia and spasticity could

also occur.

v. :eurolo&ic symptoms also include headache, apathy, fati&ue,

depression, disorientation, and memory loss. f untreated, pella&ra

is ultimately fatal.

Thera3eutic uses o niacin0

$. :iacin inhibits lipolysis in the adipose tissue and decreases the circulatory free

fatty acids.

(. Triacyl&lycerol synthesis in the decreased.

1. The serum levels of lo%'density lipoproteins 7GDG9, very lo%'density lipoproteins

(62


40/59

7)GDG9, triacyl&lycerol and cholesterol are lo%ered. Jence niacin is used in the

treatment of hyperlipoproteinemia type b 7elevation of GDG and )GDG9.

To7icity0

*. ;lyco&en and fat reserves of s4eletal and cardiac muscle are depleted.

1. There is a tendency for the increased levels of &lucose and uric acid in thecirculation.

ASC92IC ACI%

1. Write the sources' re(uirements' defciency maniestations' &iochemical

actions o Vit.C !on a3r "###

". Vit C 3lays a role in 3ost translational modifcation- Dusty. !on %ec "##)

). 873lain the role o ascor&ic acid in 3ost translational modifcation. !on

May "##/

Chemistry0

$. Ascorbic acid is a %ater soluble vitamin destroyed by heat, al4ali and on

stora&e. +@Iis lost %hile coo4'in& inactivated if coo4ed in copper vessel.

(. 8hemistry t is a hexose and closely resemble monosaccharide t has enolic

hydroxyl &roup it is acidic and a stron& reducin& a&ent G'ascorbic acid and

dehydroascorbic acid are active forms D'ascorbic acid is an inactive form.

1. "lants and animals can synthesis ascorbic acid from &lucose via uronic acid

path%ay.


41/59

2. t enhances iron absorption from the intestines by reducin& ferric form to ferrous

form.

/. t helps in reconversion of met'hemo&lobin to hemo&lobin.

+. t helps maturation of !#8 by involvin& in folate reductase that converts folic

acid to tetra folic acid.6. ts presence in adrenal cortex indicates that it is necessary for the synthesis of

steroids.

?. t helps bile acid synthesis form cholesterol.

$@. "romotes pha&ocyic activity of 5#8s.

$$. t has antioxidant property and may have a role in cancer prevention. E&. Aniline

dye induced bladder cancer.

$(. t may reduce the incidence of cataracts.


$. Scurvy spon&y and sore &ums, loose teeth, anemia, s%ollen Hoints, fra&ile blood

vessels, immune incompetence, delayed %ound healin&, hemorrha&e, slu&&ishfunction of adrenal cortex etc. most symptoms are due to impaired colla&en

formation and reduced antioxidant properties.

(. #arlo%Ms disease is infantile form of scurvy

1. "etichiae and echymosis or hematoma due to fra&ile capillaries.

*. Jemorrha&e in conHunctiva, retina haematuria and malena.

2. #ones are fra&ile, brea4 easily and bleedin& into Hoints.

/. Anemia is microcytic hypo chromic. Anemia is due to

a. Goss of blood by hemorrha&e

b. Decreased iron absorption

c. Decreased tetrahydrofolic acidd. Accumulation of met'hemo&lobin.

%ietary sources amla 7+@@ m&F$@@ &m9 &uava ? 1@@ m&F$@@ &m9 lemon and leafy

ve&etables.

2e(uirement +2 m&Fday pre&nancy , lactation and a&ein& $@@ m&Fday

Thera3eutic uses

a. AdHuvant therapy in infections, T# %ound healin&, burns etc.

b. 8linical dose is 2@@ m& per day

c.


42/59

). A 3atient has &een diagnosed as having megalo&lastic anemia.

a. Which vitamin defciency can cause anemia

&. What meta&olites in urine you *ill fnd in this 3atient

c. What is the ste3 in one car&on meta&olism that is aBected in this

cased. What is the ste3 in 3ro3ionic acid meta&olism that is deective in

this case

,. What are the a&normal meta&olites ound in urine o 3atients *ith 1"


conse(uences. !on Nov "##/

. Name the coen=ymes o cyanoco&alamin !on %ec "##1

>. Write &rieGy on the a&sor3tion o vit. 1" !on May "##,

Chemistry o 1"

$. Synonyms are cobalamin, extrinsic factor 7E9 of 8astle. 5ater'soluble, heat stableand red in color. t is a unique vitamin, synthesi0ed by only microor&anisms and not

by animals and plants.

(. Structure

a. t contains * pyrole rin&s and a cobalt atom and the structure is called corin

rin& 8orin is lin4ed %ith ben0imida0ole rin& and no% called cobalamin. The

corin rin& is similar to the tetrapyrrole rin& structure of heme

a. 8yanide is added to the ! position to be called cyano cobalamin. t is a

laboratory compound.

b. 5hen hydroxyl &roup is added to ! position, hydroxy cobalamin is obtained

%hich is #$(.c. nside the cells theses &roups are removed and deoxy adenosyl cobalamin is

formed %hich is the stora&e form.

d. 5hen methyl &roup replaces adenosyl &roup, methyl cobalamin is formed

%hich is the circulatin& form. Adenosyl cobalamin and methyl cobalamin are

the functional coen0ymes.

A&sor3tion o 1"0

$. Dietary source of #$( is called extrinsic factor of 8astle. )itamin #$( is absorbed

from leum for its absorption it requires

a. "resence of J8l, and

b. ntrinsic factor 79 of 8astle, a constituent of normal &astric Huice.a. 8obalophilin A bindin& protein secreted in the saliva.

(. Co&alo3hilin ;astric acid and pepsin release the vitamin #$( from protein bindin&

in food and ma4e it available to bind to cobalophilin, a bindin& protein secreted in

the saliva. n the duodenum, cobalophilin is hydroly0ed, releasin& the vitamin for

bindin& to intrinsic factor.

1. Intrinc actor The parietal cells of stomach secretes a special protein called

intrinsic factor of 8astle 7l9. lt is a &lycoprotein 76'$2I carbohydrate9 %ith a

molecular %ei&ht around 2@,@@@. ntrinsic factor is resistant to proteolytic di&estive

en0ymes. l &enerally forms a dimer, binds stron&ly %ith $ or ( moles of vitamin

#$(. This bindin& protects vitamin #$( a&ainst its upta4e and use by bacteria.

*. Mechanism a&sor3tion )itamin #$( is absorbed from the distal third of the ileum

(66


43/59

via specic bindin& site 7receptors9 that binds the #$(' complexU. The removal of

#$( from Vintrinsic factor3 79 in presence of 8aOO ions and a releasin& factor 7!9

secreted by duodenum ta4e place and #$( enters the ileal mucosal cells for

absorption into the circulation.

2. t is also sho%n that a small amount, about $ to 1I may be absorbed by simpledi=usionU.

/. Trans3ort n the mucosal cells, #$( is converted to methyl cobalamin . lt is then

transported in the circulation in a bound form to proteins namely transcobalamins

7T8' W T8'll9.

+. Storage #$( is an exception that it is stored.


44/59

TJ pool. The outcome is the development of me&aloblastic anemia.

Administration of the amino acid methionine has been sho%n to partially

correct the symptoms of #$( deciencies. This is due to the fact that the

formation of :2'methyl TJ is inhibited by S'adenosylmethionine. A

combined therapy of vitamin #$( and folic acid is &enerally employed totreat the patients %ith me&aloblastic anemia.

Causes o 1" defciency0

$. )itamin #$( is found only in foods of animal ori&in, and no plant sources. Strict

ve&etarians 7ve&ans9 are at ris4 of developin& #$( deciency.

(. nly source is curd and mil4 %hich may not be available poor people.

1. "artial or total &astrectomy'these individuals become intrinsic factor decient

*. !ernicious anemia0 t is manifested usually in persons over *@ years. t is an

autoimmune disease. ntrinsic factor deciency can occur due to autoimmune

destruction of this %ill lead to malabsorption of #$(. t is characteri0ed by

lo% hemo&lobin levels decreased number of erythrocytes and neurolo&icalmanifestations.

2. Atrophy of &astric epithelium can also occur in iron deciency anemia leadin&

lac4 of .

/. !elative deciency of #$( in pre&nancy

+. ish tape%orm consumes #$( and infection produces #$( deciency.


$. )itamin #$( deciency causes simultaneous folate deciency due to the folate

trap. Therefore all the manifestations of folate deciency are also seen

(. n vitamin #$( deciency convertion of homocystine to methionine is bloc4ed, so

that homocysteine is accumulated, leadin& to homocystinuria. Jomocysteinelevel in blood has a positive correlation %ith myocardial infarction. So, #$( and

folic acid are protective a&ainst ischemic heart disease.

1. #$( deciency results in decreased folate coen0ymes that leads to reduced

nucleotide and D:A svnthesis causin& me&aloblastic anemia.

*. Demyelination

a. n vitamin #$( deciency, due to the non'availability of active methionine

methylation of phosphatidyl ethanolamine to phosphatidyl choline is not

adequate. This leads to decient formation of myelin sheaths of nerves,

resultin& in demyelination and neurolo&ical lesions.

b. Subacute combined de&eneration Dama&e to nervous system is seen in#$( deciency 7but not in folate deciency9. There is demyelination

a=ectin& cerebral cortex as %ell as dorsal column and pyramidal tract of

spinal cord. Since sensory and motor tracts are a=ected, it is named as

combined de&eneration. Symmetrical paresthesia of extremities,

alterations of tendon and deep senses and rePexes, loss of position

sense, unsteadiness in &ait, positive !omber&Ms si&n 7fallin& %hen eyes

are closed9 and positive #abins4iMs si&n 7extensor plantar rePex9 are seen.

2. Achlorhydria Absence of acid in &astric Huice due to atrophic &astritis, is

associated %ith vitamin #$( deciency.


$. Serum #$( estimation by radio'immuno'assay or by EGSA.

(?@


45/59

(. Schilling5s test

a. The test is for assessin& %eather #$( absorption from the &ut is normal.

t is done in t%o sta&es.

b. Sta&e !adioactive labelled 78obalt'/@9 vitamin #$(, one micro&ram is

&iven orally. Simultaneously an intramuscular inHection of unlabeledvitamin #$( is &iven to saturate tissues %ith normal vitamin #$( and

radioactive vitamin #$( %ill not bind to body tissues. Therefore, the

entire absorbed radioactivity %ill pass into the urine. The patient3s urine

is then collected over the next (* hours to assess the absorption.

c. n patients %ith pernicious anemia or %ith deciency due to impaired

absorption, less than 2I of the radioactivity is detected in urine.

d. Sta&e f an abnormality is found, the test is repeated, %ith radioactive

vitamin plus intrinsic factor &iven orally, and urine is collected for (*

hours. n pernicious anemia, there is lac4 of intrinsic factor, so that the

rst test is abnormal but the second test is normal.1. n #( deciency, methyl melonic acid is excreted in urine.

*.


46/59

metabolised to formimino &lutamic acid 7;GC9 from %hich formimino

&roup is removed by TJA. Therefore in folate deciency, ;GC is

excreted in urine.

ii. A8A! excretion n the purine nucleotide synthesis, the last step is the

addition of 8( %ith the help of :$@'formyl TJA. 5hen this is bloc4ed,the precursor, amino imida0ole carboxamide ribosyl'2'phosphate

7A8A!9 accumulates and is excreted in urine.

). What is the ste3 in one car&on meta&olism that is aBected in this case

a. Tetrahydrofolate serves as an acceptor or donor of one carbon units 7formyl,

methyl etc.9 in a variety of reactions involvin& amino acid and nucleotide

metabolism.

b. Tetrahydrofolate is mostly trapped as :s'methyl TJ in %hich form it is

present in the circulation. )itamin #$( is needed for the conversion of :2'

methyl TJ to TJ, in a reaction %herein homocysteine is converted to

methionine. This step is essential for the liberation of free TJ and for itsrepeated use in one carbon metabolism. n #$( deciency, conversion of :s'

methyl TJ to TJ is bloc4ed.

,. What is the ste3 in 3ro3ionic acid meta&olism that is deective in this

case

"ropionyl'8oA is a coen0yme A derivative of propionic acid 7odd chain fatty acid9.

The b'oxidation of saturated fatty acids containin& odd number of carbon atoms

leads to a 1 carbon fra&ment, "ropionyl'8oA %hich is converted tosuccinyl 8oA as

follo%s

a. "ropionyl8 oA is carboxylatedi n the presence of AT", 8( and vitamin

bion to D'methylmalonyl 8oA.b.


47/59

A&sor&tion0 is mainly from HeHunum transported by beta &lobulins and ta4en by liver

not stored in tissues.

Co-en=yme unction

$. olic acid is rst converted to +,6 dihydro folic acid and a&ain into 2,/,+,6

tetrahydro folic acid by :AD"J dependant folate reductase.

(. TJA is a one carbon &roup carrier. TJ serves as an acceptor or donor of one

carbon units in a variety of reactions involvin& amino acid and nucleotide

metabolism. Except methyl &roup others are carried by tetrahydrofolic acid.

They are contributed by amino acids. ne carbon &roups are

a. ormyl &roup

b. ormimino &roup

c.


48/59

&luten induced enteropathy, HeHunal resection, &astroileostomy etc.

1. Anticonvulsants li4e hydantoin, phenobarbitone etc interfere %ith

&astrointestinal en0ymes and reduce the conversion of poly&lutamate form of

folate into mono&lutamate form %hich can be absorbed.

*. !elative deciency occurs in hemolytic anemia as the demand is more.

2. Diet poor in folate./. olate trap.


$. Deciency a=ects D:A synthesis as thymidylate synthase en0yme is inhibited.

(.

b. Ans n the metabolism of the amino acid histidine there is folic acid

dependent step at the point %here formimino'&lutamic acid 7i&luU9 is

converted to &lutamic acid. n folic acid decient patients, this reaction

cannot be carried out, as a result, &luU accumulates in the blood and

excreted in urine. i&lu excretion in urine is an index of folic acid

deciency. 5hen a loadin& doseU of histidine is &iven, the excretion ofVi&lu3 in urine is increased further 7Jistidine loadin& test9.

1. "eripheral smear sho%s ma&aloblasts

*. Crinary excretion of amino imida0ole carboxamide ribosyl'2'phoaphate 7A8A!9

2%A (@@ micro&ramFday *@@ in pre&nancy and 1@@ in lactation.

Thera3eutic doses

$. $ m&Fday oral. n microcytic anemia folic acid alone if &iven %ill precipitate

neurolo&i'cal manifestations of #$(. So combined therapy is necessary.

(. olic acid can partially reverse the hematolo&ic abnormalities of #$( deciency

and, therefore, can mas4 a cobalamin deciency. Thus, therapy of me&aloblastic

anemia is often initiated %ith folic acid and vitamin #$( until the cause of the

anemia can be determined.

+olate antagonists0

$. 8ompetitive inhibition of en0yme that incorporates "A#A into dihydropteroic acid

by sulphona mides is used for its antibacterial e=ects.

(?*


49/59

(. "yrimethamine is antifolate a&ent used as an antimalarial dru&.

1. Aminopterin and Amethopterin are are po%erful inhibitors of folate reductase

and TJA &eneration. Thus these dru&s decrease the D:A formation and cell

division. They are %idely used as anticancer dru&s, especially for leu4emias and

choriocarcinomas. olinic acid 7citrovorum factor9 is &iven to rescue the patientfrom toxicity of methotrexate used in cancer therapy.

!ANT9T:8NIC ACI%

Chemistry0 it consists of t%o components, pantoic acid and b'alanine, held to&ether by

peptide lin4a&e. lt has important metabolic role as coen0yme A.

Coen=yme A ormation "antothena is rst phosphorylated to and then 8ysteine is

added. Steps as follo%s

iochemical unctions0

$. The functions of pantothenic acid are exerted throu&h coen0yme A or 8oA %hich

is a central molecule involved in all the metabolisms 7carbohydrate, lipid and

protein9.

(. 5hen bound to acetyl unit, it is called acetyl 8oA. 5ith succinate, succinyl 8oA is

formed. J


50/59

(. a'Keto&lutarate O 8oA''''''''''''''''''''''Succiny 8oA

Thio4inase

1. atty acid O8oA'''''''''''''''''''''''''''''''''''Acyl 8oA

2. Examples of &roup transfer by 8oAa. Acetyl coA O 8holine QR Acetyl 8holine O8oA

b. Acetyl 8oA O xalo acetate QR 8itrate O 8oA

c. Succinyl 8oA O Acetoacetate QR Acetoacetyl 8oA O Succinate

/. !ole of Acetyl 8oA in metabolic inte&ration

a. 8arbohydrates, amino acid and fatty acids metabolism lead to Acetyl 8oA

formation. This in turn enters

i. T8A cycle to release ener&y,

ii. atty acid metabolism to form triacyl &lycerol,

iii. 8holesterol synthesis and its further leadin& to formation of )it. D

and steroids,iv. Ketone path%ays to release ener&y and

v. Detoxication reactions.

b. "antothenic acid itself is component of fatty acid synthase en0yme

complex %hich is involved in fatty acid synthesis.

2%A 2'$@ m&Fday

Sources e&&, liver, meat, yeast, mil4 etc.

%efciency sym3toms usually no symptoms occur due to %ide availability of vitamins

in natural sources ;opalanMs burnin& feet syndrome is reported to be one disease due

to its deciency.

I9TIN

Chemistry0

$. #iotin is a %ater'soluble vitamin that is &enerally classied as a #'complex vitamin.

(. #iotin is required by all or&anisms but can be synthesi0ed only by bacteria, yeasts,

molds, al&ae, and some plant species

1. #iotin a heterocyclic sulfur containin& monocarboxylic acid. t consists of imida'0ole

and thiophene rin& fused to&ether %ith valeric acid side chain. #iotin is covalently

bound to ε'amino &roup of lysine to form biocytin in the en0ymes. #iocytin nray be

re&arded as the coen0yme of biotin.

Coen=yme +unctions0

i. 8arbohydrate #iotin serves as a carrier of 8( in the follo%in& carboxylation

reactions

ii. !yruvate car&o7ylase converts pyruvate to oxaloacetate in

&luconeo&enesis. #iotin' en0yme complex reacts %ith 8( in the presence of

AT" to form carboxybiotin N en0yme complex. This transfers 8( to pyruvate

to form oxaloacetate required for citric acid cycle.

iii. atty acid synthesis Acetyl-CoA car&o7ylase I and II cataly0e the bindin&

of bicarbonate to acetyl' 8oA to form malonyl'8oA.


51/59

certain amino acids, cholesterol, and odd chain fatty acids. "ropionyl 8oA is

converted to methyl malonyl 8oA in the presence of biotin.

v. Methylcrotonyl-CoA car&o7ylase cataly0es an essential step in the

catabolism of leucine, an essen tial amino acid. n this reaction b'"ropionyl

8oA is converted to b'methyl &lutaconyl 8oA .vi. :istone &iotinylation0 #iotinylation of histones plays a role in re&ulatin&

D:A replication and transcription as %ell as cellular proliferation and other

cellular responses.

vii. #iotin'ndependent 8arboxylation !eactions

i. 8arbamoyl phosphate synthetase, %hich is the steppin& stone for

urea and pyrimidine synthesis.

ii. Addition of 8( to form 8/ in purine rin&.

iii.


52/59

Chemistry

$. )it.#/ collectively represent three compounds namely pyridoxine, pyridoxal

and pyridoxamine . They are pyridine derivatives. "yridoxine is an alcohol,

pyridoxal is an aldehyde and pyridoxamine is an amine.

(. 8oen0yme is pyridoxal phosphate. t is synthesi0ed from all three forms. t is

synthesi0ed by pyridoxal 4inase, utili0in& AT".

Coen=yme unctions0

1. t acts in many reactions of amino acid metabolism.

a. Synthesis of certain speciali0ed products such as serotonin, histamine W

niacin.

b. There is evidence that requirement of )itamin #/ is increased due to

increased dietary protein inta4e, as it is involved as coen0yme in many

metabolic reactions of amino acid metabolism. "yridoxal phosphate

participates in reactions li4e transamination, decarboxylation,

deamination, transsulfuration W condensation reactions of aminoacids.

(. Transamination E&. transaminase converts aminoacids to 4eto acids %ith

""G actin& as coen0yme. The 4eto acids enter the citric acid cycle and &et

oxidi0ed to &enerate ener&y.

Alanine O Alpha 4eto &lutarate "yruvate O ;lutamic acid 7En0yme Alanine

transaminase9.

1. %ecar&o7ylation0 examples

a. Tryptophan is rst converted to 2'hydroxy tryptophan and then

decarboxylated to serotonin in the presence of "G".

b. Jistidine is converted to histamine in the presence of "G".c. ;lutamate is converted to ;ama amino butyric acid by similar

decarboxylase reaction %ith "G".

d. 8atecholamines are synthesi0ed from tyrosine by decarboxylase

and "G".

*. Sulur Containing Amino Acids ; Transulfuration9 "G" plays an important

role in methionine and cysteine metabolism

a. Jomocysteine O Serine 8ystathionine. 7En0yme 8ystathionine

synthase9

b. 8ystathionine Jomoserine O 8ysteine 7En0yme 8ystathionase9

2. In heme synthesis0 "G" is required for the condensation of succinyl 8oAand &lycine to form delta amino levulinic acid 7AGA9. n #/ deciency, anemia

may be seen.

/. In deamination reactions dehydratase en0yme converts serine to pyruvate

in the presence of "G".

+. "yridoxal phosphate is required for the synthesis of niacin rom

try3to3han i.e0 8oen0yme for 4ynureninase. This is instance in %hich one

vitamin synthesi0es another vitamin.

6. Jydroxymethyltransferase converts serine to a'4eto&lutarate %ith "G".

?. ther important functions of "G"

i. Synthesis of sphin&olipid and myelin formation.ii. Absorption of amino acid from intestines

iii. ormation of 8oen0yme A

(?6


53/59

iv.

#oostin& immune functions

v. "reventin& urinary stone formation

vi. Ctili0ation of unsaturated fatty acids.

2%A

('(.( m&Fday (.2 in pre&nancy and lactation and elderly.

SourcesE&& yol4, sh, mil4, meat, %heat, corn, cabba&e, roots and tubers. !ich sources

are yeast, rice polishin&, %heat &erms, cereals, le&umes 7pulses9, oil seeds, e&&,

mil4, meat, sh and &reen leafy ve&etables.

%efciency0

$. Severe deciency of vitamin #/ is uncommon.

(. :eurolo&ical

a. n the early $?2@s, sei0ures %ere observed in infants as a result of severe

vitamin #/ deciency caused by an error in the manufacture of infant

formula. Abnormal electroencephalo&ram 7EE;9 patterns have been

noted in some studies of vitamin #/ deciency.b. 8onvulsions in infants have been attributed to pyridoxine deciency. t is

related to lo%ered activity of ;lutamic acid decarboxylase, for %hich

pyridoxal " is a coen0yme. As a result there occurs lo%erin& of X'amino

butyric acid 7;A#A9 in the brain %hich causes convulsions.

c. ther neurolo&ic symptoms noted in severe vitamin #/ deciency include

irritability, depression, and confusion additional symptoms include

inPammation of the ton&ue, sores or ulcers of the mouth, and ulcers of

the s4in at the corners of the mouth.

1. Jypo chromic microcytic anemia.

*. Deciency state is indic

Documents

13 .Vitamins Docx.copy Docx