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Vitamins:

1. Explain the role of ascorbic acid in post translational modication. Pon May

2007

a. The biosynthesis of a protein or a polypeptide in a living cell is referred to as

translation. The proteins synthesized in translation are, as such, not functional.Many changes take place in the polypeptides after the initiation of their synthesis

or, after the protein synthesis is completed. These modications include protein

folding, trimming by proteolytic degradation, intein splicing and covalent changes

which are collectively known as modications. Covalent modications include

phosphorylation, hydroylation and glycosylation.b. !it C plays a role in posttranslational hydroylation of proline and lysinec. "ydroylation # $uring the formation of collagen, the amino acids proline and lysine

are respectively converted to hydroyproline and hydroylysine. This hydroylation

occurs in the endoplasmic reticulum and re%uires vitamin C.2. F!"#E #$"P:

1. &n vitamin '1( deciency, increased folate levels are observed in plasma. The activity

of the enzyme homocysteine methyltransferase is low in '1( deciency. )s a result,the only ma*or pathway for the conversion of +-methyl T" to tetrahydrofolate is

blocked and body T" pool is reduced. /ssentially almost the entire body folate

becomes trapped as +-methyl T". This is known as folate trap or methyl frap.

(. ln this manner, '1( deciency results in decreased folate coenzymes that leads to

reduced nucleotide and $+) synthesis. )lthough the tissue folate levels are ade%uate

or high, there is a functional folate deciency due to the lack of T" pool. The outcome

is the development of megaloblastic anemia.

0. )dministration of the amino acid methionine has been shown to partially correct the

symptoms of '1( deciencies. This is due to the fact that the formation of +-methyl

T" is inhibited by -adenosylmethionine. ) combined therapy of vitamin '1( and

folic acid is generally employed to treat the patients with megaloblastic anemia.%. &chillin'(s test#

1. The test is for assessing weather '1( absorption from the gut is normal. &t is done in

two stages.

(. tage &# 2adioactive labelled 3Cobalt-456 vitamin '1(, one microgram is given orally.

imultaneously an intramuscular in*ection of unlabeled vitamin '1( is given to

saturate tissues with normal vitamin '1( and radioactive vitamin '1( will not bind to

body tissues. Therefore, the entire absorbed radioactivity will pass into the urine. The

patient7s urine is then collected over the net (8 hours to assess the absorption.

0. &n patients with pernicious anemia or with deciency due to impaired absorption, less

than 9 of the radioactivity is detected in urine.

8. tage &&# &f an abnormality is found, the test is repeated, with radioactive vitamin plusintrinsic factor given orally, and urine is collected for (8 hours. &n pernicious anemia,

there is lack of intrinsic factor, so that the rst test is abnormal: but the second test is

normal.

). #he ele*ated excretion of formimino 'l+tamate ,F-!/ occ+rs in hich

condition i*e the reaction bloc3ed. Pon 4o* 2005

)ns# &n the metabolism of the amino acid histidine there is folic acid dependent step at the

point where formimino-glutamic acid 3;iglu<6 is converted to glutamic acid. &n folic acid

decient patients, this reaction cannot be carried out, as a result, ;glu< accumulates in

the blood and ecreted in urine. iglu ecretion in urine is an inde of folic acid deciency.

=hen a ;loading dose< of histidine is given, the ecretion of >iglu7 in urine is increasedfurther 3"istidine loading test6.



(

6. hy does the dietary re8+irement of pyridoxin increase ith hi'h protein diet

Pon May 2010a. ?yridoine acts in many reactions of amino acid metabolism. ynthesis of certain

specialized products such as serotonin, histamine @ niacin.b. There is evidence that re%uirement of !itamin '4 is increased due to increased

dietary protein intake, as it is involved as coenzyme in many metabolic reactions of

amino acid metabolism.c. ?yridoal phosphate participates in reactions like transamination, decarboylation,

deamination, transsulfuration @ condensation reactions of aminoacids.d. #ransamination#

i. /g. transaminase converts aminoacids to keto acids with ??A acting as

coenzyme. The keto acids enter the citric acid cycle and get oidized togenerate energy.

)lanine B )lpha keto glutarate ?yruvate B Dlutamic acid 3/nzyme )lanine

transaminase6.

e. 9ecarboxylation: eamples#i. Tryptophan is rst converted to -hydroy tryptophan and then

decarboylated to serotonin in the presence of ?A?.ii. "istidine is converted to histamine in the presence of ?A?.iii. Dlutamate is converted to Dama amino butyric acid by similar

decarboylase reaction with ?A?.iv. Catecholamines are synthesized from tyrosine by decarboylase and ?A?.

f. &+lf+r ontainin' "mino "cids , Transulfuration6#

i. ?A? plays an important role in methionine and cysteine metabolism#ii. "omocysteine B erine Cystathionine. 3/nzyme Cystathionine synthase6iii. Cystathionine "omoserine B Cysteine 3/nzyme Cystathionase6

g. -n heme synthesis: ?A? is re%uired for the condensation of succinyl Co) and

glycine to form delta amino levulinic acid 3)A)6. &n '4 deciency, anemia may be

seen.h. -n deamination reactions

i. $ehydratase enzyme converts serine to pyruvate in the presence of ?A?.ii. ?yridoal phosphate is re%uired for the synthesis of niacin from

tryptophan i.e: Coenzyme for kynureninase. This is instance in which one

vitamin synthesizes another vitamin.iii. "ydroymethyltransferase converts serine to a-ketoglutarate with ?A?.

i. Ether important functions of ?A?#i. ynthesis of sphingolipid and myelin formation.ii. )bsorption of amino acid from intestinesiii. ormation of Coenzyme )iv. 'oosting immune functionsv. ?reventing urinary stone formation

*i. Ftilization of unsaturated fatty acids.

5. hich en;yme in $< is meas+red in thiamine deciency 4ame the other

en;ymes that re8+ire thiamine for their acti*ity. Pon 9ec 2002

1. &n thiamine deciency, blood thiamine is reduced, but pyruvate, alpha ketoglutarate

and lactate are increased.

(. #rans3etolase# The second group of enzymes that use T?? as co-enzyme are thetransketolases, in the heose monophosphate shunt pathway of glucose.



0

0. Erythrocyte trans3etolase activity is reduced with accumulation of pentose sugars:

this is the earliest manifestation seen even before clinical disturbances. Measurement

of 2'C transketolase activity is a reliable diagnostic test to assess thiamine deciency.

G. <eriberi:

1. This is a severe thiamine-deciency syndrome found in areas where polished rice is the

ma*or component of the diet. &t is characterised by the following manifestations#

(. C!#

a. These include palpitation, dyspnoea, cardiac hypertrophy and dilatation, which

may progress to congestive cardiac failure.

0. +eurological manifestations#

a. These are predominantly those of ascending, symmetrical, peripheralpolyneuritis.

b. ?olyneuritis common in chronic alcoholics. )lcohol utilization needs large doses

of thiamine. )lcohol inhibits intestinal absorption of thiamine, leading to

thiamine deciency. ?olyneuritis may also be associated with pregnancy and old

age. Thiamine deciency may cause impairment of conversion of pyruvate to

acetyl Co). This results in increased plasma concentration of pyruvate and

lactate, leading to lactic acidosis.

c. =ernicke7s encephalopathy# This is seen primarily in association with chronic

alcoholism and is due to dietary insuHciency or impaired intestinal absorption

of the vitamin. &t is characterized by ophthalmoplegia, nystagmus, cerebellar

ataia.

d. ome alcoholics develop =ernicke- IorsakoJ psychosis syndrom characterized

by apathy, loss of memory, ataia, and a rhythmic to-and-fro motion of the

eyeballs 3nystagmus6.

e. The neurologic conse%uences of =ernickeKs syndrome are treatable with

thiamine supplementation.

8. D& symptoms#

a. )mongst these, anoreia is an early symptom. There may be gastric atony, with

diminished gastric motility and nausea: fever and vomiting occur in advanced

stages.

. $ry beriberi# =hen it is not associated with oedema.

4. =et beriberi# Eedema is associated. &t is probably in part to congestive cardiac failure

and in part to protein malnutrition 3Aow plasma albumin6.

G. &nfantile beriberi# &t occurs in infants born to mothers suJering from thiamine

deciency. igns of infantile beriberi include restlessness and sleeplessness

tachycardia, vomiting, convulsions, and, if not treated, death.

=. 4E>"$<4 ME#"<!-&M

1. Ene-carbon 31C6 groups play a pivotal role in donating carbon atoms for synthesis of

diJerent types of compounds.

(. Ene carbon groups are#

a. ormyl group

b. ormimino group

c. Methanyl group

d. "ydroymethyl groupe. Mrthylene group

f. Methyl group



8

0. /cept mehyl group others are carried by tetrahydrofolic acid. They are contributed by

by amino ac-ids

8. Co( is also a one carbon unit as it participates in carboylation but not accepted by

many as a one arbon unit.

Formation of one carbon +nits:

1. The formate released from glycine and tryptophan metabolism combines with T"

to form +15- formyl T".(. "istidine contributes formimino fragment to produce +-formimino T"

0. =hen serine is converted into glycine +-+15 methylene T" is formed.

8. Choline and betain contribute to the formation of +-methyl T". Choline and

betaine are donors of hydroy methyl groups. )s serine is converted to choline, 0

one-carbon units are used up. $uring the conversion of choline to glycine, these

methyl groups are recovered. "ence, this pathway is called the Lsalvage pathwayL

for one-carbon units.

/tili;ation of one carbon moiety:

Ene carbon units are used to synthesise the following compounds#

1. C( of purine

(. ormylation of Methionyl t 2+)0. C of purine

8. Dlycine

. ?yrimidine nucleotide

$ole of methionine and <12:

1. )ctive methionine is a methyl donor: after release of methyl group it becomes

homocysteine. 2econversion of homocysteine to methionine using +-methyl

T" is a reaction which is catalyzed by a '1(-containing methyltransferase

(. '1( coenzyme accepts methyl group from methyl T") to form methyl

cobalamin. &n '1( deciency this transfer cannot occur and hence T") 3olic

acid6 cannot be regenerated. o folic acid deciency coeists with '1(

deciency a condition called folate trap.0. Most of the one carbon moities are metabolically ;interconvertible< and

catalysed by an +)$?-dependant hydroymethyl dehydrogenases

?. &ymptoms of Vit.@ deciency are met ith more d+e to li*er dysf+nction than

d+e to lac3 of the *itamin. Explain hy this is so. Pon apr 2002

1. Causes for $eciency of !itamin I a. &n normal adults dietary deciency seldom occurs since the intestinal bacterial

synthesis is suHcient to meet the needs of the body. "owever deciency can

occur in conditions of malabsorption of lipids. This can result from obstructive

*aundice, chronic pancreatitis, sprue, etc.b. ?rolonged antibiotic therapy and gastrointestinal infections with diarrhoea will

destroy the bacterial Nora and can also lead to vitamin I deciency.

10. Ao many m' of tryptophan are re8+ired to form 1 m' of niacin Pon May

200?



a. +)$ can also be synthesized from the dietary amino acid tryptophan via the

kynurenine pathway. Tryptophan produces %uinolinate which then forms nicotinate

mononucleotide and, ultimately, +)$B and +)$?B.b. 45 mg of tryptophan would yield 1 mg of +iacin.

Minerals

1. 4ame the en;yme in heme biosynthetic pathay that re8+ire Binc. hich metal

can inhibit this en;yme Pon May 2007

a. ?orphyrin synthesis occurs by condensation of four molecules of porphobilinogenb. Two molecules of 4-aminolevulinate condense to form porphobilinogen 3?'D6 in the

cytosol.c. This reaction is catalysed by a On-containing enzyme )A) dehydralase. lt is

sensitive to inhibition by heavy metals such as lead.

(. an copper deciency c+ase anemia Ao Pon "pril 2002

a. Copper is necessary for iron absorption because Ceruloplasmin3 a copper

containing protein6 promotes iron absorption.

b. Ceruloplasmin is necessary for the incorporation of iron into transferrin.Ceruloplasmin serves as ferroidase and is involved in the conversion of iron from

e(B to e0B in which form iron 3transferrin6 is transported in plasma.c. Copper is also necessary for the synthesis of hemoglobin as Cu, a constituent of

)A) synthase, is needed for heme synthesis.d. Copper deciency produces microcytic hypochromic anaemia, due to impairment of

erythropoiesis and decreases in erythrocyte survival time, which cannot be

corrected by administration of iron.

0. $ole of seleni+m in the body Pon May 200?C Mention the seleni+m re8+irin'

en;ymes in the body. Pon May 201%

1. elenium intake depends on the nature of the soil in which food crops are grown.

2e%uirement is 5-155 microgramPday. +ormal serum level is 5-155 microgramPdl.(. 'iochemical functions#a. elenium containing enzymes#a. Dlutathione peroidase 3D?6 is the important selenium containing enzyme.

2'C contains good %uantity of glutathione peroidase. This enzyme protects

the cells against the damage caused by "(E(b. Thyroin is converted to T0 by K-de-iodinase, which is a selenium

containing enzyme. &n e deciency, this enzyme becomes less active,

leading to hypothyroidism.b. elenium concentration in testis is the highest in adult tissue. &t is necessary

for normal development of spermatozoa. &t is concentrated in the mid-piece

of spermatozoa as a specic seleno-protein in mitochondria.

c. e is involved in maintaining structural integrity of biological membranesd. e prevents lipid peroidation and protects the cells against the free

radicals, including superoide.e. e binds with certain heavy metals 3"g, Cd6 and protects the body from

their toic eJects.f. elenium acts as a nonspecic intracellular anti-oidant. This action of e is

complementary to vitamin /. )vailability of vitamin / reduces the selenium

re%uirement. &n e deciency, tissue vitamin / content is depleted.

elenium, along with vitamin /, prevents the development of hepatic

necrosis and muscular dystrophy0. The FD) codon is acting as the codon for direct insertion of seleno-cysteine into

selenium containing enzymes. eleno-cysteine is directly incorporated into the

protein during biosynthesis. o, seleno-cysteine may be considered as the (1stamino acid.

8. $eciency states#

http://lpi.oregonstate.edu/infocenter/glossary.html





4

a. &n Ieshan province in China, the soil is decient in selenium. This leads to

prevalence of Ieshan disease. &t is characterized by multifocal myocardial

necrosis, cardiac arrhythmias and cardiac enlargement. elenium is known

to cure the disease.b. &solated selenium deciency in other parts of the world caused liver

necrosis, cirrhosis, cardiomyopathy and muscular dystrophy. elenium

toicity is called selenosis.. Toicity#

a. elenium is present in metal polishes and anti-rust compounds. The toicity

symptoms include hair loss, falling of nails, diarrhea, weight loss, and

garlicky odor in breath. The last mentioned symptom is due to the presence

of dimethyl selenide in epired air.b. Iaschinbeck disease is characterized by degenerative osteoarthrosis.

1. 4+tritionD2. -nstr+mentation techni8+es +sed in biochemistryD%. #hyroidD adrenocortical and renal f+nction testsD). -nterpretation of laboratory dataD6. enobioticsD



G

5. En*ironmental ha;ardsD7. ancer biolo'y

&ection --

1. Metabolism of proteinsD amino acidsD2. Aemo'lobin

%. 4+cleotidesD p+rines and pyrimidinesD their re'+lation and associated inbornerrors

). Porphyrias6. A+man 'enetics5. Molec+lar biolo'y7. imm+nolo'y

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