kadar urea

8/21/2019 kadar urea

1/32


2/32

TUJUAN PEMBELAJARAN :

Mahasiswa mampu menjelaskan :

Organ yang berperan dan lokasi terjadinya

siklus urea

5 tahap siklus urea

Mekanisme regulasi siklus urea dan peranan

siklus urea dalam metabolisme tubuh


3/32

Sumber Pustaka

• DB Marks. 2000. Biokimia Kedokteran Dasar. Jakarta.

EGC• DK Kusmiyati, Setyawati AN, Ngestiningsi D,

Kristina !N. 20"". Buku A#ar Biokimia. Bagian

Biokimia $aku%tas Kedokteran &ni'ersitas

Di(onegoro. Semarang.


4/32

SIKLUS UREA

• Jalur Utama pembuangan amonia

• Pembentukan urea hanya terjadi di

Hepar.

• Hanya 2 reaksi pertama terjadimitokondria

• emua reaksi setelahnya terjadi di

sitosol.


5/32

Transport of

ammonia to liver


6/32

$rom most tissues

$rom mus)%e

G%u)ose

Urea

NH3

*2+

Glutaminase

Glutamate

dehydrogenase

ketog%utarate

G%utamate

A%anine-yru'ate

ALT

G%utamine

i'er

A%anine )y)%e


7/32

teps of Urea Cycle


8/32

Ma%ate

Mito)ondrion

2 A!- / *C+ / N* Car1amoy% (os(ate / 2 AD- / -i

-i

Citru%%ine

Citru%%ine

A!-

AM- / --i

As(artate

Arginino

su))inate

+a%oa)etate

$umarate

Arginine

*2+

&rea

+rnitine Urea cycle

Cytoso%

"

2

3

4

+rnitine


9/32

5EAKS6 !A*A- "

•En7im yang 1er(eran

carbamoyl phosphate

synthetase-I •

Mem1utukan 2mo%eku% A!-.•En7im ini kun)i sik%us

urea•Diakti8kan o%e N

a)ety% g%utamate.


10/32

Mito)ondrion


-i

Citru%%ine

Citru%%ine

A!-

AM- / --i

As(artate

Arginino

su))inate

+a%oa)etateMa%ate

$umarate

Arginine

*2+

&rea

+rnitine Urea cycle

Cytoso%

"

2

3

4

+rnitine


11/32

5EAKS6 !A*A- 2

•5eaksi ter#adi di

mitokondria•En7im yang 1er(eran

ornithine

transcarbamoylase•Kar1amoi% 8os8at /

ornitine sitru%in•Sitru%in ke%uar

menu#u sitoso%


12/32

Mito)ondrion


-i

Citru%%ine

Citru%%ine

A!-

AM- / --i

As(artate

Arginino

su))inate

+a%oa)etateMa%ate

$umarate

Arginine

*2+

&rea

+rnitine Urea cycle

Cytoso%

"

2

3

4

+rnitine


13/32

5EAKS6 !A*A-

•!er#adi di sitoso%•En7im 9

argininosuccinate

syntethase•Sitru%in / as(artat

arginino suksinat•5eaksi ini ATP

dependent,

mengasi%kan AM-

dan -.


14/32

Mito)ondrion


-i

Citru%%ine

Citru%%ine

A!-

AM- / --i

As(artate

Arginino

su))inate

+a%oa)etateMa%ate

$umarate

Arginine

*2+

&rea

+rnitine Urea cycle

Cytoso%

"

2

3

4

+rnitine


15/32

5EAKS6 !A*A- 3

•

En7im 9argininosuccinate

lyase

•arginino suksinat

arginin / 8umarat


16/32

Mito)ondrion


-i

Citru%%ine

Citru%%ine

A!-

AM- / --i

As(artate

Arginino

su))inate

+a%oa)etateMa%ate

$umarate

Arginine

*2+

&rea

+rnitine Urea cycle

Cytoso%

"

2

3

4

+rnitine


17/32

5EAKS6 !A*A- 4

•En7im 9 arginase

•Arginin urea /

ornitine

•&rea masuk a%iran

dara gin#a%ke%uar %ewat urin

•+rnitine

mitokondria


18/32

Mito)ondrion


-i

Citru%%ine

Citru%%ine

A!-

AM- / --i

As(artate

Arginino

su))inate

+a%oa)etateMa%ate

$umarate

Arginine

*2+

&rea

+rnitine Urea cycle

Cytoso%

"

2

3

4

+rnitine


19/32

$&MA5A!

•

Dikon'ersimen#adi as(artat

•En7im 9 ma%ate

deydrogenase

•!er1entuk

oksa%oasetat


20/32

!"#$%& "%'U U!(&

• As(artate / N*0 / C+2 / A!- &rea / 8umarate /

2AD- / AM- / 2 -i /--i

• 3 A!- di1utukan untuk mem1entuk " mo%eku% &rea.

• Sik%us &rea meru(akan 5eaksi 6rre'ersi1e%

• -enting untuk mem1uang amonia dari tu1u

• *i(eramonia toksik


21/32

ources of

urea nitrogen


22/32

+rnitine

ketoa)ids

Amino a)ids

$umarate

Argininosu))inate

Amino a)ids

ketoa)ids G%utamate

As(artate

+a%oa)etate

ketoa)ids

&rea

)y)%e

Citru%%ine

Car1amoy%

(os(ate

C+2

NAD* /

NAD/

G%utamate

ketog%utarate

&rea

Arginine

N*

Sources of urea

nitrogen

• +ne nitrogen o8 te

urea mo%e)u%e is

su((%ied 1y 8ree N*0,and te oter

nitrogen 1y

as(artate.

• G%utamate is te

immediate (re)ursor

o8 1ot ammonia

wi) in turn,

gaters nitrogen

8rom oter amino

a)ids


23/32

Regulation of

urea cycle

$ine regu%ation Gross regu%ation


24/32

NA)ety%g%utamate is an essentia% a%%osteri) a)ti'ator 8or

)ar1amoy% (os(ate syntetase 6, te rate%imiting ste( in te

urea )y)%e. NA)ety%g%utamate is syntesi7ed 8rom a)ety%CoA and

g%utamate, in a rea)tion 8or wi) arginine is an a)ti'ator.

6 $ine regu%ation

A)etate

Hydrolase

G%utamate A)ety% CoA

Synthetase Arginine

NA)ety%g%utamate CoA

/


25/32

An in)rease in te su((%y o8 amino a)ids to te %i'er, su) as

o))urs on a ig (rotein diet, during te administration o8 te

(rotein )ata1o%i) ormones, and during (ro%onged star'ation,

in)reases te syntesis o8 te urea )y)%e en7ymes "0208o%d. !is

in)reases urea 8ormation.

66 Gross regu%ation


26/32

Fate of urea


27/32

• !e urea 8ormed 1y te %i'er goes, 'ia te 1%ood :(%asma %e'e%

"040 mg;d


28/32

Hyperammonemia


29/32

A!-

G%u)ose

G%y)o%ysis

-yru'ate

+a%oa)etate A)ety% CoA

!CA

Citrate

6so)itrateNAD*NAD

ketog%utarate

N*

NAD*NAD

G%utamate

N*

G%utamine

AD-

Me)anism o8 ammonia toi)ity

• !e toi)ity is tougt to resu%t, in(art, 8rom a si8t in te e=ui%i1rium

o8 te g%utamate deydrogenaserea)tion towards te dire)tion o8g%utamate 8ormation.

• !is de(%etes ketog%utarate, anessentia% intermediate in te )itri)a)id )y)%e, resu%ting in a de)rease in

)e%%u%ar oidation and A!-(rodu)tion. !e 1rain is (arti)u%ar%ysensiti'e to y(erammonemia,1e)ause it de(ends on te )itri) a)id)y)%e to maintain its ig rate o8energy (rodu)tion.


30/32

Ma#or ty(es o8 y(erammonemia

". A)=uired y(erammonemia9 Cirrosis o8 te %i'er )aused 1y a%)oo%ism, e(atitis, or 1i%iary

o1stru)tion may resu%t in 8ormation o8 )o%%atera% )ir)u%ation around te%i'er.

2. *ereditary y(erammonemia :meta1o%i) disorders o8 te urea )y)%e


31/32

• *owe'er, wen te %i'er 8un)tion is )om(romised, due

eiter to geneti) de8e)ts o8 te urea )y)%e, or %i'er disease,

1%ood %e'e%s )an rise a1o'e "000 mmo%;.

• *y(erammonemia is a medi)a% emergen)y, 1e)ause

ammonia as a dire)t neurotoi) e88e)t on te CNS.

• $or eam(%e, e%e'ated )on)entrations o8 ammonia in te1%ood )ause te sym(toms o8 ammonia intoi)ation, wi)

in)%ude tremors, s%urring o8 s(ee), 'omiting, )ere1ra%

edema, and 1%urring o8 'ision.

• At ig )on)entrations, ammonia )an )ause )oma and

deat.


32/32

kadar urea

Documents

Transcript of kadar urea