lipidi metabolizam
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Transcript of lipidi metabolizam
![Page 1: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/1.jpg)
V. Metabolizam LipidaA. Probava, apsorbcija i raspodjela B. Mobilizacija uskladištenih triacilglicerola
C. Metabolizam masnih kiselina
1. Oksidacijaa. Energetika
b. Keto-tijela
2. Biosinteza
![Page 2: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/2.jpg)
V. Metabolizam LipidaA. Probava, apsorbcija i raspodjela B. Mobilizacija uskladištenih triacilglicerola
C. Metabolizam masnih kiselina
1. Oksidacijaa. Energetika
b. Keto-tijela
2. Biosinteza
![Page 3: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/3.jpg)
Emulgiranje
Hidroliza
TG
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Re-esterifikacijaMukoza
crijeva
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Hilomikroni
Emulgator
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Lipoprotein lipaza
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V. Metabolizam LipidaA. Probava, apsorbcija i raspodjela B. Mobilizacija uskladištenih triacilglicerola
C. Metabolizam masnih kiselina
1. Oksidacijaa. Energetika
b. Keto-tijela
2. Biosinteza
![Page 8: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/8.jpg)
Lipaza adipoznog tkiva (ATL)
G protein regulira porast cAMP
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V. Metabolizam LipidaA. Probava, apsorbcija i raspodjela B. Mobilizacija uskladištenih triacilglicerola
C. Metabolizam masnih kiselina
1. Oksidacijaa. Energetika
b. Keto-tijela
2. Biosinteza
![Page 10: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/10.jpg)
V. Metabolizam LipidaA. Probava, apsorbcija i raspodjela B. Mobilizacija uskladištenih triacilglicerola
C. Metabolizam masnih kiselina
1. Oksidacijaa. Energetika
b. Keto-tijela
2. Biosinteza
![Page 11: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/11.jpg)
R
O
OH
CoASH ATP
AMP + PPi
R
O
S CoA
R
O
S CoA
Inner Mitochondrial Membrane Carnitine Transporter
Cytosol Side
Matrix Side
Fatty Acid
Fatty Acyl CoA
Fatty Acyl CoA
FAD
FADH2
ETS2 ATP
R
O
S CoAalpha-beta unsat.Fatty Acyl CoA
H2O
R
O
S CoA
OH
R
O
S CoA
NAD
NADH + HETS
3 ATP
O
CoA-SH
R
O
S CoA H3C
O
S CoA
Beta-hydroxy-Fatty Acyl CoA
(trans)
Beta-keto-Fatty Acyl CoA
Thiolase
Kreb'sCycle
+
Fatty Acyl CoA Acetyl CoA
Aktivacija i unos u mitohondrije
acil CoA sintetaza2 Pi
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R
O
S CoA
Inner Mitochondrial Membrane Carnitine Transporter
Matrix Side
Fatty Acyl CoA
FAD
FADH2
ETS2 ATP
R
O
S CoAalpha-beta unsat.Fatty Acyl CoA
H2O
R
O
S CoA
OH
R
O
S CoA
NAD
NADH + HETS
3 ATP
O
CoA-SH
R
O
S CoA H3C
O
S CoA
Beta-hydroxy-Fatty Acyl CoA
(trans)
Beta-keto-Fatty Acyl CoA
Thiolase
Kreb'sCycle
+
Fatty Acyl CoA Acetyl CoA
oksidacija
Hidratacija
oksidacija
Tiolitičko cjepanje
1
2
3
4
H van
H2O ulazi
H van
Cjepanje
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V. Metabolizam LipidaA. Probava, apsorbcija i raspodjela B. Mobilizacija uskladištenih triacilglicerola
C. Metabolizam masnih kiselina
1. Oksidacijaa. Energetika
b. Keto-tijela
2. Biosinteza
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Energetika oksidacije
H3C S
O
CoA
acetyl CoA
FADH2
NADH
H3C OH
O
ETS
ETS
___ ATP
___ ATP
TCA
ETS____ ATP
_____ ATP per cycle
- 2 ATP for activation
23
12
17
17171712
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V. Metabolizam LipidaA. Probava, apsorbcija i raspodjela B. Mobilizacija uskladištenih triacilglicerola
C. Metabolizam masnih kiselina
1. Oksidacijaa. Energetika
b. Keto-tijela
2. Biosinteza
![Page 16: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/16.jpg)
Problemi koji vode stvaranju keto-tijela fatty acids
To the blood
glucose
acetyl CoA
TCACycle
OAA
Kod dijabetesa i gladovanja, u jetri se odvija glukoneogeneza
Izvor energije za jetru
Keto-tijela
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H3C SCoA H3C C
H2
O
H3C SCoA
OO
S
O
CoA
acetoacetyl CoA
H3C SCoA
O
OOC
CH2
CH2
S
OOH
CH3
CoASH
CoA
hydroxy-methyl-glutaryl CoA (HMG CoA)
H3C SCoA
O
OOC
CH2
C
CH3
O
acetoacetate
CO2
H3C
C
CH3
O
acetone
OOC
CH2
CH
CH3
OHNADH NAD+
-hydroxybutyrate
cholesterol
CoASH
+Thiolase
KETONE BODIES
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2. Biosinteza masnih kiselina
a. Nastajanje Malonil-CoA
b. Sintaza masnih kiselina
c. Reakcije
d. Nezasićene masne kiseline
e. Eikozanoidi
D. Biosinteza triacilglicerola i fosfolipida
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Piruvat karboksilaza
Piruvat dehidrogenaza
Kada je potreba za energijom zadovoljena, citrat se usmjerava u citoplazmu
Inducira Inzulin
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H3C C
O
H3C CH2 CH2 C
O
H3C CH2 CH2 CH2 CH2 C
O
malonyl CoA malonyl CoA
acetyl CoA acetyl CoA
Dodavanje acetila na karboksi kraj
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2. Biosinteza
a. Nastajanje Malonil-CoA
b. Sintaza masnih kiselina
c. Reakcije
d. Nezasićene masne kiseline
e. Eikozanoidi
D. Biosinteza triacilglicerola i fosfolipida
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Nastajanje Malonil CoA
H3C SCoA
OCO2
Biotin
ATP
acetyl CoAcarboxylase ADP + Pi
CH2
SCoA
O
OOC
acetyl CoA malonyl CoA
Slično karboksilaciji piruvata u glukoneogenezi
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2. Biosinteza
a. Nastajanje Malonil-CoA
b. Sintaza masnih kiselina
c. Reakcije
d. Nezasićene masne kiseline
e. Eikozanoidi
D. Biosinteza triacilglicerola i fosfolipida
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Dimer
12
Svaka podjedinica ima 7 katalitičkih domena
Svaka podjedinica ima 2
SH-skupine
Cisteinski ostaci
Pantotein
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2. Biosinteza
a. Nastajanje Malonil-CoA
b. Sintaza masnih kiselina
c. Reakcije
d. Nezasićene masne kiseline
e. Eikozanoidi
D. Biosinteza triacilglicerola i fosfolipida
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1 Dodatak malonila na SH pantoteina iz ACP-a
2 Kondenzacija malonila s acilom na cys-SH
3 Redukcija keto u hidroksi skupinu
4 Dehidratacija stvara dvostruku vezu
5 Redukcija dvostruke veze
Pomak na cys-SH skupinu
CoASHCoASH
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SC
O
H3C
SC
OCH3
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SC
OCH3
SC
O
H3C
SC
OC
O
-O
SC
O
C
O
O-
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SC
OCH3
SC
O
H3C
SC
H2C O
SC
OCH2
CO2
CO2
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SC
O
C
O
CH3
SC
OC
O
H3C
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SC
OCH
HO
H3C
SC
O
CHCH3
OH
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SC
OH3C
SC
O CH3
H2O
H2O
![Page 33: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/33.jpg)
SC
OH3C
SC
O CH3
![Page 34: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/34.jpg)
SC
O CH3
SC
OH3C
Sljedeći malonil
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2. Biosinteza
a. Nastajanje Malonil-CoA
b. Sintaza masnih kiselina
c. Reakcije
d. Nezasićene masne kiseline
e. Eikozanoidi
D. Biosinteza triacilglicerola i fosfolipida
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Sinteza nezasićenih masnih kiselina
SATURATED FATTY ACIDS
palmitic acid (16:0) palmitoleic acid (16:19)DS
UNSATURATED FATTY ACIDS
stearic acid (18:0)DS
oleic acid (18:19)
DS
?18:26,
9
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2. Biosinteza
a. Nastajanje Malonil-CoA
b. Sintaza masnih kiselina
c. Reakcije
d. Nezasićene masne kiseline
e. Eikozanoidi
D. Biosinteza triacilglicerola i fosfolipida
![Page 38: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/38.jpg)
Diet
Linoleic acid18:29,12
Desaturase
18:39,12
Add 2 carbons
COOH
CH3
CH3
PG1 SeriesTX1 SeriesLT3 SeriesDesaturase
COOH
eicosatrienoic acid
20:3
eicosatetraenoic acid20:4
PG2 SeriesTX2 SeriesLT4 Series
Diet
Linolenic acid18:39,12,15
Desaturase
18:49,12,15
Add 2 carbons
COOH
Desaturase
eicosatetraenoic acid
20:4
CH3
eicosapentaenoic acid
20:5
CH3
COOH
PG3 SeriesTX3 SeriesLT5 Series
8
1114
5
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Dietary Essential Fatty Acids (linoleic acid)
Arachidonic Acid
CH2
CH
CH
O
O
O P O Choline
C
O
R1
arachidonic acid
phospholipase A2 Glucocorticosteroids
COOH
CH3
Arachidonic Acid
Membrane Phosphoacylglycerol
Prostaglandins Thromboxanes Leukotrienes
Inhibicija glukokortikosteroidima
![Page 40: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/40.jpg)
COOH
CH3
Arachidonic Acid
O
O
O2
NSAIDS
![Page 41: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/41.jpg)
O2
![Page 42: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/42.jpg)
2. Biosinteza
a. Nastajanje Malonil-CoA
b. Sintaza masnih kiselina
c. Reakcije
d. Nezasićene masne kiseline
e. Eikozanoidi
D. Biosinteza triacilglicerola i fosfolipida
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Izvor Glicerol-3-fosfata
LiverLiver and Adipose Tissues
Glycerol-3-PGlycerol DHAP Glucose
ATP ADP NAD+ NADH + H+
glycerol kinaseFA1CoA
FA2CoA
CoASH
CoASH
O C
O
R1
OC
O
R2
O P2-
Phosphatidic acid
1
2
![Page 44: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/44.jpg)
O C
O
R1
OC
O
R2
O P2-
Phosphatidic acid
O C
O
R1
OC
O
R2
O
PPi CTP
PO
PO
cytidine
O C
O
R1
OC
O
R2
O PO
head group
HO head group
CMP
H2O
Pi
O C
O
R1
OC
O
R2
OH
Diacylglycerol
head groupHO
O P O P O
CTP
Pi
head group cytidine
O C
O
R1
OC
O
R2
O PO
head group
FA3CoA
CoASH
O C
O
R1
OC
O
R2
O C
O
R3
Triacylglycerol
Store in Adipose Tissue
Liver
Transport in the Blood
CMP
![Page 45: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/45.jpg)
2. Biosinteza
a. Nastajanje Malonil-CoA
b. Sintaza masnih kiselina
c. Reakcije
d. Nezasićene masne kiseline
e. Eikozanoidi
D. Biosinteza triacilglicerola i fosfolipida
E. REGULACIJA
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Glucose
Glucose
G-6-P
F-1,6-BP
glyceraldehyde-3-P DHAP
pyruvate
pyruvate
OAA acetyl CoA
citrate citrate
OAA
acetyl CoA
malate
NADPH NADP+
PPP
NADP+
NADPH
malonyl CoA
ACC
Fatty acidsynthase
Fatty acyl CoA
Fatty Acids
Glycerol-3-P
TG
LIVER OR ADIPOSE CELL
malic enzyme
* Inducira inzulin
*
**
*
*
*
*
![Page 47: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/47.jpg)
Pi
Stimulira inzulin
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F. Kolesterol 1. Biosinteza2. Regulacija3. Uloga
a. Steroidni hormonib. Žučne soli
G. Transport Lipida 1. Podjela lipoproteina2. Specifična uloga transporta3. Metabolizam lipoproteina4. Hiperlipoproteinemije
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F. Kolesterol 1. Biosinteza2. Regulacija3. Uloga
a. Steroidni hormonib. Žučne soli
G. Transport Lipida 1. Podjela lipoproteina2. Specifična uloga transporta3. Metabolizam lipoproteina4. Hiperlipoproteinemije
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H3C SCoA H3C C
H2
O
H3C SCoA
OO
S
O
CoA
acetyacetyl CoA
H3C SCoA
O
OOC
CH2
CH2
S
OOH
CH3
CoASH
CoA
CoASH
+Thiolase
OOC
CH2
CH2
CH2
OH
CH3
OH NADPH
NADP+
NADPH
NADP+
HMG CoA HMG CoA Reductase
mevalonic acid
CoASH
Keto-tijela
HH
![Page 51: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/51.jpg)
OOC
CH2
CH2
CH2
OH
CH3
OH
mevalonic acid
OOC
CH2
CH2
CH2
O
CH3
O
3 ATP
3 ADP
P
P O PPi
H2C CH2
CH2 O P O P
CH3CO2
H3C CH
CH2 O P O P
CH3
H2C CH2
CH2 O P O P
CH3
+
isopentenyl pyrophosphate
dimethylallyl pyrophosphate isopentenyl pyrophosphate
Isomerization
![Page 52: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/52.jpg)
Reakcije polimerizacije
H3C CH
CH2 O P O P
CH3
H2C CH2
CH2 O P O P
CH3
+
dimethylallyl pyrophosphate isopentenyl pyrophosphate
PPi
O P O P
Geranyl pyrophosphate
Monoterpenes
a
b
c
2 Pi
(C10)
![Page 53: lipidi metabolizam](https://reader033.fdocuments.net/reader033/viewer/2022061113/545e5970af795935708b482f/html5/thumbnails/53.jpg)
O P O P
Geranyl pyrophosphate
PPi
isopentenyl pyrophosphate
O P O P
Sesquiterpenes
Diterpenes (C20)
(C15)
IPP
PPi
Farnesyl pyrophosphate
Dodatak IPP
(C15)
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Kondenzacija u skvalen
O P O P
Farnesyl pyrophosphate
2 PPi
NADPH
NADP+
Squalene (C30)
*
**
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Ciklizacija i pretvorba lanosterola u kolesterol
HO HO
Squalene
CholesterolLanosterol
1)
3)
2)
(C30)
A B
C D
O2
NADPHNADP+O
H2O
Izlaze 3 metilne grupePomak = veze
Redukcija = u pobočnom lancu
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F. Kolesterol 1. Biosinteza2. Regulacija3. Uloga
a. Steroidni hormonib. Žučne soli
G. Transport Lipida 1. Podjela lipoproteina2. Specifična uloga transporta3. Metabolizam lipoproteina4. Hiperlipoproteinemije
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H3C SCoA H3C C
H2
O
H3C SCoA
OO
S
O
CoA
acetyacetyl CoA
H3C SCoA
O
OOC
CH2
CH2
S
OOH
CH3
CoASH
CoA
CoASH
+Thiolase
OOC
CH2
CH2
CH2
OH
CH3
OH NADPH
NADP+
NADPH
NADP+
HMG CoA HMG CoA Reductase
mevalonic acid
CoASH
HH
Inducira inzulin
Aktivnost je regulirana fosforilacijomdefosforilacijom
Glucagon fosforilacijom gubi na aktivnosti
Insulin stimulira fosfataze koje povisuju aktivnost
Kolesterol inhibira aktivnost
Aktivnost inhibiraju i statini (lovastatin, pravastatin, itd.)
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F. Kolesterol 1. Biosinteza2. Regulacija3. Uloga
a. Steroidni hormonib. Žučne soli
G. Transport Lipida 1. Podjela lipoproteina2. Specifična uloga transporta3. Metabolizam lipoproteina4. Hiperlipoproteinemije
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Kolesterol
Vitamin DUV
Steroidni hormoniglukokortikosteroidi
spolni hormoni
Žučne soli
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F. Kolesterol 1. Biosinteza2. Regulacija3. Uloga
a. Steroidni hormonib. Žučne soli
G. Transport Lipida 1. Podjela lipoproteina2. Specifična uloga transporta3. Metabolizam lipoproteina4. Hiperlipoproteinemije
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Hipofiza
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F. Kolesterol 1. Biosinteza2. Regulacija3. Uloga
a. Steroidni hormonib. Žučne soli
G. Transport Lipida 1. Podjela lipoproteina2. Specifična uloga transporta3. Metabolizam lipoproteina4. Hiperlipoproteinemije
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Metabolizam žučnih soli
Vlakna iz prehrane
Lijekovi: smole ionski izmjenjivači (kolestiramin)
Kolesterol u krvi
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Sinteza kolne kiseline
OHHO HO
OHHOOHHO
OH
COOH
OHHO
COOH
OHHO
OH
O2 H2O
XH2 X
Reduction of DBEpimerization of OH at C3 to
Hydroxylation
7
7
12
7
3
33
Removal of 3 carbons from sidechain and oxidation to COOH
12
73 73
Cholic acid Chenodeoxycholic acid
CholesterolHydroxylation
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COOH
OHHO
COOH
OHHO
C
OHHO
OH
OH
H2N COOH
12
73
C
OHHO
OH
12
73
CH3
CH3 C
OHHO73
C
OHHO73
12
73 73
Cholic acid Chenodeoxycholic acid
H2NSO3H
glycinetaurine
O
HN COOH
O
O
O
HN
HN COOH
SO3H HN SO3H
Glycocholic acid
Taurocholic acid
Glycochenodeoxycholic acid
Taurochenodeoxycholic acid
H2N COOH
glycine
H2NSO3H
taurine
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F. Kolesterol 1. Biosinteza2. Regulacija3. Uloga
a. Steroidni hormonib. Žučne soli
G. Transport Lipida 1. Podjela lipoproteina2. Specifična uloga transporta3. Metabolizam lipoproteina4. Hiperlipoproteinemije
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F. Kolesterol 1. Biosinteza2. Regulacija3. Uloga
a. Steroidni hormonib. Žučne soli
G. Transport Lipida 1. Podjela lipoproteina2. Specifična uloga transporta3. Metabolizam lipoproteina4. Hiperlipoproteinemije
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Lipoproteini
TG
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Sastav lipoproteina
CLASS DENSITY PERCENTPROTEIN
PERCENT LIPID
TG PL CHOL &ESTERS
FFA
Chylomicrons < 0.96 2 98 85 8 3 0
VLDL 0.96-1.006 9 91 55 20 17 1
IDL 1.006-1.019 11 89 26 23 38 1
LDL 1.019-1.063 20 80 10 20 45 1
HDL 1.063-1.210 45 55 8 25 20 0
Albumin-FFA > 1.280 99 1 0 0 0 100
PERCENT OF TOTAL WEIGHT
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F. Kolesterol 1. Biosinteza2. Regulacija3. Uloga
a. Steroidni hormonib. Žučne soli
G. Transport Lipida 1. Podjela lipoproteina2. Specifična uloga transporta3. Metabolizam lipoproteina4. Hiperlipoproteinemije
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F. Kolesterol 1. Biosinteza2. Regulacija3. Uloga
a. Steroidni hormonib. Žučne soli
G. Transport Lipida 1. Podjela lipoproteina2. Specifična uloga transporta3. Metabolizam lipoproteina4. Hiperlipoproteinemije
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Lipoprotein lipase
HDL nosi apoproteine
HDL nosi apoproteine
Apo CII aktivira LPL
Endocitoza putem receptora
Endocitoza putem receptora
TG se uklanjaju u jetri
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Unos LDL-a u stanice na periferiji
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Metabolizam HDL-a
HDL
ApoCII
ApoE
Nascent chylomicron
Chylomicron
Nascent VLDL
VLDL
HDL
HDLC
ExtrahepaticTissues
C
LIVER
To LDL
C
Cchylomicronand VLDL remnants
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F. Kolesterol 1. Biosinteza2. Regulacija3. Uloga
a. Steroidni hormonib. Žučne soli
G. Transport Lipida 1. Podjela lipoproteina2. Specifična uloga transporta3. Metabolizam lipoproteina4. Hiperlipoproteinemije
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Hiperlipoproteinemije
TYPE ELEVATEDLIPOPROTEIN(S)
MAJOR LIPID(S) ELEVATED
RELATIVE INCIDENCE
I chylomicrons triglycerides rare
IIa LDL cholesterol common
IIb LDL & VLDL chol & TG common
III IDL chol & TG uncommon
IV VLDL triglycerides common
V chylomicrons & VLDL triglycerides uncommon
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LDL i Ateroskleroza