Biochemistry-UNIT 5
Biochemistry-UNIT 5
tV
Cont
ent
Protei
n:aminoacid, hormones
Essenti
alami noaci
ds.Biosynthesisofprotei
ninthe
cell
Roleofnucleicaci
dsi nprot
einsy nthesi
s
Nitr
ogenousconst i
tuentsofurine,blood,t
hei
rori
gin
–ureacycle,uri
cacidformation,gout
Plasmaproteinsandt hei
rfunctions.
PROTEI
NS
Protei
nsar et heimpor t
antandmostabundantcomponent softhebody .
Protei
nsar eessenti
alnut ri
entsforthehumanbody .Itaccount
sf orabout
16% oft otalbodywei ght.Andt hesearethebuil
dingblocksofthebody .
Protei
nscont aincar
bon, hydrogen,oxy
genandnitr
ogen.
Thebasi cunitofproteinsisami noacidsandeachami noacidcontai
nsan
acidi
cgr oupandanami nogroup.About21ami noacidshavebeenf oundin
theproteins.
Ty
pesofami
noaci
ds
Essent
ialami
noacids-Theami noaci
dswhi charenotsy
nthesi
zedin
thebodybutneedtobet akeni
nthediet
.Therear
e10essenti
alamino
aci
dsweneedt ot
akeinthediet
.
Nonessenti
alami
noacids-t
hesear
etheami
noaci
dswhi
chcanbe
sy
nthesi
zedi
nthebody
.
Semiessent
ialaminoacids-Theaminoacidwhichisrequi
redinthedi
et
onl
ydur i
ngpregnant,l
act
ati
ngmot herandforchil
drenforthei
rgrowth
andtheseaminoacidsarenotessent
ialf
ornor
mal adult
s.
Essent
ialami
no nonessent
ialami
no Semiessenti
al
aci
ds aci
ds aminoacids
Hi
sti
dine Al
ani
ne Ar
gini
ne
I
sol
euci
ne Ar
gini
ne Hi
sti
dine
Leuci
ne Aspar
ti
caci
d
l
ysi
ne Cy
sti
ne
Met
hioni
ne Gl
utami
caci
d
Pheny
lal
ani
ne Gl
utami
ne
Thr
eoni
ne Gl
yci
ne
Tr
ypt
ophan Pr
oli
ne
Val
i
ne Ty
rosi
ne
Ser
ine
Cl
assi
fi
cat
ionofpr
otei
ns–
I
.Basedonchemicalcomposi
ti
on–Basedont hechemicalcomposi
ti
onof
t
hepr ot
einst
her
earemainl
y3typesofpr
otei
nstheyare
1.Si
mpleproteins
2.Conj
ugatedpr ot
eins
3.Deri
vedproteins
Si
mplepr
otei
ns-Thesearetheprot
einsmadeupofonl
yami
noaci
dse.
g.-
Pl
asmaal
bumin,col
lagenandker
ati
n
II
.Basedonst r
ucture-Basedont
hest
ruct
ureoft
hepr
otei
ns.Thepr
otei
ns
areclassi
fi
edintotwotypes
1.Globul
arprotei
n
2.Fibr
ousprotein
Globularpr
otei
ns-Gl
obul
arprot
einsar
espheroi
dorov ali
nshape.Allt
he
enzymes are gl
obul
arprotei
ns and t
hese pr
otei
ns per
for
m vari
etyof
funct
ions.
Fibr
ouspr otei
ns-Thesearelongr i
bbonsorf i
bersinshapeandper
for
m
mechanicalandst r
uctur
alfuncti
on.Provi
dessupportt
othecel
laswel
las
thewholeor gani
sm.Thef ibrousprot
einsareextr
emelystr
ongandt
hese
aremainlyinanimalinori
gin.
I
II
.Classificati
onbasedonbi ologicalf
unct
ion
Enzy micpr otei
n
Transpor t/carr
ierprot
ein
Nut r
ientandst orageprotein
Immunepr otei
n
Cont racti
l
eormot orprotei
n
Regul ator
ypr otein
Toxicpr otein
Structuralprotein
Enzymicprotei
n-almostallr eact
ionsarecatal
yzedbyspeci alprot
eins
cal
ledenzymes.Enzymicproteinal
socall
edascat al
yti
cprot
einwhichmay
besimpleorconjugat
ed.E.
g.-amy l
ase,ur
ease,
alkali
nephosphataseet
c.
Transportorcarr
ierpr
otei
n-thesearethepr otei
nswhi
chareinvol
vedin
tr
anspor t
ingofmanyessenti
albi
ologi
calsubstancet
ovari
ouspar
tsofthe
body.
E.g.
-Transfer
ri
ncarr
yir
on,hemoglobi
ncarryoxygen.
Nutr
ientandst or
ageprotein-st
orageprot
einsarebiol
ogicalr
eser
vesof
metalsi
onsandami noacidsusedbyorganisms.E.
g.-
Ferr
iti
nisastor
age
pr
oteinthatst
oresir
on
I
mmunepr oteins-proteinswhichservest
hedefensemechani
sm i nthe
body
E.
g.-
immunogl obuli
nI gG,I gM,IgA,IgD,I
gE ar
et he i
mmune response
prot
einswhichwi l
lprotectsfr
om i
njur
y.
Cont
ract
ilepr
otei
n-thesearethepr
otei
nswhi
cht
akespar
tint
hemuscl
e
cont
ract
ionE.g.
-Act
in,myosi
n
Regulat
oryprotein-
somepr ot
einsregul
atecel
l
ularorphy
siol
ogi
cal
act
ivi
ty.
E.
g.-
insul
inregulatessugarmetaboli
sm
Toxicpr
otei
ns-Somepr
otei
nsact
sasat
oxi
csubst
ancesuchassnake
venom.
Str
uct
uralprot
eins-Pr
otei
nsthatcont
ri
but
eint
hest
ruct
ureoft
het
issues
suchascoll
agenandelast
in
1V.Cl
assi
fi
cat
ionbasedonsour
ceofpr
otei
ns
Animalproteins-thesearethepr
otei
nsderi
vedfrom ani
malsour
ces
suchaseggs, mil
k,meat.
Plantprot
eins-t heseprotei
nsderi
vedfr
om plantsourcessuchas
beans,nut
s, seeds,ri
ceetc.
Speci
ali
zedpr
otei
ns
Pl
asmapr
otei
ns
Pl
asmacontainshundresofdiff
erentprot
einswhichar eamixtur
eof
si
mplepr
otei
ns,gl
ycopr
otei
ns,
li
poprotei
nsandotherconj
ugat
edpr
otei
ns.
Nor
mal
ser
um pr
otei
nlev
eli
s63-
83g/
L
Maj
orpl
asmapr
otei
nsar
eal
bumi
n,gl
obul
i
n,andf
ibr
inogen.
Al
bumin-serum al
buminlevelis3.5-
5g/L.iti
ssolublein water
.Itis
synt
hesi
zedinthel
iver
.Itconsi
stsofsingl
epol
ypeptidechainwit
h610
aminoaci
ds.Iti
sri
chinessenti
alaminoacidsl
ikel
ysine,l
euci
ne,val
i
ne,
pheny
lal
ani
ne,
thr
eoni
ne,
argi
nine,
andhi
sti
dine.
Globuli
n-t
henormalserum globuli
ni s2-
2.5g/Ltherearethreeglobul
ins
call
edα, βandγ.α,
βsy nt
hesizedintheli
vercel
lsand(γ) gammagl obuli
n
synthesi
zedintheret
icul
oendot hel
ialsy
stem.Thegammagl obul
insare
al
socal l
edasimmunoglobul
inandhasant i
bodyactiv
ity
.
Fi
bri
nogen-itisaf ibr
ous prot
ein wi
th 6 poly
pepti
de chainjoi
ned by
di
sul
phidebonds.Thenormalser
um fi
bri
nogenlevel
sis0.
2-0.4/
L
Funct
ionsofpl
asmapr
otei
ns
1.Globul
i
ntransport
sions,hor
monesandlipids-t
hecholest
erol
andphospholi
pidsar
ecarri
edbyli
popr
oteinspresenti
ntheα-
gl
obuli
n
2.Plasma pr otei
ns also tr
ansport sever
almet aland other
substance-alfaglobul
i
nt r
ansportcopper,boundhaemoglobin
andt hyr
oxine,thebetaglobul
intransportnonhemei r
onand
al
bumi ntransportmagnesi
um, cal
cium,somedr ugs.
3.Al
bumi
ntr
anspor
tnut
ri
ent
stov
ari
ouspar
tsoft
hebody
4.Osmoti
cregul
ati
on-ser
um al
bumi
nhel
pst
omai
ntai
nosmot
ic
pr
essur
eofplasma
5.Cat
aly
ticf
unct
ion-enzy
meshel
pinchemi
cal
react
ion
6.Prot
ecti
vefuncti
on-immunoglobul
i
n combi
nes wi
th ant
igen
andremovesthem f
rom t
hebody
7.Bl
ood cl
ott
ing-f
ibri
nogen and pr
othr
ombi
n pr
esenti
n al
pha
gl
obul
i
nhelpsinclot
ti
ngofblood.
Coll
agen
Iti
st hemaj
orstruct
uralpr
otei
nfoundi
nconnect
ivet
issue.I
tist
hemost
abundantpr
otei
ni nthebodymakingupto25-
35%ofwhol ebodypr
otei
n
content.
Iti
sthemajorf
ibrousel
ementoft
issuesl
i
kebone,
teet
h,t
endons,
car
ti
lage
andbloodv
essels.
I
ti s synt
hesi
zed by f
ibr
obl
ast
sint
racel
l
ular
ly as a pr
ecur
sorcal
l
ed
pr
ocoll
agen.
Therear
eabout28typesofcol
lagenidenti
fi
ed.Theyaeseenasel
ongat
ed
fi
bri
l
s,whichar
ever
ystrongandflexi
ble.
El
ast
in
I
ti shighlyel
ast
icproteinfoundi ntheconnect
ivet i
ssuesespeci
allyski
n,
bloodv essel
sandinternalor
gansoft hebodywhichdependonel asti
cit
y.
Sinceiti sanimportantproteinofski n,i
thel
pst heskintost r
etchand
retur
nt oit
sorgi
nalpositi
onafterstr
etching
Ker
ati
n-
Itisat y
peoff i
lamentprotein.Kerati
ni saf i
brusproteinmaki
ngupt he
outerlayerofhumanskinpr ovi
dingstructur
alandpr otecti
vef
unct
ion.I
t
anchorst heepi
thel
i
alcell
sofepi der
mist ogetherandal sotot
hedermis
provi
dingabarri
erfr
om externalenvir
onment .
Iti
sanimportantcomponentofskin,hair
,nail
,andital
soprov
idesstrength
andtoughnesstotongueandhar dpalate.Iti
sf or
medf r
om kerat
inocytes
whichhelpinthef ormati
onofout erlayerofskin.Theyareinsolubl
ei n
waterandarenotattackedbypr
oteolyt
icenzymes.
Cal
ori
cval
ueofpr
otei
ns-1Gr
am ofpr
otei
ngi
ves4ki
l
ocal
ori
esofener
gy.
Recommendeddai
lyal
lowances(RDA)
RDAi st
heamountofnut
ri
entandcal
ori
eint
akeperdayf
ormai
ntenanceof
goodhealt
h.
Group Prot
eing/
day
Man 60
Women 60
Lact
ati
ngmot
her 75
I
nfant
s 2.
5/kgbodywei
ght
chi
l
dren 40
Di
etar
ysour
ces
Ani
mal
sour
ce-Meat
,egg,
cheese,
mil
k,f
ish,
Eggi
sthecompl
etepr
otei
ns.
Pl
antsour
ce-Pulses,
beans,cer
eal
s,nuts,
oilseeds.
Cereal
sandpulsesar ethemainsourcesofdi et
arypr
otei
nbecauset
hey
ar
echeap,easi
l
yav ai
labl
eandconsumedi nbulk.
Funct
ionsofpr
otei
ns
Di
gest
ionandabsor
pti
onofpr
otei
ns
1.Mechani
cal
breaki
ngdownofpr
otei
ninmout
h
2.Di
gest
ionofpr
otei
nsi
nst
omach
3.Di
gest
ionofpr
otei
nsi
nsmal
li
ntest
ine
Digest
ioni
nst omach-di
gest
ionbegi
nsinthestomachbygast
ri
cjui
ces
whichcont
ainenzymepepsin.Lar
gepoly
pept
idebreaksdowni
ntosmal
l
pepti
desbytheact
ionofenzy
mepepsinal
ongwit
hHcl .
Lar
gepol
ypept
ides pepsi
n smal
lpept
ides
I
ninfant-i
ninfant
sandchi
l
dren'
smi
l
kcl
ott
ingenzy
mer
eni
nhy
drol
ysi
sthe
pr
oteinsinst
omach.
Mi
lkpr
otei
n(Casei
n) Reni
n Par
acasei
n
Par
acasei
n+cal
cium i
ons cal
ci
um par
acasei
nat
e
Cal
cium par
acasei
nat
e pepsi
n smal
lpept
ides
An i nt
esti
nal secr
eti
on pr
ovi
des ami
nopept
idase, di
pept
idase and
tr
ipepti
daseenzymes.
Di
pept
ides Di
pept
idase Ami
noaci
ds
Tr
ipept
ides Tr
ipept
idase Ami
noaci
ds
Theendpr oductoftheprot
eindigest
ionisaminoaci
danddi
pept
ides,
tr
ipept
ideswhi
chareabsor
bedbyintest
inal
vil
l
us
St
orageandmet
abol
ism ofpr
otei
n
Protei
ns thatare metaboli
zed ar
e broken int
o amino acids and t
hen
absorbedintobloodstream.Ami noacidsar ebrokendownf urt
herand
catabol
ism begi
nswi t
hr emovalofnitr
ogent henami neisremov edand
endsupi nuri
ne.
Theremai ni
ngporti
onofami noacidarecall
edketoacids.
Ketoacidsareconver
tedintochemical
sthatcanenterkrebscycl
e.
Absor
pti
onofaminoacids
Theabsorpt
ionoccur
sinthesmal
lint
est
ineespeci
all
yatduodenum and
j
ejunum.Itisanact i
vepr ocessrequi
ri
ngenergyfr
om hydr
oly
sisofATP.
Themechani sm bywhi chami noaci
dsareabsor
bedare-
1.Carr
ierprotei
ntransport
2.Glut
athionetr
ansportsy st
em
3.Faci
li
tateddif
fusion
4.Simplediff
usion
Carri
erpr ot eintransportsy stem-(secondaryacti
vet r
anspor t)
Itist hemai nsy stem whi chhel psi nabsorpt
ionofami noacidsusing
energyi nt hef orm ofATP.Theami noacidsar eabsor bedbysodi um
dependentami noaci dtranspor t
ers.Therearediff
erentcarr i
erpr
otei
nsfor
+
specifi
cpr otei
ns.Thecar r
ierproteinshaveonesiteforNa andonesi t
efor
aminoaci ds.
Itco-t
r anspor tami noacidandNa+f rom t
heintesti
nallument ocyt
osolof
i
ntestinalmucosalcel l.The absor bed amino acid ent ersthe portal
+ +
cir
culat i
on, whil
eNa i sextrudedoutofcellinexchangef orK.
Glutathionet r
ansportsystem-
Glutathione isused t ot r
ansport L ami no acidsi nt
ot he cy
tosolof
i
nt est
inal cel
lsusi
ngener gy.
The gl utathi
one reacts wit
h amino aci
ds int he presence ofglut
amyl
transpept i
dasetof orm glutamylami
noaci d.Itrel
easest heaminoacids
i
nt othecy t
osolofthecellwi t
hfor
mati
onof5- oxoprol
inewhichisusedfor
regener ati
onofglutathi
onet obegi
nanothercycle.
Faci
li
t ateddiffusion-
Few ami no acids aret
ranspor
ted by speci
almembr
ane t
ranspor
tby
faci
l
itateddiffusion
Si
mpl
edi
ffusi
on-
D-
Ami
noacidsar
eabsor
bedbysi
mpl
edi
ff
usi
on
Ni
trogenbalance(NB)
Ni
trogenbalancei sabal ancebet
weenNitr
ogeni ntake(i
ntheform of
di
etarypr
otein)andNi tr
ogenloss(
asundi
gestedproteini
nfeces,
NPNas
ur
ea,ammoni a,creat
ini
neandur i
caci
dinur ine,sweatandsali
vaand
l
ossesbyhair,nail
,ski
n).
NBi si
mpor tanti
ndefini
ng
1.Ov
eral
l pr
oteinmetaboli
sm ofanindi
vi
dual
2.Nutr
it
ionalnit
rogenrequi
rement.
I
tmaybeposi
ti
ve,
negat
iveandneut
ral
(zer
o).
Positi
ve nitrogenous bal
ance – the amountofni tr
ogen enter
ed the
organism ismor ethanamountofni t
rogenremovedf r
om theorgani
sm.I t
occursiny ounggrowingorgani
sm,duringrecov
eri
ngaftersever
ediseases,
at t he usi ng of anabol ic medicines pregnancy,l act
ati
on and
convalescences
Negativenit
rogenousbalance–t heamountofni t
rogenr
emov edf rom the
organi
sm ismor ethanamountofni trogenenteredtheor
ganism.I toccurs
i
nsenileage,destroyi
ngofmal ignantt umor,v
astcombustions,poisoning
bysomet oxi
ns.Highlossoftissuepr otei
nsinwast i
ngdi
seaseslikeburns,
hemorrhageandki dneydiseaseswi thalbuminurea(Hi
ghbr eakdownof
ti
ssueprotei
ns)inhypert
hyroi
dism, f
ev er,
inf
ecti
on
Zeronitr
ogenousbalance– t heamountofni t
rogenremovedfr
om t
he
organi
sm isequalt otheamountofni tr
ogenent er
edt heor
gani
sm.It
occursi
nhealthyadul
tpeople
Normaladult
:will
beinnit
rogenequi
l
ibr
ium,Losses=Intake
Adef
ici
encyofevenoneaminoacidresul
tsi
nanegativ
eni
tr
ogenbal
ance.
I
nthi
sstat
e,moreprot
eini
sdegradedthansy
nthesi
zed.
Met abol
ism ofaminoacid
The ami no acids t
hatar e absorbed,may be used foranaboli
sm or
cataboli
sm.Eachdayabout400gofbodypr otei
nsaredegradedtoamino
acidsoutofwhi ch75-80%isreusedf orsy
nthesisofprotei
nsand20-25%
arecatabol
isedforenergy
.Themaj orsit
eofami noaci
ddegradat
ionisl
iver
.
Theaminoaci
dcat abolism removestheaminogr oupandcarbonskel
eton.
Theammoniathati spr oducedfr
om aminogr oupistoxi
ctoourbodyand
sohastobeel
iminat edt hr
oughureacycl
e.Thecar bonskel
etoni
susedf or
for
mati
onofglucose, acetylCoA,
ketonebodies,nonessent
ialaminoacids
orCO2andH2O
Aminoacidcatabol
ism
Theaminoacidcataboli
sm i
ncludes
1.Catabol
ism ofaminogroupnitr
ogen
2.Catabol
ism ofcarbonskelet
onofaminoaci
d
1.
Cataboli
sm ofami nogroupni
tr
ogen
I
toccursinfourst ages
1.Transami nation
2.Deami nation
3.Ammoni at r
ansport
4.Ureagenesi s
Transamination-
I
tisthepr ocesswher
etheaminogr
oupofanaminoaci
distr
ansfer
redby
tr
ansaminaset oaket
oaci
dfor
minganot
herαket
oaci
dandanaminoacid.
Heretheaminogr
oupi
str
ansferr
edfrom anaminoacidt
oaketoaci
danda
new aminoaci
dandanew ketoaci
disformed.Itoccur
sint
hecy t
osolof
l
iver
.
Transaminati
onisar ever
sibl
eprocessandthuscanbeusedforsynthesi
s
ofami noacidsf r
om αket oacids.Theexcessaminoacidsaredivert
ed
towardsenergyproducti
on.
The enzy mes catalyzi
ng thi
sr eacti
on are cal
l
ed t
ransaminases or
aminotransf
erase.
The mostcommon ar e al
ani
ne ami
notr
ansfer
ase (glut
amat
e pyruv
ate
tr
ansami
nases)and aspi
rat
eaminotr
ansf
erase( gl
utamateoxal
oacet
ate
tr
ansami
nases)
Alani
ne aminot
ransf
erase alanine + α-
ket
ogl
utar
ate ⇔ py
ruv
ate
+glut
amat
easpar
tateaminot
ransferase
Aspar
tat
e+α-
ket
ogl
utar
ate⇔ oxal
oacet
ate+gl
utamat
e
Aminotr
ansferasesfunnelα-
aminogroupsf
rom avar
iet
yofami
noacidsto
α-
ketogl
utar
atewi thglutamat
ef or
mationGlut
amatecanbedeaminated
wi
thNH4+r elease
Glutamatethatisfor
med by t
ransami
nati
on ent
erst
he nextst
ep of
oxidat
ivedeami
nat
iont
orel
easeammonia.
Deami nat i
on-
Itisthepr ocessinwhi chtheami nogroupremov edfr
om theaminoacidto
conv er
tintoammoni a.
Thispr ocessoccur sinli
verandkidney
The gl utamat et hat is produced by pr ocess of transami
nati
on is
transported tothemi tochondri
af ordeamination.Thenonni t
rogenous
portionofmol ecul
ei sconv er
tedtocarbohy
dr at
esorfats.
Ther
earetwodeaminati
onprocesses
Oxi
dati
vedeaminati
on
Nonoxidat
ivedeaminat
ion
Oxidati
vedeami nati
on-itoccurswit
ht hehelpoft woenzymesnamel y
glutamate dehy
drogenase and ami
no acid oxi
dase.Itis an oxi
dati
ve
reacti
onthatoccursunderaerobi
ccondi
tionsi
nallti
ssuesespeci
all
yli
ver
.
Heret heami noacidisconv ert
edint
ot hecorrespondi
ngketoacidby
removalofaminegr
oupasammoni
a.Thi
sami
negr
oupi
srepl
acedbya
ketonegr
oup.
Theenzymegl
utamat edehydr
ogenaser
emov
est
heami
nogr
oupf
rom t
he
gl
utmateandr
eleasesitasammonia.
Theenzymesami
noaci doxi
daser
emovest
heami
nogr
oupf
rom ot
herL-
aminoaci
dsandr
eleasesi
tasammoni
a.
Non-oxidati
vedeaminati
on-occur
swi
tht
hehel
pofenzy
mesami
noaci
d
dehy
dr ataseanddesul
phydr
ase
Dehydr
atase deami
nat
es ami
no aci
ds cont
aini
ng hy
droxy
lgr
oups l
i
ke
ser
ineandthr
eonine
Desulphy
drasedeaminat
esami
noaci
dscont
aini
ngsul
phurl
i
kecy
stei
ne,
cyst
ineandmethioni
ne
Ser
ine ser
inedehy
drat
ase py
ruv
ate+NH4
Cy
stei
ne ser
inedehy
drat
ase py
ruv
ate+NH4
Ammoni
atr
anspor
t-
Theammoni ar
eleasedafterdeami
nati
onprocessistr
ansport
edtotheliv
er
forformati
onofur eawhi chisthenexcret
edbyki dneys.Someoft he
ammoni aproducedi nthel i
vermaybeusedf orsynt
hesi
sofnitrogenous
moleculesl
ikenucleot
ides.
Ammoniaisat oxi
cproductsot
hebrai
nti
ssuesar
ev er
ysensi
ti
veto
ammoniaandi ft
herei
sammoniaint
oxi
cat
ion,t
heper
sonwil
lgoi nt
o
comat
osestat
e.
Theexcessammoni amustconver
ttonontoxiccompoundwhichcan
funct
ionasaminogroupcar
ri
eri
nthebl
oodtot
ranspor
tammoniaf
rom t
he
ti
ssuestot heli
ver
.Thepr i
marycarr
ieri
nthebloodisglut
amineand
al
ani
ne.
Glut
aminetransportammoniafr
om brainandot hert
issuestotheli
verwit
h
the hel
p ofenzy me gl
utamate dehydrogenase while al
ani
ne tr
ansport
ammoni afr
om themuscletotheli
verbyenzy mealanineaminotr
ansfer
ase.
Ur
eacy
cle/or
nit
hinecy
cle/
krebs-
hensl
eitcy
cle
Ur
eacy
clei
sabi
ochemi
cal
react
ioni
nwhi
chur
eai
sfor
medf
rom ammoni
a.
Ammoniai
sv erytoxi
c,par
ti
cul
arl
ytothecentralner
voussyst
em.
Ammoniatr
av el
st otheli
verf
rom ot
hertissues,mainl
yinthef
orm of
al
ani
neandglutamine.
Wit
hthe hel
p ofcert
ain enzy
me int he l
i
verthe CO2 combi
nes wi
th
ammoni
atoform al
esstoxi
cnit
rogenouscompoundurea.
Thi
sureaisrel
easedfr
om t
heli
verintot
hebloodst
ream al
ongwi
thwat
er
andi
stranspor
tedtot
heki
dney
sf orexcr
eti
on.
Theureaexcretedeachdaybyaheal t
hyadult(
about30g)accountsf
or
about90%oft heni
trogenousexcr
etor
yproducts.
Ureaisformedi ntheureacyclefr
om NH4+,CO2,andt henit
rogenof
aspar
tate.
St
epsofur
eacy
cle-
1.Formati
onofcar bamoy lphosphate-ammoni acombi
neswit
hcarbon
dioxi
de by using 2ATP i nt he presence ofenzyme car
bamoyl
phosphat
esy nthetaseiandco- enzymeN- acet
ylgl
utamat
et of
orm
carbamoylphosphate.
2.Synthesi
sofcitrul
li
ne-Orni
thi
nereact
swithcarbamoylphosphat
eto
form ci
tr
ull
ineinthepresenceoforni
thi
netranscar
bamoy l
ase.The
cit
rul
li
netransport
erthent r
anspor
tscit
rul
li
nef r
om mitochondr
iai
al
mat
ri
xtocy
tosol
wher
ethenextr
eact
ionoccur
s.
3.Synthesi
sofargini
nosucci
nat
e-Ci
tr
ull
inecombineswit
haspar t
atet
o
for
m ar gini
nosucci
nate i
n the presence of argi
ninosucci
nat
e
synt
hetaseenzyme.
4.Cleavageofar gi
ninosuccinate-Argini
nosucci
nateiscleavedtoform
argini
neandf umar ateinthepr esenceofenzymear gininosucci
nat
e
l
y ase.Thisreacti
onoccur sint hecy tosol
.Fumaratepr oductisan
i
mpor tantl
inkbetweenur eacy cleandcitri
caci
dcy cl
e.Thef umarat
e
thatisf or
medi st ransport
edbackt ot hemitochondrialmatri
xto
entertheTCAcy cl
e.
5.Cleavageofar ginine-Ar
ginineiscleavedbyenzymear gi
naset
of or
m
ureaandr egener ateorni
thine.Theor nit
hinei
st r
ansport
edbackt o
mitochondr almat ri
xtocont inuet hecyclewhil
et heureadi
ffuses
fr
om t heliv erintot hebloodst ream andi st
ranspor
tedtokidneys
wherei ti
sf i
lteredandexcr etedintheuri
ne.
2.Cat
abol
ism ofcar
bonskel
etonofami
noaci
ds
I
ti st he pr
ocess bywhi ch biologi
calcell
s buil
d ormanuf act
ure new
prot
ei ns
Thei nformationtobuildnewpr ot
einscodedinthestructur
eofDNAi nt he
nucleusoft hecells.Theinformat i
onfrom DNAiscarri
edt othecyt
oplasm
witht hehelpofmRNA whi chi stheninter
pret
edbyt RNA anddiff
erent
ty
pesofpr oteinsaresynt
hesi z
ed.
St
epsofbiosynt
hesis
1.Transcr
ipt
ion
2.Transl
ati
on
Transcri
ption-i ti st
he f i
rstst ep i
n prot
ein bi
osynt
hesi
sin whi ch the
i
nformation f rom t he DNA st r
uctur
e i s tr
anscri
bed int
o mRNA.
Transcri
ptioni st hesynthesisofmRNA f rom aDNA t emplat
e.A smal l
porti
onoft heDNAdoubl ehelixuncoilsandacompl ementarystrandof
RNA i s synthesized wit
ht he hel
p ofRNA pol ymerase.The RNA t hat
contai
nst hemessaget hatwascodedi ntheDNAi scal
ledmessengerRNA
(mRNA) .The RNA st rand i sthe rever
se complementofor i
ginalDNA
sequence.
Translat
ion-i
tist
heprocessinwhichpr ot
einsaresynthesi
zedinthe
ri
bosomes.The pr
ocessofmRNA t ransl
ati
on beginsfr
om the 5’end
towards3’endast hepol
ypept
idechaini
ssy nt
hesi
zedfrom i
tsamino
ter
minalend.
Theprocessoftranslat
ionbeginswithbi
ndi
ngofmRNAt otheri
bosomes.
ThereisaspecialtypeofRNAcal l
edtRNAt hatint
erpr
etsthecodonson
mRNA.I tmat
chest heami noacidspr
esenti
nt hecel
ltothecorr
ectcodons
onthemRNAst r
and.
Theat t
achmentofaminoacidstospeci
fi
ctRNAoccur swiththehelpof
enzymesami noacy
ltRNAsynthet
ase.Theenzymerecognizestheamino
aci
daswel lasthespeci
fi
ct RNA towhichtheami no acidshoul
dbe
att
ached.ThetRNAhasanant i
codonwhichrecogni
zesthecodonoft he
mRNA.
St
epsi
ntr
ansl
ati
on
I
nit
iat
ion
El
ongat
ion
Ter
minat
ion
Init
iati
on-t he st
artcodon on mRNA( AUG) init
iat
es the process of
transl
ation.AUGrepresent
stheami noacidmethi
onineiti
sthefirstami
no
acidt hatisbroughtintotheribosome.Theami noacidmethioninefi
rst
attachesitsel
ftothetRNAthathastheanti
codonUAC.
Elongation-itist headdi ti
onofami noacidsbypept idebondst oform
polypeptidechains.Ther i
bosomeshavetwosi tesPandAsi t
e.Thef i
rst
tRNAwi t htheanticodonf oraminoacidmet hi
onineatt
achestothePsi te
of t he ribosome whi ch cor r
esponds t
ot he star
t codon AUG.t he
subsequentt RNA wi t
ht heboundami noaci dandant icodonenterthe
ri
bosomeandat t
achest ot heA siteattheircorr
espondingcodon.The
compl ement arymat chingoft hecodonandt heanticodonensuresthe
correctsequenceofami noacids.
Terminati
on-whent heribosomer eachesthecodonUAG,UAAORUGAon
mRNA ,t hepr oteinsy nthesi
si sterminat
ed.Thiscodoniscall
edstop
codons.Terminationbegi nswhent hestopcodonappearsintheAsi
teof
theri
bosome.Thepol ypeptidechai
nishy dr
olysedandi
srel
easedf
rom t
he
tRNAallowingtheproteint oexi
stfrom t
heribosome.
Post
-Tr
ansl
ati
onalModi
fi
cat
ion(
PTM)
Thechemicalmodifi
cat
ionofaprot
einaf
teri
tst
ransl
ati
oni
sknownas
Post
-Tr
anslat
ional
Modif
icat
ion.
I
mpor
tanceofPost
-Tr
ansl
ati
onalModi
fi
cat
ion
Regul
ati
onofpart
icul
arpr
otei
nsequencebehav
iori
nmostoft
he
eukar
yot
icor
gani
sms.
Hel
pi nut i
l
izi
ngi denti
calprotei
nsf ordiff
erentcellul
arfuncti
onsin
di
ffer
entcellt
ypes.
Pl
ayacr uci
alroleingenerat
ingthehet er
ogeneityinprot
eins.
Contr
ibutetowardsbiologi
calprocessesanddi seasedconditi
ons.
Pl
ayani mportantpartinmodifyi
ngt heendpr oductofexpressi
on.
Ty
pesofpostt r
ansl
ati
onmodi
fi
cat
ion
1.Tri
mmi ng
2.CovalentModifi
cati
on
3.Ubiquit
inati
on
Tr
immi
ng-Remov
alofapar
toft
het
ransl
atedsequence.
Pr
oteases Pr
otei
nact
ivat
ion.
Coval
entModi fication
1.Phosphor ylati
on
2.Glycosy lation
3.Hy droxy l
ation
4.Car boxy l
ation
5.Biotinylati
on
6.Acet yl
at i
on
7.Met hylation
8.Alky l
ati
on
9.Glutamy l
ation
10. Lipoy lat
ion
11. Sulfat i
on
Phosphoryl
ati
on-Theaddi
ti
onofaphosphate(PO4)groupt
oaprot
einora
smallmolecul
ecall
edphosphor
ylat
iont
hiscanoccuronSeri
ne,
Thr
eonine,
Tyr
osine.
ATP+Pr
otei
n pr
otei
nki
nases phosphopr
otei
n
Gl
ycosy
lat
ion-Theaddi
ti
onofsacchar
idet
oapr
otei
noral
i
pidmol
ecul
e.
N-Li
nkedGl
ycosy
lat
ion-at
tachedtot
heni
tr
ogenofAsparagi
ne
O-Li
nkedGly
cosyl
ati
on– attachedt
othehydr
oxyloxygenofSer
ineand
Theri
oni
ne
Hy
droxy
lat
ion-Theaddi
ti
onofhy
droxy
lgr
oupt
opr
oli
neofpr
otei
n
Car
boxy
lat
ion-Theaddi
ti
onofcar
boxy
lgr
oupt
ogl
utamat
e.
Bi
oti
nyl
ati
on-Theaddi
ti
onofbi
oti
ntopr
otei
nornucl
eicaci
d
Acet
ylat
ion-Theaddi
ti
onofanacet
ylgr
oup,usual
l
yatt
heN-t
ermi
nusof
t
heprotei
n.
Met
hyl
ati
on-Theaddi
ti
onofanal
kyl
group(
e.g.met
hyl
,et
hyl
)
Alkyl
ati
on-Theaddi
ti
onofamet
hylgr
oup,usual
l
yatl
ysi
neorar
gini
ne
resi
dues
Glut
amy
lat
ion-Cov
alentl
i
nkageofgl
utami
caci
dresi
duest
otubul
i
nand
someot
her
Li
poy
lat
ion-Theat
tachmentofl
i
poat
efunct
ional
i
ty
Sul
fat
ion-Theaddi
ti
onofasul
fat
egr
oupt
oat
yrosi
ne.
Ubiquit
inati
on-Hi ghl
yspeci
fi
cdegr adati
onofpr ot
eincanbeachi
eved
throught headdit
ionofoneto severalubiqui
ti
nmol ecul
est
o atar
get
protei
n.Theprocessiscal
l
edUbiqui
ti
nation.
I
mpor
tanceofanal
ysi
sofpostt
ransl
ati
onmodi
fi
cat
ion
Theseareparti
cul
arl
yimport
antf
orthestudyofhear
tdi
sease,
cancer
,
neurodegener
ati
vedi
seasesanddiabet
es.
Thesear
ekeymechani
smst
oincr
easepr
oteomi
cdi
ver
sit
y.
Pr
otei
ntar
get
ing
Itisthebiol
ogicalmechani sm bywhi chpr oteinsaret ransport
edt otheir
appropri
atedestinat
ioninsidethecellorout sideofi t.Thedel i
veryoft he
protei
ndependsont heinformati
oncont ainedi nthepr otei
nitsel
f.Correct
sorti
ngisimportantforcel
l aserr
orscanl eadtodi seases
St
ruct
ureoft
RNA
t-
RNA(transf
erRNA)i
sal
sonamedasS-
RNA(
sol
ubl
eorsuper
nat
antRNA)
andadaptorRNA.
Aminoacidaccept orarm
Doublehelical(both5’and3’endsoft
RNA)
7basepairsunpai red
At3’end,5’CCA3’ prot
rudeswith–OHatthet
ip
Sit
eforattachmentofami noaci
d
- COOHofspeci fi
caminoacidjoinswi
th–OHofAi
nCCAt
ofor
m
aminoacyl tRNAEst erbond
Darm •DHUorDar m
Thisarm consist
sofst em andloopwit
hunusual pyr
imi
dine
nucleot
idedihydrour
acil.
4bpst em withaloopcont ai
ndihydr
ouri
dine
Recogniti
onsiteforthespecif
icenzymeami noacyl
-t
RNAsynthet
ase
thatacti
vat
etheami noaci
d
Playaimportantr
oleinthest
abi
l
izat
ionoft
het
RNA'
ster
ti
ary
struct
ure.
TyCar m
TyCar mi snamedf orthepr esenceofsequenceTy C(thymine–
pseudour i
di ne(y)–cy tosine),wherepseudour idineisunusualbase.
Thisar m alsoconsi stsofstem andl oop.
Stem cont ains5basepai rs;outermostoft hesepai r
sisC- G.Loop
contains7unpai r ednucleotides
Thisloopcont ai
nsar i
bosomer ecogniti
onsi t
e.
Thisar m alsocont ainsstem andl oop.
Stem consi stsof5basepai r sandloop( call
edasant icodonloopor
l
oopI I)cont ai
ns7unpai r
ednucl eotides.
Outoft hese7unpai r
ednucl eoti
dest hemi ddlethreeform anti
codon.
Anti
codonr ecogni zesandcodonofmRNAandbi ndst oi
t.
Funct
ionsoftRNA-
Helpi
nt her
ecogni
ti
onofAmi
noacy
ltRNAsy
nthet
aseenzy
me
Pi
cksupspeci
fi
cami
noaci
dfr
om cy
topl
asm andcar
ri
est
osi
teof
pr
otei
nsynt
hesi
s
At
tachesi
tsel
ftor
ibosomei
naccor
dancewi
thsequencespeci
fi
edby
mRNA
Tr
ansmi
tsami
noaci
dtopol
ypept
idechai
n
Par
tici
pat
einnonprot
einsynthet
icpr
ocessessuchasapr
imer
dur
ingrev
erset
ranscr
ipt
ioninret
rovi
rusl
if
ecycles
I
mpor
tantquest
ions-
Giveanaccountofdi
gest
ionandabsor
pti
onofpr
otei
ns-August
2010(10marks)
Ur
eacy
cle-August2010(
5mar
ks)
Postt
ransl
ati
onmodi
fi
cat
ioni
npr
otei
ns-
Aug2009-
(5mar
ks)
St
ruct
ureandf
unct
ionsoft
RNA-
Aug2009-
(5mar
ks)
Essent
ial
ami
noaci
ds-Aug2009(
2mar
ks)