LIPID

Klasifikasi dan
Karakteristik Lipid,
Fungsi dan Peranan Lipid,
Biosintesis Lipid
 LIPID
■ Lipids are water-insoluble cellular components of
diverse structure that can be extracted by
nonpolar solvents.

■ Almost all fatty acids, the hydrocarbon

components of many lipids, have an even number
of carbon atoms (usually 12 to 24); they are
either saturated or unsaturated, with double
bonds almost always in the cis configuration.
 *

* *

Modified from Champe & Harvey,

* polar, more amphipathic lipids Biochemistry, 2nd Edition, Fig. 16.1.

Major Categories

1. Neutral Lipids: nonpolar esters of fatty acids with alcohols,

glycerol, and cholesterol.
 Polar
Head *
Group
Nonpolar Tail

* *

General Polar Lipid

Structure
* polar, more amphipathic lipids
Modified from Champe & Harvey,
Biochemistry, 2nd Edition, Fig. 16.1.

2. Polar Lipids: contain a polar group such as phosphate,

sulfate, or a carbohydrate. Consequently considered
amphipathic.

Important components of membranes. phospholipids –

phosphate group
sulpholipid – sulphate group glycolipid – sugar moiety
 LIPID
■ 1. Neutral Lipids
■ Triacylglycerols contain three fatty acid
molecules esterified to the three hydroxyl
groups of glycerol. Simple triacylglycerols
contain only one type of fatty acid; mixed
triacylglycerols, two or three types.
Triacylglycerols are primarily storage fats; they
are present in many foods.
 LIPID
■ The fats and oils used almost universally as stored forms of
energy in living organisms are derivatives of fatty acids.

■ Fatty Acids Are Hydrocarbon Derivatives

Fatty acids are carboxylic acids with hydrocarbon chains
ranging from 4 to 36 carbons long (C4 to C36).

■ In some fatty acids, this chain is unbranched and fully

saturated (contains no double bonds); in others the chain
contains one or more double bonds
 Asam Lemak
* Merupakan Asam Monokarboksilat
O
* Rumus : R – C – OH
* R adalah gugus alkil
O
* R – C – adalah gugus asil (acyl)
ujung metil ujung karboksil
CH3 – (CH2)n – CH2 – CH2 – COOH
   1

3/9/2018 7
• ASAM LEMAK JENUH
• Tak ada ikatan rangkap
• Rumus umum CnH2n+1COOH
• As. Lemak jenuh rantai panjang
bersifat padat pd suhu kamar
• Contoh :
• asam butirat (C4),
• asam stearat (C18)
• asam palmitat (C16)
CH3(CH2)14COOH
3/9/2018 8
Nomenclature
• Common name most commonly used
• The systematic name for saturated acids ends in -anoic. Unsaturated fatty acids
ends in -enoic.
• The number one carbon is the carboxyl carbon
• Carbon #1 = alpha carbon
• Carbon #2 = beta carbon
• Carbon #3 = gamma carbon
• Omega vs. delta fatty acids
• Double bonds counted from the first carbon are delta desaturations
• Double bonds counting from the methyl end are the omega desaturations

Trivial IUPAC Carboxyl Omega

Oleic Acid 9-octadecenoic acid 18:1 9 18:1 9

Linoleic Acid 9, 12-octadecenoic acid 18:2 9,12 18:2 6

Essential FA- those that humans can not make but are required to
Sustain growth - Linolenic 3 and Arachadonic 6
 Asam Lemak Tak Jenuh
• C pada ujung metil adalah Cω
• Ikatan rangkap: ada yang 1 ada yang >1
• Asam lemak ω3  ikatan rangkap pertama dihitung
dari ujung metil terletak antara no 3 dan 4
CH3 – CH2 – CH = CH -------COOH
ujung metil ujung karboksil
• Lain2:
• Asam lemak ω-6
• Asam lemak ω-9

3/9/2018 10
• PUFA ( Poly unsaturated fatty acids)

• Ada > 1 ikatan rangkap, contoh :

- Asam linoleat (18:2ω-6) or (C18:2;9,12)
- Asam linolenat (18:3ω-3) or (C18:3;9,12,15)
- Asam arakhidonat (20:4ω-6) atau
(C20:4; 5,8,11,14)

3/9/2018 11
 LIPID
■ The longer the fatty acyl chain and the fewer the double
bonds, the lower is the solubility in water.
■ The carboxylic acid group is polar (and ionized at neutral pH)
and accounts for the slight solubility of short-chain fatty acids
in water.
■ Melting points are also strongly influenced by the length and
degree of unsaturation of the hydrocarbon chain. At room
temperature (25 C), the saturated fatty acids from 12:0 to
24:0 have a waxy consistency, whereas unsaturated fatty
acids of these lengths are oily liquids.
The packing of fatty acids into stable aggregates
 LIPID
■ Triacylglycerols Are Fatty Acid Esters of Glycerol

Glycerol and a triacylglycerol. The

mixed triacylglycerol
shown here has three different fatty
acids attached to the glycerol
backbone. When glycerol has two
different fatty acids at C-1 and
C-3, the C-2 is a chiral center
 Lipid functions

Some common types of storage and membrane lipids

Lipid functions
Lipids are used in

Fuel storage

Hormones

Signal transduction messenger

Membranes

Membrane lipids:

Phospholipid

Glycolipid

Cholesterol
 LIPID
■ Triacylglycerols Provide Stored Energy and Insulation

In vertebrates, specialized cells called adipocytes, or fat cells, store large amounts
of triacylglycerols as fat dropletsthat nearly fill the cell

Capillary
adipocytes,

Cross section of four guinea pig adipocytes, showing huge fat droplets that virtually
fill the cells. Also visible are several capillaries in cross section.
 LIPID
■ Triacylglycerols Provide Stored Energy and Insulation

Triacylglycerols are also stored as oils in the seeds of many types of plants, providing
energy and biosynthetic precursors during seed germination

(b) Cross section of a cotyledon cell from a seed of the plant

Arabidopsis. The large dark structures are protein bodies,
which are surrounded by stored oils in the light-colored oil
bodies

Adipocytes and germinating seeds contain lipases,

enzymes that catalyze the hydrolysis of stored
triacylglycerols, releasing fatty acids for export to sites
where they are required as fuel.
 LIPID
■ Triacylglycerols Provide Stored Energy and Insulation

There are two significant advantages to using triacylglycerols

as stored fuels, rather than polysaccharides such as glycogen and
starch.

First, because the carbon atoms of fatty acids are more reduced than
those of sugars, oxidation of triacylglycerols yields more than twice as
much energy, gram for gram, as the oxidation of carbohydrates.

Second, because triacylglycerols are hydrophobic and therefore

unhydrated, the organism that carries fat as fuel does not have to carry
the extra weight of water of hydration that is associated with stored
polysaccharides (2 g per gram of polysaccharide).
 LIPID
■ Triacylglycerols Provide Stored Energy and Insulation

In some animals, triacylglycerols stored under the skin serve not only as energy stores
but as insulation against low temperatures. Seals, walruses, penguins, and other
warm-blooded polar animals are amply padded with triacylglycerols

Sperm whale
 LIPID
> Many Foods Contain Triacylglycerols

Triacylglycerols containing only saturated fatty

acids, such as tristearin, the major component
of beef fat, are white, greasy solids at room
temperature

The unpleasant taste and smell associated

with rancidity result from the oxidative
cleavage of the double bonds in
unsaturated fatty acids, which produces
aldehydes and carboxylic acids of shorter
chain length and therefore higher volatility
 LIPID
> Many Foods Contain Triacylglycerols

Fatty acid content of palm oil

Type of fatty acid Saturated (48,8 %) pct
Myristic saturated C14 1.0%
Palmitic saturated C16 43.5%
Stearic saturated C18 4.3%
Oleic monounsaturated
Unsaturated (45,7 %) 36.6%
C18
Linoleic polyunsaturated
9.1%
C18
Other/Unknown 5.5%
 LIPID
>Waxes Serve as Energy Stores and Water Repellents
Biological waxes are esters of long-chain (C14 to C36)
saturated and unsaturated fatty acids with long-chain
(C16 to C30) alcohols. Their melting points (60 to 100
oC) are generally higher than those of

triacylglycerols.

• Waterfoul feathers (Bulu unggas air)

• Shiny leaves, Taro (keladi)

Manufacture of lotions, ointments, and

Polishes

• Lanolin
• Carnouba
• Spermaceti

Triacontanoylpalmitate, the major component of beeswax, is an ester

of palmitic acid with the alcohol triacontanol.
 LIPID
2. Polar Lipids
■ Structural Lipids in Membranes
 LIPID
2. Polar Lipids
■ Structural Lipids in Membranes
• Glycerophospholipids Are Derivatives of Phosphatidic Acid

Glycerophospholipids, also called phosphoglycerides, are membrane lipids in which

two fatty acids are attached in ester linkage to the first and second carbons of
glycerol, and a highly polar or charged group is attached through a phosphodiester
linkage to the third carbon.

L-Glycerol 3-phosphate, the backbone of phospholipids

 LIPID
• Glycerophospholipids Are Derivatives of Phosphatidic Acid
 LIPID
• Glycerophospholipids Are Derivatives of Phosphatidic Acid
 LIPID
• Some Phospholipids Have Ether-Linked Fatty Acids

Vertebrate heart tissue is uniquely enriched Platelet-activating factor, is a potent molecular

in ether lipids; about half of the heart signal which is released from leukocytes called
phospholipids are plasmalogens. basophils and stimulates platelet aggregation and
the release of serotonin (a vasoconstrictor) from
The membranes of halophilic bacteria, ciliated
platelets
protists, and certain invertebrates also contain
high proportions of ether lipids.
 LIPID
• Chloroplasts Contain Galactolipids and Sulfolipids

In monogalactosyldiacylglycerols (MGDGs) and digalactosyldiacylglycerols

(DGDGs), almost all the acyl groups are derived from linoleic acid (18:2(9,12)) and
the head groups are uncharged.
 LIPID
• Chloroplasts Contain Galactolipids and Sulfolipids

In the sulfolipid 6-sulfo- 6-deoxy--D glucopyranosyldiacylglycerol, the sulfonate

carries a fixed negative charge.
 LIPID
• Archaebacteria Contain Unique Membrane Lipids

Membrane lipids containing long-chain (32 carbons) branched hydrocarbons

linked at each end to glycerol. These linkages are through ether bonds, which are
much more stable to hydrolysis at low pH and high temperature than are the
ester bonds found in the lipids of eubacteria and eukaryotes
 LIPID
• Sphingolipids Are Derivatives of Sphingosine

Sphingolipids are composed of one molecule of the long-chain amino

alcohol sphingosine (also called 4-sphingenine) or one of its derivatives,
one molecule of a long-chain fatty acid, and a polar head group that is
joined by a glycosidic linkage in some cases and by a phosphodiester in
others
 LIPID
• Sphingolipids Are Derivatives of Sphingosine
 LIPID
• Sphingolipids Are Derivatives of Sphingosine

Gangliosides, the most complex sphingolipids, have oligosaccharides as

their polar head groups and one or more residues of N-acetylneuraminic
acid (Neu5Ac), a sialic acid (often simply called “sialic acid”), at the
termini.

Sialic acid gives gangliosides the negative

charge at pH 7 that distinguishes them from
globosides.

Gangliosides with one sialic acid residue are in

the GM (M for mono-) series,

those with two are in the GD (D

for di-) series,

(GT, three sialic acid residues; GQ, four).

 LIPID
• Sphingolipids Are Derivatives of Sphingosine

Sphingomyelins
 LIPID
• Sphingolipids at Cell Surfaces Are Sites of Biological Recognition
• Many of these are especially prominent in the plasma membranes of neurons, and some
are clearly recognition sites on the cell surface, but a specific function for only a few
sphingolipids has been discovered thus far.

The carbohydrate moieties of certain sphingolipids define the human blood groups and
therefore determine the type of blood that individuals can safely receive in blood
transfusions

• MHN

• Multi Histocompatibility Complexe (MHC) proteins - cell recognition in immunity

 LIPID
• Phospholipids and Sphingolipids Are Degraded in Lysosomes
 LIPID
• Representations of Membrane Lipids
 LIPID
• Sterols Have Four Fused Carbon Rings

The characteristic structure of this fifth group of

membrane lipids is the steroid nucleus, consisting of
four fused rings, three with six carbons and one with
five.

Cholesterol, the major sterol in animal tissues, is

amphipathic, with a polar head group (the hydroxyl
group at C-3) and a nonpolar hydrocarbon body (the
steroid nucleus and the hydrocarbon side chain at C-
17), about as long as a 16- carbon fatty acid in its
extended form
 LIPID
• Sterols Have Four Fused Carbon Rings

Similar sterols are found in other eukaryotes: stigmasterol in plants and

ergosterol in fungi, for example.

Bacteria cannot synthesize sterols; a few bacterial species, however, can

incorporate exogenous sterols into their membranes.

The sterols of all eukaryotes are synthesized from simple five carbon
isoprene subunits, as are the fat-soluble vitamins, quinones, and dolichols

In addition to their roles as membrane constituents, the sterols serve as

precursors for a variety of products with specific biological activities. Steroid
hormones, for example, are potent biological signals that regulate gene
expression.

Bile acids are polar derivatives of cholesterol that act as detergents in the
intestine, emulsifying dietary fats to make them more readily accessible to
digestive lipases
 LIPID
■ Lipids as Signals, Cofactors, and Pigments

Active roles in the metabolic traffic as metabolites and messengers.

Some serve as potent signals—as hormones, carried in the blood from
one tissue to another, or as intracellular messengers generated in
response to an extracellular signal (hormone or growth factor).
 LIPID
■ Lipids as Signals, Cofactors, and Pigments
• Phosphatidylinositols and Sphingosine Derivatives Act as Intracellular
Signals

Phosphatidylinositol and its phosphorylated derivatives act at several

levels to regulate cell structure and metabolism.

Phosphatidylinositol 4,5-bisphosphate in the cytoplasmic (inner) face of

plasma membranes serves as a specific binding site for certain cytoskeletal
proteins and for some soluble proteins involved in membrane fusion during
exocytosis.

It also serves as a reservoir of messenger molecules that are released inside

the cell in response to extracellular signals interacting with specific receptors
on the outer surface of the plasma membrane.
 LIPID
■ Lipids as Signals, Cofactors, and Pigments

• Phosphatidylinositols and Sphingosine Derivatives Act as Intracellular

Signals
 LIPID
■ Lipids as Signals, Cofactors, and Pigments

• Phosphatidylinositols and Sphingosine Derivatives Act as Intracellular

Signals

Membrane sphingolipids also can serve as sources of intracellular

messengers.

Both ceramide and sphingomyelin are potent regulators of protein

kinases, and ceramide or its derivatives are known to be involved in the
regulation of cell division, differentiation, migration, and programmed
cell death.
 LIPID
■ Lipids as Signals, Cofactors, and Pigments

• Eicosanoids Carry Messages to Nearby Cells

All eicosanoids are derived from arachidonic acid (20:4 (5,8,11,14))
 LIPID
■ Lipids as Signals, Cofactors, and Pigments

• Eicosanoids Carry Messages to Nearby Cells

All eicosanoids are derived from arachidonic acid (20:4 (5,8,11,14))

Prostaglandins act in many tissues by regulating the synthesis of the

intracellular messenger 3,5-cyclic AMP (cAMP). Because cAMP mediates
the action of diverse hormones, the prostaglandins affect a wide range of
cellular and tissue functions.

Thromboxanes have a six-membered ring containing an ether. They are

produced by platelets (also called thrombocytes) and act in the
formation of blood clots and the reduction of blood flow to the site of a
clot
 LIPID
■ Lipids as Signals, Cofactors, and Pigments

• Eicosanoids Carry Messages to Nearby Cells

All eicosanoids are derived from arachidonic acid (20:4 (5,8,11,14))

Leukotrienes, contain three conjugated double bonds. They are powerful

biological signals. For example, leukotriene D4, derived from leukotriene
A4, induces contraction of the muscle lining the airways to the lung.

Overproduction of leukotrienes causes asthmatic attacks, and

leukotriene synthesis is one target of antiasthmatic drugs such as
prednisone
 LIPID
■ Lipids as Signals, Cofactors, and Pigments

• Steroid Hormones Carry Messages between Tissues

Steroids are oxidized derivatives of sterols; they have the sterol nucleus
but lack the alkyl chain attached to ring D of cholesterol, and they are
more polar than cholestrol.

The major groups of steroid hormones are the male and female sex
hormones and the hormones producedb y the adrenal cortex, cortisol
and aldosterone
 LIPID
■ Lipids as Signals, Cofactors, and Pigments

• Steroid Hormones Carry Messages between Tissues

Testosterone, the male sex hormone, is

produced in the testes.
Estradiol, one of the female sex
hormones, is produced in the ovaries
and placenta.
Cortisol and aldosterone are hormones
synthesized in the cortex of the adrenal
gland; they regulate glucose
metabolism and salt excretion,
respectively.
Prednisolone and prednisone are
synthetic steroids used as
antiinflammatory agents.
 LIPID
■ Lipids as Signals, Cofactors, and Pigments

• Plants Use Phosphatidylinositols, Steroids, and Eicosanoid -like

Compounds in Signaling
Vascular plants contain phosphatidylinositol 4,5-bisphosphate, as well as the
phospholipase that releases IP3, and they use IP3 to regulate the intracellular
concentration of Ca2.
 LIPID
■ Lipids as Signals, Cofactors, and Pigments

• Vitamins A and D Are Hormone Precursors

 LIPID
■ Lipids as Signals, Cofactors, and Pigments

• Vitamins A and D Are Hormone Precursors

 LIPID
■ LIPID BIOSYNTHESIS
• Biosynthesis of Fatty Acids and Eicosanoids

Fatty acid biosynthesis and breakdown occur by different pathways, are

catalyzed by different sets of enzymes, and take place in different parts
of the cell.

Moreover, biosynthesis requires the participation of a three-carbon

intermediate, malonyl-CoA, that is not involved in fatty acid breakdown.
 LIPID
■ LIPID BIOSYNTHESIS
• Biosynthesis of Fatty Acids and Eicosanoids
Malonyl-CoA Is Formed from Acetyl-CoA and Bicarbonate

Acetyl CoA carboxylase

 LIPID
■ LIPID BIOSYNTHESIS
• Biosynthesis of Fatty Acids and Eicosanoids
Fatty Acid Synthesis Proceeds in a Repeating Reaction Sequence

A saturated acyl group produced by this set of reactions becomes the

substrate for subsequent condensation with an activated malonyl group.
With each passage through the cycle, the fatty acyl chain is extended by
two carbons. When the chain length reaches 16 carbons, the product
leaves the cycle.

All the reactions in the synthetic process are catalyzed by a multienzyme

complex, fatty acid synthase.
 Addition of two carbons to a growing fatty
acyl chain: a four-step sequence.

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 -keto product of this
condensation is then reduced in three more steps
nearly identical to the reactions of oxidation, but
in the reverse sequence:
2 The -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.
 LIPID
■ LIPID BIOSYNTHESIS
• Biosynthesis of Fatty Acids and Eicosanoids
The Fatty Acid Synthase Complex Has Seven Different Active Sites

The fatty acid synthase complex is a polypeptide containing Seven

enzyme activities

In bacteria and plants, the individual enzymes of the fatty acid synthase
system are separate, and the acyl radicals are found in combination with
a protein called the acyl carrier protein (ACP).

In mammals, the fatty acid synthase complex is a dimer comprising two

identical monomers, each containing all seven enzyme activities of fatty
acid synthaseon one polypeptide chain
 LIPID
■ LIPID BIOSYNTHESIS
• Biosynthesis of Fatty Acids and Eicosanoids

The Fatty Acid Synthase Complex Has Seven Different Active Sites
 Tahapan Sintesis Asam Lemak
1. Reaksi awal
- Karboksilasi gugus asetil menjadi malonil-KoA
- Reaksi dikatalis oleh asetil KoA karboksilase

 Biotin-enzim + ATP + HCO3- enzim CO2-biotin-ADP + Pi

+

 CO2-biotin-enzim + asetil KoA malonil KoA +biotin-enzim

 2. Pemanjangan rantai putaran 1:

 pembentukan asetil ACP dan malonil ACP

 reaksi dikatalisoleh asetil transasilasedan malonil
transasilase
Asetil KoA + ACP asetil ACP + KoA
Malonil KoA + ACP malonil ACP + KoA
 Reaksi kondensasi
 Asetil ACP + malonil ACP  asetoasetil ACP + ACP +
CO2
 Reaksi Kondensasi
Reduksi gugus keto pada C-3 menjadi gugus
metilen

 (1) asetoasetil ACP direduksi menjadi 3-hidroksi

butiril ACP. Reaksi ini memerlukan NADPH sebagai
pereduksi.
 (2) Dehidrasi 3-hidroksi butiril ACP menjadi krrotonil
ACP (merupakan trans-2 enoyl ACP).
 (3) Reduksi krotonil ACP menjadi butiril ACP dengan
menggunakan senyawa peredusi NADPH, yang
dikatalis oleh enzim enoyl ACP reduktase.
Reaksi reduksi I
Reaksi dehidrasi
Reaksi reduksi II
3. Pemanjangan rantai 2
Reaksi pemanjangan rantai putaran 2 : kondensasi
butiril ACP dengan malonil ACP membentuk C6--
ketoasil ACP
Reaksi ini sama dengan reaksi pemanjangan rantai
putaran 1. Selanjutnya pemanjangan rantai diteruskan
sampai terbentuk C16 asil ACP
 Stoikiometri Sintesis Asam palmitat

 Asetil KoA + 7 Malonil KoA + 14 NADPH + 20 H+

→ palmitat + 7 CO2 + 14 NADP+ + 8 KoA + 6 H2O
 Reaksi tersebut memerlukan malonil KoA yang disintesis
dari :
7 Asetil KoA + 7 CO2 + 7 ATP → 7 malonil KoA + 7
ADP + 7 Pi + 14 H+
 Jadi stoikhiometri keseluruhan sintesis palmitat adalah:
8 Asetil KoA + 7 ATP + 14 NADPH + 6 H+
→ palmitat + 14 NADP+ + 8 KoA + 6 H2O + 7 ADP + 7 Pi
PEMBENTUKAN IKATAN RANGKAP
a. Asam lemak tak jenuh tunggal
Pembentukan asam lemak tak jenuh tunggal dikatalisis oleh sistem
enzim : Δ9 Desaturase
Prosesnya terjadi di dalam retikulum endoplasma
b. Asam lemak tak jenuh ganda

Pada binatang dan manusia, penambahan ikatan

rangkap berlangsung di sepanjang rantai yang terletak di : antara ikatan
rangkap yang sudah ada dengan gugus karboksil dari molekul asam lemak
yang bersangkutan
Dalam sebagian besar tubuh hewan ( dan manusia ),
ikatan rangkap dapat disisipkan pada posisi :
3 , 4 , 5 , 6 , 9
( yang dihitung dari ujung terminal karboksil )
dan tidak pernah di atas posisi 9.
Pada tanaman, penambahan ikatan rangkap berlangsung di sepanjang
rantai yang terletak di : antara ikatan rangkap yang sudah ada dengan
atom karbon –  dari molekul asam lemak yang bersangkutan

Tanaman mampu menyisipkan ikatan rangkap pada posisi di atas 9

Misalnya pada posisi 12 , 15
Dari keterangan di atas menjadi jelas mengapa ASAM LINOLEAT dan
ASAM  – LINOLEAT tidak bisa disintesis sendiri di dalam tubuh
manusia dan hewan
Namun karena keduanya tetap diperlukan di dalam tubuh untuk
menjadi ‘prekursor’ pada sintesis produk yang lain, maka kedua
asam lemak tersebut perlu ada di dalam diet / makanan
Oleh karena itu, keduanya disebut sebagai asam lemak esensial.
PROSES PEMAKAIAN ASAM LEMAK SBG
BAHAN BAKAR

 3 tahap :
1. Mobilisasi triasilgliserol
2. Aktivasi dan transportasi asam
lemak
3. Pemecahan asam lemak menjadi
asetil koA (β-oksidasi)
 Mobilisasi
asam lemak
• Hidrolisis triasilgliserol
menjadi asam lemak dan
gliserol di dalam sel
lemak
• pelepasan asam lemak dari
sel lemak, ditransport ke
jaringan-jaringan yang
memerlukan energi
Cells take up LDL by receptor-mediated endocytosis
Endoplasm
ic
reticulum
Nucleus

Clathrin- d
coated vesicle
Clathrin-
2 coated
pit

Recycling of
LDL
receptors
Hidrolisis triasilgliserol
 Metabolisme gliserol
• Gliserol yang terbentuk pada lipolisis diabsorpsi oleh liver
•difosforilasi dan dioksidasi menjadi dihidroksiaseton fosfat
•diisomerisasi menjadi gliseraldehid-3-fosfat
• Jadi gliserol dapat diubah menjadi piruvat atau glukosa di hati.
 Metabolisme asam lemak

 β-oksidasi asam lemak

 Tahapan :
1. Aktivasi asam lemak
2. Transport asil lemak koA (Fatty Acyl CoA)
3. Reaksi-reaksi :
 Oksidasi
 Hidrasi

 Oksidasi

 Pemutusan ikatan C-C (reaksi thiolisis)

 Aktivasi Asam Lemak

 Asam lemakdioksidasi di mitokondria

 Asam lemak mengalamiaktivasi sebelum memasuki
mitokondria
 ATP memacu pembentukan ikatan tioesterantara gugus
karboksil asam lemak dan gugus sulf hidril pada KoA
 Reaksi aktivasi berlangsung di membran luar
mitokondria dikatalisoleh enzim asil KoA sintetase
Reaksi:

FA + CoA + ATP asil lemak koA + AMP + 2Pi + 34 kJ/mol

 Trasportasi asil-koA
• Gugus asil pada asil-koA ditransfer ke gugus OH
karnitin membentuk asil karnitin yg dikatalis
karnitin asiltransferase I pd membran luar
mitokondria
• Asil karnitin melintasi membran dalam mitokondria
yg dikatalis enzim translokase
• Gugus asil ditransfer kembali ke koA yg berada dalam
matriks mit. yg dikatalis karnitin asiltransferase II
• enzim translokase memindah kembali karnitin ke sitosol
 Trasportasi esterAsil-koA
Rate-limiting step of FA oxidation
 Step2 : Hidrasi
• Mengkatalisis hidrasi
trans enoyl CoA
• Penambahan gugus
hidroksi pada C no. 3
• Ensim bersifat
stereospesifik
• Menghasilkan 3-
L- hidroksiasil Co.
A
 Step 3 : dehidrogenasi/ oksidasi
• Mengkatalisis oksidasi -OH
pada C no. 3 / C β 
menjadi keton
• Akseptor elektronnya :
NAD+
 Step 4 : thiolisis
• β-Ketothiolase  mengkatalisis
pemecahan ikatan thioester.
• Asetil-koA  dilepas dan tersisa asil
lemak ko A yang terhubung dgn thio
sistein mll ikatan tioester.
• Tiol HSCoA menggantikan cistein
thiol, menghasilkan asil lemak-koA
(dengan pemendekan 2 C)
β-oksidasi asam palmitat
(a) Repeat S equence
C14 Acetyl -CoA

c12 Acetyl -CoA

c10 Acetyl -CoA
Cs Acetyl -CoA
c6 Acetyl -CoA
c4 Acetyl -CoA

Acetyl -CoA

(b )
o x idation degrades an acyi-CoA to prod uce acetyi-CoA molecules for TCA cycle

0 0

SQ>.\ A KAA
' 0

·
0

A so..
0
so..) 0

IICoA Asc... Each progressive step

)
ll
0
0
releases acetyi-CoA and
I()
so.. .•..Jl..,.,... reduces carbon chain
0 0
length by 2 carbons
S C < > ' A sc..,.
• 0 )
0

, sc) )l..so..
0

'
S C M
A so..
0

Aso..
Perolehan ATP pada oksidasi
asam lemak
 Energi yang diperoleh pada oksidasi asam lemak dapat
dihitung berdasarkan stoikhiometri setiap siklus sebagai
berikut:
 asilKoA dipendekkan sebanyak 2 karbon dengan
pelepasan FADH2, NADH dan asetil KoA
 Reaksi :
Cn-asil KoA + FAD + NAD+ + H2O + KoA 
Cn-2-asil KoA + FADH2 + NADH + asetil KoA + H+
 Perolehan ATP pada Oksidasi Asam Palmitat :

 Pemecahan palmitoil KoA (C18-asil KoA) : perlu 7 daur reaksi

 Pada daur ke -7, C4-ketoasil KoA mengalami tiolisis menjadi dua molekul
asetil KoA
Palmitoil KoA + 7 FAD + 7 NAD+ + 7 KoA + 7 H2O →
8 asetil KoA + 7 FADH 2 +7 NADH + 7 H +
 Pembentukan ATP :
 Oksidasi NADH → 2,5 ATP
 FADH2→ 1,5 ATP
 asetil KoA → 10 ATP
 Jumlah ATP yang terbentuk pada oksidasi palmitoil KoA : 108
 10,5 dari 7 FADH2
 17,5 dari 7 NADH
 80 dari 8 mol asetil KoA
 Dua ikatan fosfat energi tinggi dipakai untuk mengaktifkan palmitat (ATP
→ AMP + 2 Pi)
Jadi oksidasi sempurnasatu mol palmitat menghasilkan 106 AT P
Degradasi asam
lemak tak jenuh
 Membutuhkan 2
enzim tambahan yi
 Enoyl CoA isomerase
 2,4 dienoyl CoA
reduktase
Degradasi asam lemak dengan jumlah
atom C ganjil
 Degradasi FA dgn jumlah C ganjil  pd akhir
beta oksidasi  asetoasetil Ko A  dipecah
akan menghasilkan propionil Ko A dan Asetil
Ko A
 Propionil Ko A  diubah menjadi
metilmalonil Ko A  suksinil KoA  TCA
Propionyl Col

Succinyl Col
 Penggunaan Asetil KoA

 Asetil KoA yang terbentuk pada oksidasi asam lemak

dapat masuk ke dalam siklus asam sitrat hanya apabila
degradasi lemak dan degradasi karbohidrat berjalan
seimbang.
 Proses masuknyaasetil KoA ke dalam siklus asam
sitrat tergantung pada keberadaan oksaloasetat dari
sitrat. Konsentrasi oksaloasetat rendah apabila
karbohidrat tidak tersedia atau digunakan secara
berlebihan.
 Secara normal aksaloasetat dihasilkan dari piruvat
(produk glikolisis) oleh enzim piruvat karboksilase.
 Stllt(e 2

l.sAcetyl-Co 1

Citric
acid cyc1c

S t age3 NADH.FADH2

R(!:spiral,ory
(electron transfer)
L _ _ chaiu

+ P;
 Pembentukan badan keton
 Selama puasa atau pada diabetes
 oksaloasetat dikonsumsi untuk menghasilkan glukosa melalui
jalur glukoneogenesis, sehingga tidak ada yang dapat
digunakan untuk kondensasidengan asetil KoA.
 asetil KoA diubah menjadi asetoasetatdan D-3- hidroksibutirat.
Senyawa-senyawaasetoasetat, D-3- hidroksibutiratdan aseton
dinamakan badan-badan keton.
 Penderita diabetesyang tidak diobati, maka badan-badan keton
ditemukandalamdarahnyadengan kadaryang tinggi.
 Badan-badan keton
 Tempat pembentukan asetoasetat dan D-3-
hidroksibutirat : liver
 Senyawa ini berdifusi dari mitokondria liver menuju
darah kemudian ditransport ke jaringan-jaringan
perifer.
 Otot jantung dan korteks ginjal menggunakan
asetoasetatsebagai pengganti glukosa
 Otak juga dapat beradaptasi ketika dalam kondisi
berpuasa atau diabetes sehinggadapat menggunakan
asetoasetat
 Selama puasa jangka lama, 75 % bahan bakar yang diperlukan
otak dipenuhi oleh badan-badan keton.
 FATCill
FASTING or DIABETES BWO D r - - - - - - - -
-
J...t-- Glycerol • a
! A '- Fatty acids........
liVIRCill Glycerol
Fatty acid s
Glycerol _ . . Glucose- + -

HEART-MUSClE CELL
RENAL-CORTEXCELL
IRAIN CEll DURIN6 STARVATION

, _ -; . ( Ketone bod ies

l
AcetyiCoA
t
Reaksi pembentukan badan keton
 /CoA
s\
c 0 /CoA
ICH CoA s\
3
L "" I
c 0

/CoA (i) H2C

\c
s\ I
0

c 0 c
ICH 3 Acetoacetyl CoA
 /oA
CoA
s\
C= O

===:/=·
0 H2< ,,...CH3
C'
H2CI "'oH
\
C= o
-
0
Acetoacetyl CoA 3·Hydroxy·3·methyl·
glutaryl CoA
 /CoA
s\
C=O
I
H2\ ,.....CH3
( ......

H2C
I "oH
\ C= o
0
/'' -
3-Hydroxy-3-methyl· Acetoacetate
glutaryl CoA
 H3C\ .......OH
c'
I " H
H2C
\ C= O
0
f' -
o·3·Hydroxy·
butyrate
H3C\
/ =0
H3C
Acetoacetate Acetone
 Reaksi degradasi badan keton
 3-hidroksibutirat dioksidasi menghasilkan
asetoasetat dan NADH (selanjutnya diproses di
rantai fosforilasi oksidatif menghasilkan energi)
 Asetoasetat diaktivasi melalui transfer KoA dari
suksinil KoA membentuk asetoasetil KoA oleh
enzim KoA transferase. Kemudian asetoasetil
KoA didegradasi oleh tiolase menghasilkan asetil
KoA (siap diproses di siklus asam sitrat untuk
menghasilkan energi)
 H

,,,.----0
-
, .----0
,,
o' - 0,
D·3·Hydroxybutyrate Acetoacetate
 Acetoacetate
- - Succinyl CoA
CoA
transferase

Acetoacetyl CoA

CoA
Thiolase

2 Acetyl CoA