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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.
