8. protein metabolism

8/21/2019 8. Protein Metabolism

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AMINO ACID METABOLISM

Digestion of proteins: Proteolytic enzymes are secreted as inactive zymogens which are

converted to their active form in the intestinal lumen. This would prevent auto digestion

of the secretory acini. The digestion of protein is eected y enzymes in:

!. "tomach

#. Pancreas and$. %ntestinal cells

&astric:

a. &astric '$( ma)es the food acidic and also denatures proteins. %n infants rennin coverts casein in mil) protein into paracasein for further

digestionc. $hief cells in gastric mucosa secrete pepsinogen which is converted to pepsin

y gastric '$(.d. Pepsin rea)s down proteins into proteoses and peptones.

Pancreas:

a. #ile provides al)aline p'. $holecysto)inin and pancreozymin stimulate pancreatic *uice

c. !ction of pancreatic *uice:i. Trypsinogen is activated y entero)inase to trypsin which in turn

activate other enzymes + Premature activation of trypsin may lead to

acute pancreatitisii. $hymotrypsin is activated y trypsin to chymotripsiniii. Procaro,y peptidase is activated y trypsin to caro,y peptidaseiv. Trypsin- chymotripsin and caro,y peptidase digest protein into

smaller peptides

%ntestinal *uice succus entericus/

a. $ontain amino peptidase- di peptidase and tri peptidase. They ring aout complete digestion into amino acids.

Absorption of amino acids:

a. !sorption occurs in small intestine as an !TP dependant transport process.. Transport is y 5 dierent carriers:

i. 0eutral amino acidsii. #asic amino acidsiii. %mino acids and glycineiv. !cidic amino acidsv. #eta amino acids

c. The asorption of neutral amino acids is eected y &amma&lutamyl cycle+

glutathione reacts with amino acid to form gamma glutamyl amino acid which

is cleaved again to release amino acid across the memrane using 2

molecules of !TP

Clinical applications:

a. 3ndigested protein may enter circulation in some people to produce food

allergy in adults and cow mil) protein allergy in infants. 4.g. of defects in amino acid transport:

i. 'artnup diseaseii. $ystinuria etc

c. %n protein loosing enteropathy there is a huge loss of proteins through &%T

Intracellular digestion:

a. Proteins can e ta)en up y endocytosis and are fused with lysosomes. They are ro)en down y enzymes )nown as cathepsinsc. %t can also occur y attachment to uiuitin and digested y proteosomes

!mino acid metaolism in fasting:

a. 6uscle releases alanine and glutamine

. !lanine is ta)en up y liverc. &lutamine is ta)en y )idneysd. (iver removes amino group and uses the caron s)eleton for

&luconeogenesis


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e. #rain uses ranched chain amino acids for energy

%n fed state:

a. 6uscles and rain ta)e up ranched chain amino acids and release glutamine

and alanine. &lutamine is ta)en y )idney for acid ase regulationc. !lanine is ta)en up y liver

AMMONIA O!MATION"uestions:

#$ %o& is ammonia produced' %o& is it deto(i)ed' *i+e t&o causes and

e,ects of -.perammonemia$ April /0001 Oct /000/$ 2-. ammonia is to(ic to t-e bod.' 2-at are t-e &a.s in &-ic-

Ammonia is produced in t-e bod.' Add a note on -.perammonemia

conditions$ August /0034$ 2rite in detail about -o& ammonia is formed from amino acids5

transported and connected to urea$ eb /006

Introduction:

1. Ammonia is a compound with the formula 0'2. There is no storage form of

amino acids as in the case of carohydrates glycogen/ and lipids

triacylglycerol/.. The e,cess inta)e of amino acids are metaolized to provide energy or converted

to glucose or fat. The amino groups are lost as urea and e,creted2. The presence of 9 amino group )eeps amino acids safely loc)ed away from

o,idative rea)down. emoving the 9 amino group is essential for producing

energy from any amino acid- and is an oligatory step in the cataolism of all

amino acids. ;nce removed- this nitrogen can e incorporated into other

compounds or e,creted- with the caron s)eletons eing metaolized> g of free amino acids which represent the amino acid

pool of the ody. The pool e,ists in several compartments. &lutamate and

glutamine together constitute aout 5>?- and essential amino acids aout 1>?.. The concentration of intracellular amino acids is always higher than the

e,tracellular amino acids. !mino acids enter the cells against a concentration

gradient y active transport.2. !mino acid pool is contriuted y:

a. Turnover of ody protein-. %nta)e of dietary protein andc. The synthesis of nonessential amino acids

&lutamic acid &lutamineDeamination!minosugars !mmonia pool

!sparaginePyrimidinePutrefaction&lutamine@asparagine 3rea

7AT%2A8S O AMMONIA O!MATION

Transamination:

1. The transfer of an amino 0'/ group from an amino acid to a )eto acid is

)nown as transamination. This process involves the interconversion of a pair ofamino acids and a pair of )eto acids- catalysed y a group of enzymes called

transaminases recently- aminotransferase/.

http://en.wikipedia.org/wiki/Chemical_compoundhttp://en.wikipedia.org/wiki/Chemical_compoundhttp://en.wikipedia.org/wiki/Chemical_formulahttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Chemical_formulahttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Chemical_compound


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. Transaminases reuire pyrido,al phosphate P(P/- a coenzyme derived from

vitamin #A.2. Transamination reactions tend to channel amino groups on to glutamate.

&lutamate is the


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. (amino acid o,idase acts on amino acid to form ammonia and )etoacid

8. Damino acid o,idase o,idises glycine to release ammonia

7. 6ono amine o,idase can o,idise monoamines to give ammonia

DETO>IICATION? DIS7OSAL O AMMONIA

Trapping and transport of ammonia:

1. !mmonia is constantly eing lierated in the metaolism of amino acids andother nitrogenous compounds. !t the physiological p'- ammonia e,ists as

ammonium 0'


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To,icity !ssociated with !mmonia

1. !mmonia is neuroto,ic. 6ar)ed rain damage is seen in cases of hepatic and

renal failure.

. !mmonia crosses the rain lood arrier and in the rain it is converted to

glutamate via glutamate dehydrogenase- depleting the rain of 9F&. !s the 9F& is depleted- o,aloacetate falls correspondingly- and ultimately T$! cycle

activity comes to a halt.

2. %n the asence of aeroic o,idative phosphorylation and T$! cycle activity-

irreparale cell damage and neural cell death ensue.


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$aramoyl phosphate synthase1

Ammonia 9 CO/9 / AT7 ;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;; carbamo.l

p-osp-ate9 / AD7 97i

. The caramoyl group is transferred to the 0' group of ;rnithine y ornithine

transcaramoylasae ;T$/ to form $itrulline.

;rnithine transcaramoylasae

Carbamo.l p-osp-ate 9 Ornit-ine;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;; Citrulline

urt-er steps occur in c.toplasm:

2. ;ne molecule of aspartic acid is added to $itrulline to form arginosuccinate

which contain c from dierent sources. !TPs are utilised and catalysed y

arginosuccinate synthetase.

!rginosuccinate synthetase

Citrulline 9 Aspartic acid 9 / AT7 ;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;

Arginosuccinate 9 AM79pi9%/O


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. The production of fumarate in urea cycle is the most important integrating point

with T$! cycle. Kumarate is converted to malate and then to o,aloacetate in T$!

cycle. ;,aloacetate undergoes transamination to produce aspartate which enters

urea cycle. 'ere- it comines with citrulline to produce arginosuccinate.2. ;,aloacetate is an important metaolite which can comine with acetyl $o! to

form citrate and get =nally o,idized.


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'yper

ornithinemia

;rnithine transporter

protein

%ncreased ammonia and ornithine+

$itrulinemia !rginosuccinate

synthetase

%ncreased lood level of arginisuccinate

'yperargininemi

a

!rginase %ncreased arginine in lood

!rgininosuccinic

aciduria

!rgininosuccinate

lyase

!rgininosuccinate in lood and urine.

Kriale rittle tufted hair Trichorrhe,is

nodosa/.

Signi)cance of urea c.cle:

1. 3rea cycle is connected with vital metaolic reactions in the ody.

. %t is integrated with citric acid cycle- which serves as a source of aspartate.

2. Kumarate derived from argino succinate is again integrated with citric acid cycle.

fold or

greater in the concentration of cycle enzymes are oserved. Ihen dietary

proteins increase signi=cantly- enzyme concentrations rise. ;n return to a

alanced diet- enzyme levels decline.

A. 3nder conditions of starvation- enzyme levels rise as proteins are degraded and

amino acid caron s)eletons are used to provide energy- thus increasing the

uantity of nitrogen that must e e,creted.

%87E!AMMONEMIA

#$ %ncreased entry of ammonia to the rain is a primary cause of neurological

disorders associated with hyperammonemia.

/$ 4,amples:

a$ $ongenital de=ciencies of urea cycle enzymes-

b$ 'epatic encephalopathy eye syndrome- several other metaolic

disorders- and some to,ic encephalopathies.

2. $ongenital 4nzyme defects in urea cycle

1. 0 acetylglutamate synthetase 0!&"/ de=ciency 'yperammonemia type %/:

De=ciency of this enzyme results in lac) of 0 acetylglutamate- which is an

activator of caramoyl phosphate synthetase. 6ode of inheritance is autosomal

recessive.

. $aramoyl phosphate synthetase % $P" %/ de=ciency: This defect is inherited in

an autosomal recessive pattern. %n the presence of 0 acetylglutamate-ammonium ions comine with icaronate to form caramoyl phosphate.

'yperammonemia develops as early as the =rst day of life. ! ma*ority of aected

infants die in the neonatal period.


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2. ;rnithine transcaramoylase ;T$/ de=ciency: %n the asence of the enzyme-

accumulated caramoyl phosphate enters the cytosol and participates in

pyrimidine synthesis in the presence of $P" %%. This is the most common urea

cycle defect- with an estimated incidence of 1 case in 1>> persons. %t is

transmitted as an lin)ed trait.


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2. Iilson disease


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formyl T'K.. 'istidine contriutes formimino fragment to produce 05formimino T'K2. Ihen serine is converted into glycine 0501> methylene T'K is formed. !s

serine is converted to choline- 2 onecaron units are used up. During the

conversion of choline to glycine- these methyl groups are recovere. 'ence-

this pathway is called the salvage pathway for onecaron units.


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#$ Introduction:a$ *l.cine is the organic compound with the formula 0'$'$;;'. %t is the

smallest of the > amino acids commonly found in proteins. $ollagen

contains aout 25? glycine. %n its crystallized form glycine is a freeHowing-

sweettasting crystalline material. %t is a non essential and glucogenic amino

acid.. &lycine is actively involved in the synthesis of many specialized products li)e

heme- purines- creatine etc. in the ody.c. %t is incorporated into proteins U used in the synthesis of serine and glucosed. %t participates in onecaron metaolism.

/$ Bios.nt-esis:1. %t is iosynthesized in the ody from the amino acid serine. The enzyme

"erine hydro,ymethyltransferase catalyses this transformation y removing

one caron atomSerine 9 tetra-.drofolate *l.cine 9 N35N#0;Met-.lene

tetra-.drofolate 9 %/O. &lycine synthesis is also eected y glycine synthase from $;- 0'< and one

caron unit .CO/ 9 N%J9 9 N35N#0;Met-.lene tetra-.drofolate 9 NAD% 9 %9 =

*l.cine 9 tetra-.drofolate 9 NAD9

2. &lycine is also synthesised from threonine y threonine aldolase.

T-reonine *l.cine 9 Acetalde-.de$


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Argenine 9*l.cine ;;;;;;;;;;;;;;;;;;;;;;;;*uanido acetic acid9

Ornit-ine

. &uanido acetic acid is methylated to "adenosine methionine "!6/

y methyl transferase to form creatinine. This reaction occurs in liver.

6ethyl Transferase

*uanido acetic acid 9 S;adenos.l met-ionine ;;;;;;;;;;;;;;;;;;;;

Creatine 9 S;adenos.l -omoc.steine2. $reatine is phosphorylated to creatine phosphate y creatine )inase

$reatine )inase

Creatine 9 AT7 ;;;;;;;;;;;;;;;;;;;; Creatine p-osp-ate9 AD7 The reverse of this reaction yields energy for muscle contraction and

is called Lo-manns reaction. to 1.< mg@dl. "erum creatine level is >. to >.< mg@dl

2. 3rine contains negligile amount of creatine ut increased in musculardystrophies


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o,alate+ this is then e,creted in the urine. This leads to nephrocalcinosis and

the eventual development of endstage renal failure. 6anagement:#$ %ncrease inta)e of water/$ educe dietary inta)e of o,alate y minimizing the inta)e of leafy

vegetales- tea- spinach etc.


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J$ Metabolicall. important products formed from met-ionine$ Oct /0043$ Transmet-.lationH No+ember #J1 April /00#G$ Acti+e met-ionine$ April #6F$ Metabolic role of met-ionine;April /00#

MET%IONINE

Introduction:

1. The sulphur containing amino acids are met-ionine5 c.steine and c.stine.. !mong these- only methionine is essential. %t is a sulphur containing- essential-

and glucogenic amino acid.2. 6etaolism is divided into 2 parts:

a. !ctivation and Transmethylation reactions. $onversion to $ysteine and cysteinec. Degradation and conversion of $ysteine into various products

Steps:1. Acti+ation of Met-ionine: 6ethionine is activated to "adenosyl methionine "!6/

y transferring the adenosyl group to sulphur atom

6ethionine sadenosyl transferase

Met-ionine 9 AT7QQQQQQQP S;adenos.l met-ionine 9 77i97i

. Met-.l transfer or transmet-.lation: Krom "adenosyl methionine the methylgroup is transferred to a methyl acceptor and gets converted to "adenosyl

homocysteine. %n "!6- due to the presence of a high energy ond- the methyl group

is laile- and may e transferred easily to other acceptors.

6ethyl transferase

S;adenos.l met-ionine 9 Met-.l acceptor QQQQP S;adenos.l -omoc.steine2. ormation of %omoc.steine: !denosyl group is removed from to form

homocysteine. Thus- 6ethionine is also the source of homocysteineQa metaolite

associated with atherosclerotic vascular disease.!denosine homocysteinase

S;adenos.l -omc.steine QQQQQQP %omoc.steine9 Adenosine


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iv. 'omocysteine is also involved in the aggregation of (D( particles. !ll

this leads to an increased tendency for atherogenesis- and

conseuently heart complications.v. "upplementation of diet with folic acid- vitamin #1 and vitamin #A

have some ene=cial eects in lowering plasma homocysteine levels.. %omoc.stinurias:

i. 'omocystinurias are a group of metaolic disorders characterized y

the accumulation and increased urinary e,cretion of homocysteine

and "adenosyl methionine. Plasma concentration of methionine is

increased.ii. 'omocystinuria type % is due to a defect in the enzyme cystathionine

synthase. !ccumulation of homocystetne results in thromosis-

osteoporosis and mental retardation. Kurther- the de=ciency of

cystathionine is associated with damage to endothelial cells which

might lead to atherosclerosis.iii. The other homocystinurias are associated with enzyme defects in the

conversion of homocysteine to methionine y remethylation.iv. 'omocystinuria ll : 0501> methylene T'K reductase.

v. 'omocystinuria lll : 05

01>

methylene T'K homocysteinemethyltransferase. This is mostly due to impairment in the synthesis

of methylcoalamin.vi. 'omocystinurla lR: 05 6ethyl T'K homocysteine methyl transferase.

This is primarily due to a defect in the intestinal asorption of vitamin

#1.2. $yanidenitroprusside test:

i. %t is a screening test. 5 ml urine saturated with sodium chloride- <

drops of ammoniacal silver nitrate. !fter 1 min- F$0 potassium

cyanide/ is added drop y drop until solution is clear. Then < drops of

freshly prepared sodium nitroprusside is added.ii. ! magentared colour appearing within 2 min and persisting for at

least 2 min is indicative of the presence of

homocystine@homocysteine in urine. "peci=c amino aciduria may e

con=rmed y chromatography.

T!ANSMET%8LATION !EACTION+ ACTIRE MET%IONINE "hort notes/

1. The transfer of methyl group ch2/ from one active methionine to an acceptor is

called transmethylation.. Acti+e met-ionine:

a. 6ethionine reacts with !TP forming " adenosylmethionine "!6/ which is

called active methionine.. 6ethionine has to e activated to "adenosyl methionine "!6/ to donate the

methyl group.c. The synthesis of " adenosyl methionine occurs y transfer of an adenosyl

group from !TP to sulphur atom of methionine and the sulphur atom ecomes

sulfonium atom and is catalysed y methionine sS adenosyl transferase. "!6

is a sulfonium compound. This reaction is also unusual since all the three

phosphates of !TP are eliminateda s pyrophosphates PPi/ and inorganic

phosphates Pi/. Three high energy phosphates 2 !Tn arc consumed in the

formation of "!6.6ethionine sadenosyl transferase

Met-ionine 9 AT7QQQQQQQP S;adenos.l met-ionine 9 77i97i4$ unctions of S; adenos.l met-ionine Kacti+e met-ionine

a. "adenosyl methionine is highly active due to its positive charge.

. "!6 is the main source of methyl groups in the ody. The enzymes involvedin the transfer of methyl group are collectively )nown as 6ethyl Transferase.c. Krom "adenosyl methionine the methyl group is transferred to a methyl

acceptor and gets converted to "adenosyl homocysteine 6ethyl transferase


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S;adenos.l met-ionine 9 Met-.l acceptor QQQQP S;adenos.l -omoc.steined. %n this reaction methionine is regenerated y converting homocysteine to

methionine y remethylation.e. "!denosylmethionine is also involved in the synthesis of polyamines

spermidine- spermine/.


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a. The enzyme cysteine dio,ygenase o,idizes cysteine to cysteine sul=nate

which- on further o,idation- is converted to cysteic acid. The latter

undergoes decaro,ylation to produce taurine which con*ugates with ile

acids.. $ysteic acid can also e degraded to pyruvate- which is glycogenic.


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*L@TAT%IONE

1. &lutathione is gamma glutamyl cysteinyl glycine. &lutathione is generally

areviated as &"'- to indicate the reactive "' group. &lutathione areviated

&"'/ is a tripeptide composed of glutamate- cysteine and glycine that has numerous

important functions within cells.

/$ *lutat-ione s.nt-esis: &lutathione is formed y glutamic acid- $ysteine andglycine. #oth steps need hydrolysis of one !TP each.

G&lutamyl synthase*lutamate9C.steine9AT7;;;;;;;;;;;;;;;;;;;;*lutam.lc.steine9AD797i

&lutathione synthase;*lutam.lc.steine9*l.cine9AT7;;;;;;;;;;;;;;;;;;;;;;;;;;;;; *lutat-ione

4$ !ole of *lutat-ione:1. &lutathione is involved in amino acid transport across cell memranes the G

glutamyl cycle/ %t reacts with the amino acid to form gamma glutamyl amino

acid. This is catalyzed y gamma glutamyl transferase. The glutamyl amino

acid is then cleaved to give the free amino acid. The net result is the transfer

of an amino acid across the memrane

. $oenzyme ole: 6etaolic role of &"' is mainly in reduction reactions. Thehydrogen released is used for reducing other sustrates. ! few e,amples are

shown elow:i. 6aleyl acetoacetate V fumaryl acetoacetateii. $ysteic acid V taurine

2. #$ 6emrane %ntegrity: &lutathione is present in the #$s. This is used for

inactivation of free radicals formed inside #$. This is called free radical

scavenging. The occurrence of hemolysis in &PD de=ciency is attriuted to

the decreased regeneration of reduced glutathione.


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2. 0!cetylglutamate is an allosteric regulator of caramoyl phosphate synthase l-

the =rst enzyme in urea synthesis.


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cells &lutamine is hydrolyzed to glutamate and ammonia y glutaminase. !mmonia

helps to uer 'E in urine.


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2. Mec-anism of action:a. 0itric o,ide promotes the synthesis of c&6P. lt is elievedt hat some of

the actions of 0; are mediated through c&6P and protein )inase $. in

smooth muscle.. Dephosphorylation of myosin light chain occurs leading to rela,ation of

smooth muscle.J$ 7-.siological actions:

a. 0; functions as a vasodilator and causes rela,ation of smooth

muscles.De=ciency cause hypertension and e,cessive production leads to

hypotension as occurs in septic shoc).. lt is a )ey molecule in the regulation of lood How and the lood pressurec. 0; acts as an inhiitor of platelet aggregation and adhesion.d. lt functions as a messenger molecule of the nervous system

neurotransmitter/.e. 0; mediates the actericidal actions of macrophages.f. %t is involved in the erection of penis.g. %n $0" 0; stimulates releasing hormones li)e $'- &'' etc.

3$ T-erapeutic actions:a. %t is used in treating angina pectoris in the form of nitroprusside and nitroglycerin

which release 0;.. %nhalation of 0; reduces pulmonary hypertension.c$ %t is useful in treating impotence: eg. sildena=l Riagra/

7OL8AMINES

1. Polyamines are putrescine- spermidine and spermine.. They are aliphatic amines.2. They are synthesized from ;rnithine y ornithine decaro,ylase with coenzyme

pyrido,al phosphate.


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Aromatic amino acids are amino acids which include an aromatic indole/ ring.

4,amples include: phenylalanine-tryptophan- and tyrosine+ histidine is also

considered as aromatic amino acid.

T.rosine

Con+ersion of p-en.l alanine to t.rosine:

1. Phenylalanine and tyrosine are structurally related aromatic amino acids.Phenylalanine is an essential amino acid while tyrosine is nonessential. #oth are

glucogenic and )etogenic.. The only function of phenyl alanine is its conversion to tyrosine. %f tyrosine is

supplied adeuately the reuirement of phenyl alanine ecomes minimal. 'ence

tyrosine has sparing action on phenyl alanine.2. Phenyl alanine is converted to tyrosine y phenylalanine hydro,ylase using 0!DP'-

and tetra hydroiopterin as coenzymes. Phenylalanine hydro,ylase is a mi,ed

function o,ygenase. ;ne atom of o,ygen is incorporated into water and the other

into the hydro,yl of tyrosine. The reductant is the tetrahydrofolate related cofactor

tetra-.drobiopterin- which is maintained in the reduced state y the 0!D' de

pendent enzyme dihydroiopterin reductase D'P/.

CATABOLISM O T8!OSINE AND 7%EN8LALANINE

Introduction:

1. Tyrosine is an aromatic amino acid. %t is synthesized from phenylalanine- and so

is a nonessential amino acid. The need for phenylalanine ecomes minimal- if

adeuate tyrosine is supplied in the food.. The metaolism of phenylalanine and tyrosine is considered together2. Degradative pathway of phenylalanine and tyrosine are the same- since

phenylalanine is converted to tyrosine and then metaolized.

"tep 1: 7-en.lalanine to t.rosine: The reaction involves addition of a hydro,yl

group to the aromatic ring- y phenylalanine hydro,ylase. %t needs 0!DP'-

0!D' and tetrahydroiopterine as coenzymes. !s this is an irreversile

reaction- tyrosine cannot replenish phenylalanine. 'ence- phenylalanine is

essential in food. phenylalanine hydro,ylase de=ciency loc)s the conversion

of phenylalanine to tyrosine resulting in the disorder phenyl)etonuria PF3/.

phenylalanine hydro,ylase

Phenyl alanine E ; E tetrahydroiopterin E 0!DP' E 'E QQQQQ

WTyrosineE'; E dihydroiopterin E 0!DP

"tep : Transamination: Degradative pathway of phenylalanine and tyrosine are

the same- since phenylalanine is converted to tyrosine and then metaolized.

Tyrosine is transaminated to give para hydro,y phenyl pyruvic acid y tyrosine

transaminase. %t is pyrido,al phosphate dependent. %t is induced y

glucocorticoids. Tyrosine is transaminated to parahydro,ypyruvic acid y

tyrosine transaminase and pyrido,al phosphate.

Phenylalanine

Phenyl alanine hydro,ylase

Tyrosine

!Fetoglutarate Tyrosine transaminase E P(P

&lutamic acid

Para hydro,y phenyl pyruvic acid

"tep 2: Production of homogentisic acid : Parahydro,yphenylpyruvic acid is

converted to homogentesic acid. The reaction involves parahydro,ypy

pyruvate hydro,ylase- a copper containing enzyme and !scorpic acid.

Parahydro,y phenyl pyruvic acid

; Para hydro,y phenyl pyruvic acid

http://en.wikipedia.org/wiki/Amino_acidshttp://en.wikipedia.org/wiki/Aromaticityhttp://en.wikipedia.org/wiki/Aromaticityhttp://en.wikipedia.org/wiki/Phenylalaninehttp://en.wikipedia.org/wiki/Phenylalaninehttp://en.wikipedia.org/wiki/Tryptophanhttp://en.wikipedia.org/wiki/Tyrosinehttp://en.wikipedia.org/wiki/Amino_acidshttp://en.wikipedia.org/wiki/Aromaticityhttp://en.wikipedia.org/wiki/Phenylalaninehttp://en.wikipedia.org/wiki/Tryptophanhttp://en.wikipedia.org/wiki/Tyrosine


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$; hydro,ylase E !scoric acid

Dihydro,y phenyl acetic acid homohentesic acid/

"tep


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2. (eu)oderma is due to asence of tyrosinase and melanin forming cells.


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the diameter of the colony- is roughly proportional to the amount of

phenylalanine in the serum.

2. erric c-loride test: Phenyl)etones will give a transient lue green

color on adding a drop of ferric chloride to urine sample.. Treatment:

i. 4arly detection y routine 0# screeningii. (ow phenyl alanine diet 4g. Tapioca

/$ ALA7TAN@!IA

1. Al->>> irths.. This is an !utosomal recessive condition that is due to a defect in the enzyme

homogentisate o,idase- which participates in the degradation of tyrosine.2. !s a result- a to,ic tyrosine yproduct called homogentisic acid or al)apton/

accumulates in the lood- and is e,creted in urine in large amounts. %t

lac)ens the urine on standing.->>> irths. 4nzyme tyrosinase is asent2. 'ypo pigmentation of iris- s)in and hairs.


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glucogenic and )etogenic in nature. lt is a precursor for the synthesis of important

compounds- namely 0!DE and 0!DPE coenzymes of niacin/- serotonin and

melatonin./$ Compounds s.nt-esied from tr.ptop-an:

1. !lanine. !cetoacetyl $o!2. Kormyl group1 $ unit/


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!TP!DPEpi

NAD79

Serotonin pat-&a.:

1. "erotonin is produced in the rain- mast cells- platelets and &%T mucosa.

. #iosynthesis:a. Tryptophan is hydro,ylated y tryptophan hydro,ylase with the coenzyme

tetra hydroiopterine.. 5hydro,y tryptophan is decaro,ylated to 5hydro,y tryptamine

serotonin/ y P(P dependant decaro,ylase.

unctions of Serotonin:

c. "erotonin is an important neurotransmitter. The eect of serotonin is

dependent on the amount of serotonin availale at the synaptic site. Part

of the serotonin released is again ta)en up reupta)e/. "elective serotonin

reupta)e inhiitors ""%/ are widely used in the treatment of psychiatric

disorders.d. !fter food rich in carohydrate insulin secretion enhances tryptophan

upta)e and conversion to serotonin e,plaining food induced sleep.e. "erotonin is involved in mood- sleep- appetite and temperature

regulation.

$ataolism:

a. "erotonin is con*ugated to sulphate or glucuronic acid and e,creted in

urine.. 6!; converts serotonin to 5hydro,y indole acetic acid+ '%!!/ hence

6!; inhiitors will cause mood elevation. eserpine increases the

degradation of serotonin- hence acts as a depressant drug. (ysergic acid

diethylamide ("D/ competes with serotonin and- therefore- acts as a

depressant

Carcinoid tumor:c. %t is a cancer arising from small intestine and secretes serotonin in large

uantities.d. Klushing- sweating- diarrhea and hypertension are the symptoms.e. Diagnosed y urinary '%!! and serum serotonin levels which are

elevated.

MELATONIN

1. Pineal gland secretes melatonin and is connected with iological rhythm.. "erotonin is acetylated and then methylated with the help of "adenosyl methionine

to form melatonin.4$ Inborn errors: %A!TN@7 DISEASE:

1. !utosomal recessive.. Tryptophan and other neutral aminoacids are not asored in the small

intestine - and are converted y gut acteria convert to indolic compounds

that are to,ic to the $0".2. enal tuular transport is defective and causes gross aminoaciduria.


29/29

18A

2. %t is responsile for ma,imum uering action.

8. protein metabolism

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