Metabolizam i Regulacija
-
Upload
fuad-zecirovic -
Category
Documents
-
view
80 -
download
3
Transcript of Metabolizam i Regulacija
![Page 1: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/1.jpg)
Regulacija metabolizma
Biohemija 2011/12
Prof. dr G. Grubor-Lajsic
![Page 2: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/2.jpg)
Da se podsetimo...
funkcija metabolizma je:
• da obezbedi energiju, razgradnjom energijom bogatih
nutrijenata ili koriscenjem sunceve energije
• da molekule nutrijenata prevede u prekursore za
izgradnju makromolekula i celiskih komponenti
• da formira i razgradi biomolekule za specijalizovane
funkcije celije
![Page 3: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/3.jpg)
Razliciti su putevi katabolizma i anabolizma
KATABOLIZAM
ANABOLIZAM
![Page 4: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/4.jpg)
• mnogi metabolicki
putevi su nezavisni
• komunikacija
izmedju metabolickih
puteva je koordinirana
i kontrolisana
![Page 5: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/5.jpg)
![Page 6: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/6.jpg)
Regulacija metabolizma
• prostornim rasporedom enzima i metabolita
– raspolozivost supstrata (kompartmenizacija)
– razdvojenost suprotnih puteva (sinteza m.k. u citosolu,
razgradnja u mitohondrijama)
• enzimima
• hormonima (koordiniraju metabolizam izmedju
razlicitih tkiva)
– cesto kontrolisu reverzibilnu modifikaciju enzima
– koordinisu energetski status celije
![Page 7: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/7.jpg)
Mehanizmi kontrole enzimima
• kontrola kolicine enzima
– promenom genske ekspresije
– degradacijom enzima
• kontrola kataliticke aktivnosti (regulatorni enzimi)
– nekovalentne interakcije
• reverzibilna alosterna kontrola (npr. kontrola povratnom spregom, odgovor brz)
– kovalentne modifikacije
• fosforilacija, ubikvatinizacija…
![Page 8: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/8.jpg)
Koji enzim je regulatorni?
• katalise reakciju koja odredjuje brzinu celog
metabolickog puta
• reakcija koju katalise je najcesce na pocetku
metabolickog puta
• katalise nepovratnu reakciju
– za koju je potrebna energija
– cesto nastaje proizvod koji je fosforilisan
![Page 9: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/9.jpg)
Alosterna kontrola
• alosterni aktivator/inhibitor
• vezuje se za enzim (ali ne za aktivno mesto)
• promovise ili inhibira enzimsku aktivnost
drugo mesto
![Page 10: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/10.jpg)
Alosterna aktivacija
supstrat
alosterni efektor
![Page 11: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/11.jpg)
Alosterna inhibicija
supstrat
alosterni efektor
![Page 12: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/12.jpg)
Molekuli koji mogu da budu alosterni
efektorni molekuli
• krajnji produkti metabolickog puta
– povratna sprega (feedback inhibicija)
• supstrati samog metabolickog puta
– kao aktivatori “vuku” reakciju napred
• indikatori energetskog stanja
– ATP/ADP/AMP
– NAD/NADH
– citrat i acetil CoA
![Page 13: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/13.jpg)
Inhibicija povratnom spregom
(“feedback” inhibicija)
enzim 4enzim 2enzim 3
enzim
1
enzim 5
krajnji
proizvodsupstrat
Promene u celiji, kao rezultat
specificne aktivnosti, prekidaju
aktivnost koja je dovela do
te promene
![Page 14: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/14.jpg)
Kovalentna regulacija enzimske aktivnosti –
fosforilacija/defosforilacija
• dodavanje ili eliminisanje fosfatne grupe na
aminokiselinskim ostacima proteina
(posttranslaciona modifikacija proteina) menja
enzimsku aktivnost
• najcesce na aminokiselinama : serin, treonin ili
tirozin
![Page 15: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/15.jpg)
Kovalentna regulacija enzimske
aktivnosti – delimicna proteoliza
• specificna proteoliza moze da aktivira odredjene
proteine i enzime (zimogene)
– digestivni enzimi
– proteini koagulacije krvi
– peptidni hormoni (insulin)
![Page 16: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/16.jpg)
neki proteini se sintetisu kao neaktivni prekursori
(zimogeni ili proenzimi)
![Page 17: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/17.jpg)
Tipovi regulatornih mehanizama
• nekovalentne interakcije
– alosterna modulacija enzima
– protein-protein interakcija
• kovalentne modifikacije enzima
• promene u zastupljenosti enzima
![Page 18: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/18.jpg)
Promene u kolicini prisutnih enzima
• inducibilni u odnosu na konstitutivne enzime
• indukcija je rezultat povecanja brzine transkripcije
gena
– hormoni aktiviraju transkripcione faktore
• povecava se sinteza specificnih mRNK
• povecava se sinteza specificnih enzima
![Page 19: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/19.jpg)
Primer - kontrola energetskog metabolizmam
• da li ce metabolizam hrane, kao energetskog
goriva, biti usmeren ka potrosnji ili deponovanju
energije zavisi od
– hormona
– koncentracije raspolozivog goriva
– zahteva organizma za energijom
![Page 20: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/20.jpg)
Signalni molekuli, receptori, medjucelijska
komunikacija
• hormoni i neurotransmiteri
– aminokiseline i njihovi derivati
– mali proteinski molekuli (peptidni hormoni)
– derivati holesterola (steroidni hormoni)
– modifikovane masne kiseline (eikozanoidi)
![Page 21: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/21.jpg)
Signalni molekuli deluju preko receptora
![Page 22: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/22.jpg)
Od hemijske prirode signalnih molekula zavisi
gde je receptor
• prema hemijskoj prirodi signalni molekuli su
– hidrofilni (ne mogu da prodju kroz celijsku
membranu)
• modifikovane aminokiseline (adrenalin)
• peptidni hormoni (glukagon)
– hidrofobni (lipofilni) (mogu da prodju kroz
celijsku membranu)
• tireoidni i steroidni hormoni i eikozanoidi
(ima izuzetaka)
![Page 23: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/23.jpg)
• intracelularni receptori
– lipofilni signalni molekuli
• steroidni hormoni, vitamin D, retinoidi,
tiroksin
– vezuju se za intracelularne receptore
• zajedno za regulatorne elemente na DNK
–menjaju brzinu transkripcije
– indukuju ili represuju transkripciju
![Page 24: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/24.jpg)
• receptori u celijskoj membrani
– za hidrofilne signalne molekule
• peptidne hormone, kateholamine,
neurotransmitere
• tri klase receptora
– receptori vezani za kanale
– kataliticki receptori
– receptori vezani za G protein
![Page 25: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/25.jpg)
![Page 26: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/26.jpg)
Razlike u delovanju
hidrofilnih (peptidi,
proteini, derivati
aminokiselina) i
hidrofobnih
signalnih molekula
(steroidi, tiroidni
hormoni)
![Page 27: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/27.jpg)
Signalni molekuli se dele i prema…
• podela prema mestu produkcije i ciljnog mesta
– autokrini (eikozanoidi) –deluju na celiju koja ih proizvodi (lokalni medijatori)
– parakrini – deluju na susedne celije (histamin)
– endokrini – sintetisu se u celijama endokrinog sistema i transportuju putev krvi do ciljnog tkiva (adrenalin, insulin)
![Page 28: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/28.jpg)
• podela prema brzini odgovora
– odgovor brz (sekunde) – regulacija
metabolizma preko vec prisutnih enzima
(modifikacija-fosforilacija)
– odgovor polagan (sati, dani, nedelje) –
promena na nivou ekspresije gena (u
regulaciji rasta i diferencijacije)
![Page 29: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/29.jpg)
Signalna transdukcija
• hidrofilni signalni molekul, receptor integralni membranski protein , povezan sa
– jonskim kanalom – regulise permeabilnost membrane za jone
– sa G proteinom – aktiviraju se protein kinaze preko unutarcelijskih glasnika (sekundarnih glasnika)
– sa enzimskom aktivnoscu – citoplazmatski deo receptora ima tirozin kinaznu aktivnost i fosforilisu ciljne enzime u celiji
![Page 30: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/30.jpg)
![Page 31: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/31.jpg)
Unutarcelijski glasnici
• ciklicni AMP (cAMP)
• diacilglicerol (DAG) i inozitoltrifosfat (IP3)
• ciklicni GMP (cGMP)
![Page 32: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/32.jpg)
vezivanje hormona za receptor uzrokuje:
• GTP zamenjuje GDP • alfa subjedinica disosuje od beta i gama subjedinice G proteina• aktivira se (ili inhibira) adenilat ciklaza – nastaje cAMP (aktivira protein kinazu A)• cAMP se razlaze fosfodiesterazom (stimulisana insulinom, kofeinom…)
![Page 33: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/33.jpg)
aktivirana alfa
subjedinica G proteina
deluje i na fosfolipazu C
• nastaju dva glasnika:
DAG i IP3
• deluju na protein kinazu C i Ca
![Page 34: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/34.jpg)
![Page 35: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/35.jpg)
Metabolicki putevi
![Page 36: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/36.jpg)
Koenzimi oksidoreduktaza
![Page 37: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/37.jpg)
Figure 14-11
Redukcija NAD+ ili NADP+ do
NADH ili NADPH
![Page 38: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/38.jpg)
![Page 39: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/39.jpg)
Figure 14-13 part 2
Redukcija FAD u FADH2
![Page 40: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/40.jpg)
Pregled
oksidacionih
puteva katabolizma
biomolekula
![Page 41: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/41.jpg)
D-Glukoza
C OHH
C
C
HO H
OHH
C
CH
O
CH2OH
OHH
C
C
O
O
O-
CH3
ATP
fosfoglukozo izomeraza
heksokinaza(glukokinaza u jetri)
ADP
fosfofruktokinaza-1
Glukozo 6-P Fruktozo 6-P
Fruktozo 1,6-bisP
Gliceraldehid 3-P
1,3-bisfosfoglicerat
3-Fosfoglicerat2-FosfogliceratFosfoenolpiruvatPiruvat
piruvatkinaza
enolaza mutaza
fosfoglicerat kinaza
gliceraldehid 3-fosfatdehidrogenaza
triozofosfat izomerazaaldolaza
Dihidroksiaceton fosfat
NAD+
Pi
NADH + H+
H2OADPATP
ATP ADP
P
C
CH2OH
CH
O
OHH
C
C
C
HO H
OHH
C
CH2O
CH2O
OHH
O
P
C OHH
C
C
HO H
OHH
C
CH
O
CH2O
OHH
P
C
CH2
C
O
O
O-
P
C
CH2OH
CH2O
O
P
P
C
CH2O
C
H OH
O
O
ADP
ATP
C
CH2O
C
H OH
O
O-
P
PC
CH2OH
C
H O
O
O-
C
C
C
HO H
OHH
C
CH2OH
CH2O
OHH
O
P
P
P
Glikoliza
![Page 42: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/42.jpg)
Glikoliza - regulacija
![Page 43: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/43.jpg)
Glikoliza u aerobnim i anaerobnim uslovima
![Page 44: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/44.jpg)
Ulazak drugih
monosaharida
u glikolizu
![Page 45: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/45.jpg)
Metabolizam
galaktoze
![Page 46: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/46.jpg)
Metabolizam glikogena
![Page 47: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/47.jpg)
Regulacija glikogen fosforilaze
![Page 48: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/48.jpg)
Regulacija glikogen fosforilaze
![Page 49: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/49.jpg)
Glukoneogeneza
![Page 50: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/50.jpg)
Glukoneogeneza
![Page 51: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/51.jpg)
Glukoneogeneza - regulacija
![Page 52: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/52.jpg)
![Page 53: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/53.jpg)
Korijev ciklus
![Page 54: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/54.jpg)
Glukozo 6-P
glukozo-6-fosfat dehidrogenaza
6-Fosfoglukono lakton 6-FosfoglukonatRibulozo 5-P
C OHH
C
C
OHH
CH2O
OHH
C
H OCH2OH
C
C
C
HHO
OHH
O
C
C
H OH
OHH
CH2O
C
C
CH2O
OH +H
HO
Ribozo 5-P
Ksilulozo 5-P
6-fosfo glukonolaktonoza
fosfoglukonat dehidrogenaza
transketolaza
ribulozo 5-fosfat izomeraza
ribulozo 5-fosfat epimeraza
Sedoheptulozo 7-Ptransaldolaza
Gliceraldehid 3-P
Eritrozo 4-P
transketolaza
33 3
C OHH
C
C
HO H
OHH
C
CH
O
CH2O
OHH
P
C OHH
C
C
HO H
OHH
C
C
O
CH2O
H
O
P
3NADP+
3NADPH + 3H+
3H2O3H+
3
2
OKSIDACIONA FAZA
NEOKSIDACIONA FAZA
C
C
OH
HHO
H
C
C
O-O
C
OHH
CH2O
OHH
P
3NADP+
3NADPH + 3H+
3CO2
P
CH2OH
C
C
C
OHH
CH2O
OHH
O
P
P
P
P
C OH+ H
C
CH2O
OHH
C
H O
CH2OH
C
C
C
HHO
CH2O
OHH
O
P
P
Fruktozo 6-P
CH2OH
C
C
C
HHO
OHH
O
CH OH
CH2O
P
Fruktozo 6-P
CH2OH
C
C
C
HHO
OHH
O
CH OH
CH2O
C
C
CH2O
OH + H
HO
Gliceraldehid 3-P
P
Pentozofosfatni
put
![Page 55: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/55.jpg)
Oksidativna dekarboksilacija piruvata
E1: piruvat dekarboksilazaoksidativna dekarboksilacija piruvata
E2: dihidrolipoil transacetilazatransfer acetil grupe sa TPP na lipoicnu kiselinu
E3: dihidrolipoil dehidrogenazatransfer acetil grupe na CoA, transfer elektrona sa redukovane lipoicne kiseline na NADH
![Page 56: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/56.jpg)
TCA
![Page 57: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/57.jpg)
Aktivacija masnih
kiselina i
ulazak u
mitohondrije
![Page 58: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/58.jpg)
Acil-CoA
trans ∆2 enoil-CoA
β-Keto acil-CoA
acil-CoAdehidrogenaza
FAD
CH2 CH CH C SCoA
O
CH3
CH3 CH2 CH2 CH2 C SCoA
O
FADH2
CH3 CH2 CH CH2 C SCoA
OOH
CH3 CH2 CH CH2 C SCoA
OO
CH3 CH2 C SCoA +
O
C SCoA
O
CH3
β-keto tiolaza
β-hidrokis acil-CoAdehidrogenaza
enoil-CoA hidrataza
L−β-Hidroksi acil-CoA
Acil-CoA Acetil-CoA
NAD
NADH + H+
CoASH
β-Oksidacija H2O
Mitohondrijski matriks
C=n
C=n-2
Spiralni put
Elektron transportni lanac
Elektron transportni lanac
(2C atoma kraci)'
Oksidacija
masnih kiselina
![Page 59: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/59.jpg)
![Page 60: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/60.jpg)
Aceton Acetoacetat ββββ-Hidroksibutirat
Neenzimskareakcija
C
O
CH2
CH3
COO-
CH3
C
CH3
O HC
CH2
COO-
CH3
OH
CO2
β-hidroksibutiratdehidrogenaza
NADH + H+ NAD+
Ketonska tela
![Page 61: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/61.jpg)
C SCoA +
O
CH3 C SCoA
O
CH3
C
SCoA
O
CH2
C
OH
CH2CH3 C
O
O-
2 Acetil-CoA
CH CH2CH3 C
O
O-
O
CH CH2CH3 C
O
O-
OH
C CH3CH3
O
Acetoacetil-CoA
ββββ-Hidroksi-ββββ-metilglutaril-CoA (HMG-CoA)
Acetoacetat
Aceton D-ββββ-Hidroksibutirat
HMG-CoA sintaza
HMG-CoA liaza
D-β-hidroksibutirat dehidrogenaza
tiolazaCoA-SH
Co-ASH
C SCoA
O
CH3
SpontanoNADH + H+
NAD+
Acetil-CoA
C
O
CH2
CH3
C
SCoA
O
CO2
Ketogeneza
![Page 62: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/62.jpg)
C
O
CH2
CH3
COO-
HC
CH2
COO-
CH3
OH β-hidroksibutirat
dehidrogenaza
NAD+
Sukcinat
ββββ-Hidroksibutirat
NADH + H+
Acetoacetat
Acetoacetil-Co-A
Sukcinil-Co-A
β-ketoacil-Co-A transferaza
Acetil-Co-A Acetil-Co-A
Krebsov ciklus
Koriscenje ketonskih tela
![Page 63: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/63.jpg)
Malat-aspartat šatl
![Page 64: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/64.jpg)
Glicerol 3-fosfat
šatl
![Page 65: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/65.jpg)
Elektron transportni lanac i oksidativna fosforilacija
![Page 66: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/66.jpg)
Deo energije
gradijenta
koncentracije H+ jona
se koristi za
generisanje toplote
![Page 67: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/67.jpg)
Metabolizam aminokiselina
![Page 68: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/68.jpg)
Glukogene aminokiseline
![Page 69: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/69.jpg)
Ketogene aminokiseline
![Page 70: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/70.jpg)
transaminaza
Amino kiselina1 α-Ketokiselina1
α-Ketokiselina2 Amino kiselina2
αααα-Ketoglutarat Glutamat
aspartattransaminaza
(AST)
Aspartat Oksalacetat
COO-
C
CH2
O
COO-
COO-
C
CH2
O
CH2
COO-
COO-
C
CH2
COO-
HH3N+
COO-
C
CH2
CH2
COO-
HH3N+
Transaminacija
![Page 71: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/71.jpg)
Oksidativna deaminacija glutamata
![Page 72: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/72.jpg)
Sinteza karbamoil fosfata
![Page 73: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/73.jpg)
Citosol
Mitohondrija
CH2
C
CH2
CH2NH2
COOH
NH2H
CH2
C
CH2
CH2
COOH
NH2H
NH
C O
NH2
C O P O-H2N
OO
O -
CO2 + H2O
Pi
HCO3- + NH4
+
2 ATP
2 ADP + Pi
carbamoil fosfat sintaza I (CPSI)
ornitin transkarbamoilaza
Citrulin
Ornitin
Karbamoil fosfat
Urin
CH2
C
CH2
CH2NH2
COOH
NH2H
CH2
C
CH2
CH2
COOH
NH2H
NH
C O
NH2
Ornitin
Citrulin
Aspartat
Arginin
CH2
C
CH2
CH2
COOH
NH2H
NH
C NH
NH2
CH2
C
CH2
CH2
COOH
NH2H
NH
C NH
NH
CH
COOH
CH2
COOH
HC
CH
COOH
COOH
CH2
COOH
CH2N H
COOH
Argininosukcinat
Fumarat
ATP AMP + PPi
H2O
C O
NH2
NH2
Urea
arginaza
argininosukcinatliaza
argininosukcinatsintetaza
Ciklus uree
![Page 74: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/74.jpg)
Metabolizam
hema
![Page 75: Metabolizam i Regulacija](https://reader036.fdocument.pub/reader036/viewer/2022081719/557213e0497959fc0b933c87/html5/thumbnails/75.jpg)
Table 14-3
Metabolicka aktivnost u citosolu i mitohondrijama
_____________________________________________
organela glavne funkcije
_____________________________________________________________
Mitohondrije TCA, elektron transport i oksidativna fosforilacija, oksidacija masnih kiselina, razlaganje aminokiselina, sinteza karbamoil fosfata i deo ciklusa uree, oksidativna dekarboksilacija piruvata, ketogeneza
Citosol glikoliza, pentozofosfatni put, biosinteza masnih kiselina, vecina reakcija glukoneogeneze, sinteza i razlaganje glikogena, veci deo ciklusa uree