Katabolisme Lipid

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Biokimia Jurusan Biologi FMIPA - UNDIP

Transcript of Katabolisme Lipid

Page 1: Katabolisme Lipid

Biokimia

Jurusan Biologi

FMIPA - UNDIP

Page 2: Katabolisme Lipid

ASAMLEMAK

GLISEROLALBUMIN

DARAH

DIHIDROKSIASETON FOSFAT

GLIKOLISIS

Gliserol kinaseGliserol fosfat dehidrogenase

Page 3: Katabolisme Lipid

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

Page 4: Katabolisme Lipid

-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

Page 5: Katabolisme Lipid

-OKSIDASI ASAM LEMAK

Page 6: Katabolisme Lipid

-Oxidationpathway inmatrix

Fatty acyl-CoA formed in cytosol by enzymesof outer mitochondrial membrane & ER

Mitochondrion

Page 7: Katabolisme Lipid

AKTIVASI ASIL - KoA

• Asil-KoA sintase (tiokinase) pd retikulum endoplasma & di luar membran mitronondria

• ATP

• Terjadi pada dua langkah

melibatkan

Page 8: Katabolisme Lipid

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

Page 9: Katabolisme Lipid

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

Page 10: Katabolisme Lipid

ASIL LEMAK KARNITIN

Asil lemak – KoA tidak dapat menembus membran dalam mitokondria

KARNITIN

Page 11: Katabolisme Lipid

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

Page 12: Katabolisme Lipid

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

Page 13: Katabolisme Lipid

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

Page 14: Katabolisme Lipid

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

Page 15: Katabolisme Lipid

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

Page 16: Katabolisme Lipid

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

Page 17: Katabolisme Lipid

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.

Page 18: Katabolisme Lipid

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

Page 19: Katabolisme Lipid

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

Page 20: Katabolisme Lipid

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

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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

Page 22: Katabolisme Lipid

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

Page 23: Katabolisme Lipid

H C CH3 C S KoA O

COO-

D-Metilmalonil-KoA

CH3 C H C S KoA O

COO-

Metilmalonil epimerase

L-Metilmalonil-KoA

Page 24: Katabolisme Lipid

CH3 C H C S KoA O

COO-

L-Metilmalonil-KoA

CH2

CH2

CH2 S KoA O

COO-

Suksinil-KoA

Metilmalonil KoA mutase

Page 25: Katabolisme Lipid

Glucose-6-phosphatase glucose-6-P glucose

Gluconeogenesis Glycolysis

pyruvate fatty acids

acetyl CoA ketone bodies cholesterol oxaloacetate citrate

Krebs Cycle

Page 26: Katabolisme Lipid

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