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(UreaCycle)

AtifHassanKhirelsied,BSc,MSc,PhD

DepartmentofBiochemistry

InternationalUniversityofAfrica,Khartoum,Sudan

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AnOverviewofAminoAcidsMetabolism

Nonprotein compounds

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TheCentralRoleofTransaminationandOxidative

DeaminationinAminoAcidsMetabolism

Endogenous

synthesis

Body proteins

Transaminases

Urea

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Bodyproteinturnover

1. Bod roteins are in a d namic stead state turnover.

. .

3. Around75%

of

the

liberated

amino

acids

are

reutilized.

4. Excess amino acids are ra idl de raded.

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Bodyproteinturnover

.

degradedinlysosomes byATPindependentprocesses.

2. Intracellular proteinsaredegradedinproteosomes.

Thehalflifetime(t )ofproteinsvaryconsiderably;

Approximately20daysforalbumin.

Someenzymesmayhaveat

ofonlyafewhours.

PESTrichsequences(Pro,Glu,Ser,Thr),targetsomeproteins.

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Theproteosomes

1. Proteosomes are lar e multimolecular rotein

complexescontainingproteases.

2. Ubiquitination servesasasignalfortheactionsof

.

3. Ubiquitin islinkedtolysineresiduesinthetarget

protein

by

a

family

of

(Eligases).

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IntracellularProteinsareSelectivelyTargetedforDegradationby

Ubiquitination

Eligases

Ubiquitinspecific

Theresiduepresentat the

proteinaminoterminalaffects

AminoterminalMetorSer

retar s,w ereas sp or rg

acceleratesubiquitination

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TheAminoAcidsCatabolism

.

humans.

2. Aminoacidscatabolismincreasesduring:

Fasting

or

starvation. Debilitatingdiseases(e.g,DM).

Nutritionaldeficiencies.

3. Thenitrogenbalanceisusedtoassessthebodyprotein

turnover.

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The NitrogenBalance

.

Makingmoreproteinthanbreakingdown.

2. Occursin:

Pregnantwomen

Infantsandchildren

Athletes(building

muscle)

Convalescence

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TheNitrogenBalance

.

Breaking

down

more

protein

than

you

are

making

a a o sm>ana o sm

2. Occursin: SevereIllness

Trauma(fractures,burns,surgery,stressetc.,)

Starvation/anorexia

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The NitrogenBalance

Nitrogenequilibrium.

Protein

made

=protein

broken

down

Anabolism=catabolism

Occursin: Healthynonpregnantadults.

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The NitrogenMetabolism

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Theroleoftransaminases andglutamatedehydrogenase

synthesisand

catabolism.

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Theroleoftransaminases andglutamatedehydrogenase

u ama e e y rogenasearecen ra n

bothamino

acid

synthesis

and

catabolism.

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The AmmoniaMetabolism

Ammoniaistoxicevensmallconc.

(Ammonotelic animals).

Ammoniaiscarriedinthebloodglutamine

In

the

gills,

glutamine

is

hydrolyzed

to

glutamic acid

re easest eammonia.

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The AmmoniaMetabolism

bodiesexcrete

nitrogen

as

uric

acid

(Uricotelic animals).

Verte rate anima s

inc uding

umans

excrete

nitrogen

as

urea(Ureotelic animals).

SmallamountsofNH3 isexcretedintheurineasNH4+

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The TransportofAmmoniaintheBody

Alanine andglutamine areparticularlyimportantvehiclesofammoniatransport

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The TransportofAmmoniaintheBody

Inmosttissues,ammoniaisconvertedglutamineby

glutaminesynthetase.Glutamate+NH Glutamine

Glutamine+H2O Glutamate+NH3

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The GlucoseAlanine Cycle

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The UreaCycle

Ureaisthema orend roductofnitro enmetabolismin

humansandmammals.

Urea

Theoverallureaformationreactionis:

4 + 2+ > rea+ 2 +

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The UreaCycle

Mitochondrion

Cytosol

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The ReactionsoftheUreaCycle

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The EnzymesoftheUreaCycle

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Carbamoyl PhosphateSynthetase1

1. TherearetwoCPs nthetases:

Mitochondrial

CPS

I,

forms

CP

for

urea

cycle

CytosolicCPsynthatase (CPSII),inpyrimidine

.

2. CPSIisallostericallyactivatedbyNacetylglutamate.

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TheSource ofUreaNitrogen

1. The1st amine rou fromoxidativedeamination of

glutamate.

T e2n aminegroup romAsparticacid.

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TheDisordersofUreaCycle

Inheriteddisordersmaycauseapartialblockinureacycle

andresultsinhyperammonemia .

yperammonem a smoreseverew en eme a o c

blockoccursatthefirstreactions.

Acompleteblockofanystepintheureacycleisfatal.

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TheDisordersofUreaCycle

III

V

IV

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Hyperammonemia

damage

and

death.

DepletesTCAcycle

Defectiveneurotransmission

IncreasedGlutaminesynthesis.

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Hyperammonemia

:

Vomiting

avoidanceofhighproteinfoods

intermittentataxia

irritability

lethargy

mentalretardation.