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METABOLISME LIPID

Muntholib
Jurusan Kimia Fmipa
Universitas Negeri Malang
Pengertian Lipid
Biomolekul yang tidak larut dalam pelarut polar,
tetapi larut dalam pelarut organik
Tiga Macam Lipid:
 Triglycerides (triasilgliserol atau lemak)
 made of 3 fatty acids (fa) & 1 glycerol
 Fatty acids 4-22 Carbons long; mostly 16-20
 95% of dietary lipids (fats & oils)
 Phospholipids
 1 fatty acid replaced by a phosphate group atau
turunannya
 Sterols (Kolesterol dan turunannya)
 complex ringed structures; noncaloric
 ex. cholesterol & Vit D
Fungsi Lemak
 Concentrated energy (diet and main storage
form)
 Provides essential fatty acids (linoleic;
linolenic)
 Carrier of Fat Soluble Vits (A,D,E,K)
 Body Insulation & padding around organs
 Cell membranes
 Adds flavor & texture to foods
 Contributes to satiety (more than satisfy)
Metabolisme LIPID
Metabolisme LIPID
 Degradasi Lipid  Oksidasi asam lemak
 Pencernaan, penyerapan dan transpot lemak
 -oksidasi asam lemak

 Biosintesis Lipid
 Biosintesis asam lemak
 Biosintesis triasilgliserol
 Biosintesis fosfolipid
 Biosintesis kolesterol dan steroid
Pencernaan, Penyerapan, &
Transport Lemak
 Penggunaan lemak sebagai sumber energi
berhubungan erat dengan metabolisme
lipoprotein dan kolesterol.
 Mammal mempunyai 5 – 25% lipid dan 90% dlm
bentuk lemak (TAG) yg disimpan di dalam
jaringan adipose
 Hewan  lemak disimpan dalam adiposit
 Tumbuhan  biji  untuk perkembangan embrio
Sources of Fatty Acid Fuel
Diet Fat Storage Cells

Endogenous
production

Energy
PENCERNAAN LIPID
 Masalah utama  tidak larut dalam air
 Lemak  diemulsi oleh garam empedu 
mudah dicerna & diserap
garam empedu disintesis oleh liver & disimpan
dalam empedu
 Transportasi  membentuk kompleks dengan
protein  lipoprotein
Garam empedu adalah garam dari atas asam empedu yang
merupakan turunan kolesterol
Garam empedu  bersifat amfifilik  mengemulsi lemak 
membentuk misel
Lemak  dipecah oleh lipase pankreas  asam lemak,
MAG, DAG
 Penyerapan oleh sel mukosa usus halus
 Asam lemak yg diserap  disintesis kembali
menjadi lemak dalam badan golgi dan retikulum
endoplasma sel mukosa usus halus
 TAG  masuk ke sistem limfa membentuk
kompleks dengan protein  chylomicrons
Gliserol hasil hidrolisis TAG : diubah menjadi
DHAP oleh enzim :
1 Glycerol Kinase
2 Glycerol Phosphate Dehydrogenase
DHAP kemudian masuk ke dalam daur
Glikolisis
 Chylomicron membawa TAG dari sel mukosa usus halus ke
organ lain seperti jantung, otot, dan jaringan lemak.
 TAG yang disintesis di dalam hati dibawa oleh VLDL ke
organ lain
 Di organ target  di kapiler  TAG akan dihidrolisis
menjadi gliserol dan asam lemak
 Asam lemak bebas diserap, sisanya dibawa oleh serum
albumin  ke sel lain
 Asam lemak yg telah masuk ke dalam sel
Diubah menjadi energi
Diubah menjadi TAG untuk disimpan di adiposa
LIPOPROTEINS
 Transport lipids
 mixture of protein and lipids
 Proteins & phospholipids are water soluble
 packaged so water soluble compounds /
groups on outside and insoluble on inside
 like homogenized milk
 Lipoproteins have different forms,
functions, & effect to CVD
Lipoproteins
 Lipoproteins are classified as:
 HDLs – high-density lipoproteins have more
protein content
 LDLs – low-density lipoproteins have a
considerable cholesterol component
 VLDLs – very low density lipoproteins are
mostly triglycerides
 Chylomicrons
Cholesterol

Figure 24.22
Lipoproteins
 The liver is the main source of VLDLs,
which transport triglycerides to peripheral
tissues (especially adipose)
 LDLs transport cholesterol to the
peripheral tissues and regulate cholesterol
synthesis
 HDLs transport excess cholesterol from
peripheral tissues to the liver
 Also serve the needs of steroid-producing
organs (ovaries and adrenal glands)
Lipoproteins
 High levels of HDL are thought to protect
against heart attack
 High levels of LDL, increase the risk of
heart attack
Low Density LP (LDL)
 remnant of VLDL after most TG removed
 very HIGH in Cholesterol
 major component of total blood cholesterol
 not always effectively cleared by liver so other
tissues remove including artery walls
 esp when cholesterol has been modified
 risk of “high blood cholesterol” is from LDL, i.e.,
increases risk of CVD
Levels of LP & CVD Risk
 HDL > 60 mg/dl = Low risk
 HDL < 35 mg/dl = High risk
 LDL/HDL ratio < 4 = Low risk
 men’s HDL run from high 30’s to high
40’s
 women’s from low 50’s to low 60’s
(estrogen effect)
β oksidasi

Mengapa beta-
oksidasi?
 Oksidasi FA  jalur metabolisme penghasil
energi utama pada hewan, bbrp protista,
dan beberapa bakteri

 Elektron dr proses oksidasi FA  melewati


rantai respirasi mitokondria 
menghasilkan ATP
(asetil-SCoA hasil oksidasi FA  dioksidasi
sempurna menjadi CO2 via siklus TCA  ATP
sintesis)

 Pada vertebrata  sebagian asetil-SCoA


hasil β oksidasi  diubah menjadi keton
tubuh di hati (larut dalam air) dan di
transpor ke otak dan jaringan lain pada saat
gula tidak tersedia untuk sintesis gula.


3 TAHAPAN REAKSI OKSIDASI FA
DALAM MITOKONDRIA
1. Oksidasi FA  molekul 2 C : asetil-
SCoA

2. Oksidasi asetil-SCoA  CO2 via siklus


TCA

3. Transfer elektron dari reducing


power ke rantai respirasi
mitokondrial
β-oksidasi
 setelah memasuki
sel  FA masuk ke
matriks mitokondria
 degradasi lebih
lanjut.

 FA diaktivasi dgn
enzim fatty acyl–
SCoA ligase atau
Acyl-SCoA synthase /
thiokinase
Untuk masuk ke dalam matrik mitokondria,
asam lemak yang sudah diaktivasi 
memerlukan karier  karnitin
- Karnitin asiltransferase I : membran luar
- Karnitin asiltransferase II : membran dalam
β oksidasi
 Terdiri dari 4 proses utama:
 Dehidrogenasi

 Hidratasi

 Dehidrogenasi

 Thiolisis

 Berapakah jumlah reaksi yang dibutuhkan untuk


menghidrolisis sempurna asam palmitat menjadi
asetil-SCoA?
Step 1 : dehidrogenasi / oksidasi

• Berperan pada pembentukan rantai ganda antara atom


C2 – C3.
• Mempunyai akseptor hidrogen FAD+.
• Antara asam lemak yg berbeda panjangnya beda
enzimnya,
Step2 : Hidratasi

• Mengkatalisis hidrasi trans


enoyl-SCoA
• Penambahan gugus hidroksi
pada C no. 3
• Enzim bersifat stereospesifik
• Menghasilkan 3-L-
hidroksiasil-SCo. A
Step 3 : dehidrogenasi

• Mengkatalisis oksidasi -OH pada C no. 3 / C β 


menjadi keton

• Akseptor elektronnya : NAD+


Step 4 : thiolisis

• β-Ketothiolase  mengkatalisis pemecahan ikatan


thioester.
• Acetyl-SCoA  dilepas dan tersisa asam lemak asil-
SCoA yang terhubung dgn thio sistein mll ikatan
tioester.
• Tiol HSCoA menggantikan cysteine thiol, menghasilkan
fatty acyl-SCoA (yang telah berkurang 2 C).
COMPLETE OXIDATION
Fatty Acids : 9 kcal/g
Carbohydrates : 4 kcal/g
Protein : 4 kcal/g
Masya Allah yang telah memilih lemak sebagai
senyawa penyimpan kelebihan energi tubuh.
Sekiranya pilihan itu jatuh pada karbohidrat atau
protein maka:
• Gadis sexy 20 tahun yang beratnya 48 kg akan
berubah menjadi 63 kg
• Ibu muda 30 tahun yang beratnya 60 kg akan
berubah minimal menjadi 78
• Ibu-ibu 40 tahun yang beratnya 70 kg akan
berubah menjadi minimal 92 kg. Wow … is big
beauty?!
REVIEW DEGRADASI ASAM LEMAK
 Asam lemak merupakan bentuk simpanan
energi metabolik yang paling efisien.

 TAG terbentuk dari 3 asam lemak dan


gliserol.

 TAG dihidrolisis oleh enzim lipase di dalam


usus halus menjadi asam lemak dan
gliserol.

 Asam lemak melewati dinding usus halus,


dan TAG kembali disintesis dan ditransport
di dalam darah dalam bentuk chylomicrons.

 Chylomicrons terikat pada sel lemak


(adipocytes) dan TAG didegradasi lagi
menjadi asam lemak dan gliserol.
 Asam lemak masuk sel adiposa kmdn
disintesis kembali mjd TAG dan disimpan.
 TAG di dalam adiposa didegradasi menjadi
asam lemak sebagai respon terhadap sinyal
hormon.
 Asam lemak bergabung dengan CoASH
terlebih dahulu sebelum didegradasi.
 Degradasi asam lemak menjadi asetil-SCoA
terjadi dalam matriks mitokondria.
 Karnitine membawa asam lemak rantai
panjang dari sitoplasma ke dalam mitokondria
untuk didegradasi
 4 urutan reaksi degradasi asam lemak adalah :
oxidation, hydration, oxidation, thiolysis.
Ketogenesis: Formation of
Ketone Bodies
Thiolase
2 CH3COSCoA CH3COCH2COSCoA CH3COSCoA

Acetoacetyl CoA

HMG CoA
Synthase

Several
Cholesterol steps OH
(in cytosol)
See Slide 78 HO2C-CH2-C-CH2COSCoA

CH3
(in liver: mitochon-
drial matrix) Ketogenesis -Hydroxy--methylglutaryl CoA
(HMG CoA)
Ketogenesis: Formation
of Ketone Bodies (Cont’d.)
OH
HMG CoA
HO2C-CH2-C-CH2COSCoA lyase
CH3COCH2CO2
- CH3COSCoA Acetoacetate
CH3
HMG CoA NADH + H+
Dehydrogenase - CO2
NAD+

OH
CH3COCH3
CH3CHCH2CO2
Acetone
-Hydroxybutyrate (volatile)

Ketone bodies are important sources


of energy, especially in starvation
Biosintesis Asam Lemak
 Tidak sepenuhnya merupakan
kebalikan dari degradasi asam lemak
 Enzim yang berbeda bekerja untuk
reaksi yang berlawanan :degradasi
vs biosintesis
 Sintesis Asam lemak  baik pada
eukariotik dan prokariotik sama pada
umumnya

 Biosintesis terdiri dari 3 langkah terpisah :


 Biosintesis asam lemak dari asetil CoA
 Pemanjangan rantai asam lemak
 Desaturasi

 Lokasi biosintesis:
Biosintesis FA  di sitosol,
elongasi  di mitokondria dan ER,
desaturasi di ER

 Biosintesis as lemak  membutuhkan


malonil-SCo A sebagai substrat
 Diperlukan ATP untuk sintesis
malonil-SCoA
 Reaksi biosintesis asam palmitat:
Dari 8 acetyl-CoAs diperlukan  7
ATPs +14 NADPHs

 Enzim sintesis merupakan ensim


komplek : fatty acid synthase yg
terdiri atas 8 rantai polipeptida
 Each malonyl group and acetyl (or longer acyl) group is
activated by a thioester that links it to fatty acid synthase, a
multienzyme system described later in the text.
 1 Condensation of an activated acyl group (an acetyl group
from acetyl-CoA is the first acyl group) and two carbons
derived from malonyl-CoA, with elimination of CO2 from the
malonyl group, extends the acyl chain by two carbons. The
mechanism of the first step of this reaction is given to
illustrate the role of decarboxylation in facilitating
condensation. The β-keto product of this condensation is then
reduced in three more steps nearly identical to the reactions
of β oxidation, but in the reverse sequence: 2 the β-keto
group is reduced to an alcohol, 3 elimination of H2O creates a
double bond, and 4 the double bond is reduced to form the
corresponding saturated fatty acyl group.
LANGKAH 1
 Sintesis malonyl-SCoA dari acetyl-
SCoA and HCO3-
 Dikatalisis oleh acetyl-SCoA
carboxylase dan memerlukan ATP
 Merupakan langkah awal sintesis
asam lemak yg sangat penting
 malonyl-SCoA dan acetyl-SCoA 
substrat enzim fatty acid synthase
complex.
LANGKAH 2 PERSIAPAN
1. Acetyl-SCoA + ACP-SH <=>
Acetyl-SACP + CoASH
(catalyzed by Acetyl-SCoA-ACP
Transacylase)
2. Malonyl-SCoA + ACP-SH <=>
Malonyl-SACP + CoASH
(catalyzed by Malonyl-SCoA-ACP
Transacylase
 Pada sintesis asam palmitat 
setelah butiril-SACP  siklus akan
berlanjut dari awal lagi sampai 7X
dan kemudian diakhiri dgn hidrolisis
yg memecah palmitat dengan ACP.
 Reaksi netto biosintesis palmitat :
Asetil CoA + 7 malonil CoA + 14
NADPH  palmitat + 7 CO2 + 14
NADP+ + 8 CoA-SH + 7 H2O
Cholesterol sources, biosynthesis
and degradation
 diet
 only found in animal fat
 biosynthesis
 primarily synthesized in the liver from acetyl CoA
 biosynthesis is inhibited by LDL uptake by the liver
 degradation
 only occurs in the liver
 cholesterol is converted to bile acids
Biosynthesis of cholesterol

- synthesis of acetoacetyl CoA


Biosynthesis of cholesterol

- synthesis of mevalonate

rate-limiting step
and step subject to
inhibition by statins
Biosynthesis of cholesterol

- synthesis of isopentenyl
- pyrophosphate

A monoterpene
Synthesis of farnesyl
pyroposphate
Biosintesis Kolesterol
Atherosclerosis
can occur in almost any artery in the
body

The body depends on a strong pumping


heart to circulate life-giving blood, and
this includes to the heart muscle itself

If the coronary arteries become blocked, the


cardiac muscle begins to fail, and so the blood
circulation decreases, which includes the
circulation to the heart muscle itself
Risk Factors
Uncontrollable Controllable

• Sex • High blood pressure


• Hereditary
• High blood
• Race
cholesterol
• Age
• Smoking
• Physical activity
• Obesity
• Diabetes
• Stress and anger
Screening and Diagnosis

me mea shows
as u su res
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icif
ec
od

sp

coronaries
bl o
electrical

Electro- Stress Coronary


cardiogram Test Angiography

Sit
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im Narrowin
Other Tests Include ...
• Blood tests: used to evaluate kidney and thyroid
function as well as to check cholesterol levels
and the presence of anemia.
• Chest X-ray: shows the size of your heart and
whether there is fluid build up around the heart
and lungs.
• Echocardiogram: shows a graphic outline of the
heart’s movement
• Ejection fraction (EF): determines how well your
heart pumps with each beat.
Treatment
 Many people are able to manage
coronary artery disease with lifestyle
changes and medications.

 Other people with severe coronary


artery disease may need angioplasty or
surgery.
Treatment (continued)

1) Stenting

• a stent is introduced into a blood vessel on a balloon


catheter and advanced into the blocked area of the artery
• the balloon is then inflated and causes the stent to expand
until it fits the inner wall of the vessel, conforming to
contours as needed
• the balloon is then deflated and drawn back
• The stent stays in place permanently, holding the vessel
open and improving the flow of blood.
Treatment (continued)

2) Angioplasty
• a balloon catheter is passed through the guiding catheter to the
area near the narrowing. A guide wire inside the balloon catheter
is then advanced through the artery until the tip is beyond the
narrowing.
• the angioplasty catheter is moved over the guide wire until the
balloon is within the narrowed segment.
• balloon is inflated, compressing the plaque against the artery
wall
• once plaque has been compressed and the artery has been
sufficiently opened, the balloon catheter will be deflated and
removed.
Treatment (continued)

3) Bypass surgery

• healthy blood vessel is removed from leg, arm or chest


• blood vessel is used to create new blood flow path in your heart
• the “bypass graft” enables blood to reach your heart by flowing
around (bypassing)
the blocked portion
of the diseased
artery. The increased
blood flow reduces
angina and the risk
of heart attack.
• Get regular medical checkups.
• Control your blood pressure.
Prevention

• Check your cholesterol.


• Don’t smoke.
• Exercise regularly.
• Maintain a healthy weight.
• Eat a heart-healthy diet.
• Manage stress.
 Fatty liver is excessive accumulation of fat
inside the liver cells.
Fatty liver is the most common alcohol-
induced liver disorder. The liver is
enlarged, causing upper abdominal
discomfort on the right side.
Fatty Liver (Steatosis)

 Alcohol abuse can lead to the


accumulation of fat within hepatocytes,
the predominant cell type in the liver.
 A similar condition can also be seen in
some obese people who are not alcohol
abusers.
 Fatty liver is reversible if the patient stops
drinking, however, fatty liver can lead to
steatohepatitis.
 Steatohepatitis is fatty liver accompanied
by inflammation and this condition can
lead to scarring of the liver and cirrhosis.
Fatty Liver Disease

Normal liver Fatty liver (Steatosis)

Cirrhosis Steatohepatitis
- inflammation
- fibrosis