Katabolisme Lipid
Transcript of Katabolisme Lipid
Biokimia
Jurusan Biologi
FMIPA - UNDIP
ASAMLEMAK
GLISEROLALBUMIN
DARAH
DIHIDROKSIASETON FOSFAT
GLIKOLISIS
Gliserol kinaseGliserol fosfat dehidrogenase
KATABOLISME GLISEROL
g l y c e r o l g l y c e r o l - 3 - P d i h y d r o x y a c e t o n e - P
C H 2
C H
C H 2
O H
H O
O PO 3
C H 2
C H
C H 2
O H
H O
O H
C H 2
C
C H 2
O H
O PO 3
O
A T P A D P H + +N A D + N A D H
1 2
-OKSIDASI ASAM LEMAK
• Asam lemak – as lemak dipecah dlm matriks mitokondria via -oksidasi asam lemak
• Tahap pemecahan melibatkan multienzim, terutama as lemak rantai panjang
• Tahap awal pemecahan as lemak harus diaktivasi dlm bentuk asil-KoA
-OKSIDASI ASAM LEMAK
-Oxidationpathway inmatrix
Fatty acyl-CoA formed in cytosol by enzymesof outer mitochondrial membrane & ER
Mitochondrion
AKTIVASI ASIL - KoA
• Asil-KoA sintase (tiokinase) pd retikulum endoplasma & di luar membran mitronondria
• ATP
• Terjadi pada dua langkah
melibatkan
Fatty acid activation
N
NN
N
NH2
O
OHOH
HH
H
CH2
H
OPOPOP O
O
O O
O O
O
N
NN
N
NH2
O
OHOH
HH
H
CH2
H
OPOC
O
O
R
O
SCR
O
CoA
R C
O
O
PPi
CoA SH
AMP
2 Pi
fatty acid
ATP
acyl- adenylate
acyl-CoA
Summary of fatty acid activation:
fatty acid + ATP acyladenylate + PPi
PPi 2 Pi
acyladenylate + HS-CoA acyl-CoA + AMP
Overall: fatty acid + ATP + HS-CoA acyl-CoA + AMP + 2 Pi
ASIL LEMAK KARNITIN
Asil lemak – KoA tidak dapat menembus membran dalam mitokondria
KARNITIN
H3C N CH2 CH CH2
CH3
CH3
OH
COO+
R
C
SCoA
O+
H3C N CH2 CH CH2
CH3
CH3
O
COO+
C
R
O
+ HSCoA
carnitine
fatty acyl carnitine
Carnitine Palmitoyl Transferase
cytosol mitochondrial matrix O O
R-C-SCoA HO-carnitine HO-carnitine R-C-SCoA HSCoA R-C-O-carnitine R-C-O-carnitine HSCoA
O O
1 2
3
OKSIDASI ASAM LEMAK JENUH
H3C(CH2)nCCCSCoA
H
H
H
HO
123
H3C(CH2)nCCCSCoA
H
HO
H3C(CH2)nCCH2CSCoA
OH
O
H2O
FADH2
FAD
H
H3C(CH2)nCCH2CSCoA
OO
H+ + NADH
NAD+
CH3CSCoA
O
H3C(CH2)nCSCoA +
O
HSCoA
fatty acyl-CoA
trans-2-enoyl-CoA
Acyl-CoA Dehydrogenase
LANGKAH I
H3C (CH2)n C C C SCoA
H
H
H
H O
123
H3C (CH2)n C C C SCoA
H
H O
H3C (CH2)n C CH2 C SCoA
OH
O
H2O
FADH2
FAD
H
H3C (CH2)n C CH2 C SCoA
OO
H+ + NADH
NAD+
CH3 C SCoA
O
H3C (CH2)n C SCoA +
O
HSCoA
fatty acyl-CoA
trans-2-enoyl-CoA
3-L-hydroxyacyl-CoA
Acyl-CoA Dehydrogenase
Enoyl-CoA Hydratase
LANGKAH II
H3C (CH2)n C C C SCoA
H
H
H
H O
123
H3C (CH2)n C C C SCoA
H
H O
H3C (CH2)n C CH2 C SCoA
OH
O
H2O
FADH2
FAD
H
H3C (CH2)n C CH2 C SCoA
OO
H+ + NADH
NAD+
CH3 C SCoA
O
H3C (CH2)n C SCoA +
O
HSCoA
3-L-hydroxyacyl-CoA
-ketoacyl-CoA
fatty acyl-CoA acetyl-CoA (2 C shorter)
Hydroxyacyl-CoA Dehydrogenase
-Ketothiolase
LANGKAH III
H3C (CH2)n C CH2 C SCoA
OO
CH3 C SCoA
O
H3C (CH2)n C SCoA +
O
HSCoA-ketoacyl-CoA
fatty acyl-CoA acetyl-CoA (2 C shorter)
-Ketothiolase
LANGKAH IV
Summary of one round of the -oxidation pathway:
fatty acyl-CoA + FAD + NAD+ + HS-CoA
fatty acyl-CoA (2 C less) + FADH2 +
NADH + H+ + acetyl-CoA
The -oxidation pathway is cyclic.
OKSIDASI ASAM LEMAK TIDAK JENUH
C
O
S KoA
C
O
S KoA + 3 asetil KoA
Oleil-KoA(rantai 18 karbon)
Sis – Δ3-Enoil-KoA(rantai 12 karbon)
C
O
S
trans – Δ2-Enoil-KoA
KoA
Enoil-KoA Isomerase
C
O
S3–Hidroksiasil-KoA
KoA
C
O
S
trans – Δ2-Enoil-KoA
KoA
OH
enoil-KoA hidratase
MASUK SIKLUS SEPERTI PADA OKSIDASI ASAM LEMAK JENUH
H2O
OKSIDASI ASAM LINOLEAT
R CH2 C C C S KoA
O
H H
enoil-KoA hidratase Sis – Δ3-Enoil-KoA
R CH2 C CH2 C S KoA
O
OH
H
3-hidroksiasil-KoAepimerase D-3-Hidroksiasil-KoA
R CH2 C CH2 C S KoA
O
OH
H
3-hidroksiasil-KoAepimerase D-3-Hidroksiasil-KoA
R CH2 C CH2 C S KoA
O
H
OH
L-3-Hidroksiasil-KoA
MASUK SIKLUS SEPERTI PADA OKSIDASI ASAM LEMAK JENUH
OKSIDASI ASAM LEMAK BERKARBON GANJIL
CH2 CH2 C S KoA O
HCO3
ATP
AMP + PPi + H+
Propionil – KoA karboksilase
Propionil-KoA
H C CH3 C S KoA O
COO-
D-Metilmalonil-KoA
H C CH3 C S KoA O
COO-
D-Metilmalonil-KoA
CH3 C H C S KoA O
COO-
Metilmalonil epimerase
L-Metilmalonil-KoA
CH3 C H C S KoA O
COO-
L-Metilmalonil-KoA
CH2
CH2
CH2 S KoA O
COO-
Suksinil-KoA
Metilmalonil KoA mutase
Glucose-6-phosphatase glucose-6-P glucose
Gluconeogenesis Glycolysis
pyruvate fatty acids
acetyl CoA ketone bodies cholesterol oxaloacetate citrate
Krebs Cycle
H3C CH2C C
O O
SCoA
H3C C
O
SCoA
HSCoA
H2C C
H2C C
OH O
SCoA
CH3
C
O
O
H3C C
O
SCoA + H3C C
O
SCoA
HSCoA
O CH2C C
O O
CH3 H3C C
O
SCoA+
acetyl-CoA acetyl-CoA
acetoacetyl-CoA
acetyl-CoA
HMG-CoA
acetoacetate acetyl-CoA
Thiolase
HMG-CoA Synthase
HMG-CoA Lyase