Metabolisme Lemak

What is a Lipid
• Lipids: a heterogeneous class of naturally occurring organic
compounds classified together on the basis of common
solubility properties
– insoluble in water, but soluble in aprotic organic solvents
including diethyl ether, chloroform, methylene chloride,
and acetone
– Amphipathic in nature
• Lipids include:
– Open Chain forms
– fatty acids, triacylglycerols, sphingolipids,
phosphoacylglycerols, glycolipids,
– lipid-soluble vitamins
– prostaglandins, leukotrienes, and thromboxanes
• Cyclic forms
– cholesterol, steroid hormones, and bile acids
 FUNGSI LEMAK BAGI TUBUH
1. Komponen struktur membran
2. Lapisan pelindung pada beberapa jasad
Fungsi membran yang sebagian besar
mengandung lemak, diantaranya adalah berrier
permeabel untuk mencegah infeksi dan kehilangan
(penambahan) air berlebihan
3. Bentuk energi cadangan
4. Kofakator atau prekursor enzim  untuk aktivitas
enzim seperti fosfolipid dalam darah, koenzim A,
5. Hormon dan vitamin, prostaglandin (PG)
Contoh: asam arakidonat adalah prekursor untuk
biosintesis PG.
6. Insulasi barrier  untuk menghindari panas,
tekanan listrik dan fisik
Lemak di dalam tubuh terus menerus dirombak dan
disintesa melalui berbagai proses metabolisme.
 Lipids
• Trigliserida – most plentiful in body and diet
– Glyserol + 3 asam lemak
– Saturated, monounsaturated, polyunsaturated
– Mengandung energi 2 kali lebih banyak dibanding karbohidrat
dan protein
• Phospholipids – Lipid complex mengandung phosphate
– Glycerol + 2 asam lemak dan 1 phosphate group
• Cholesterol – Turunan Gliserida
– 80% of all cholesterol is formed in the liver to make bile salts
 Lipid
• Oxidized to produce ATP
• Excess stored in adipose tissue or liver
• Synthesize structural or important
molecules
– phospholipids of plasma membranes
– lipoproteins that transport cholesterol
– thromboplastin for blood clotting
– myelin sheaths to speed up nerve conduction
– cholesterol used to synthesize bile salts and
steroid hormones.
 Penyimpanan Trigliserida
• Adipose tissue
– 50% subcutaneous, 12% near kidneys, 15% in omenta, 15%
in genital area, 8% between muscles
• Fats in adipose tissue are ever-changing
– released, transported & deposited in other adipose
• Triglycerides store more easily than glycogen
– do not exert osmotic pressure on cell membranes
– are hydrophobic
 Oxidation and Reduction
• Biological oxidation involves the loss of (electrons) hydrogen atoms
– Dehydration reactions require coenzymes to transfer hydrogen atoms
to another compound
– Common coenzymes of living cells that carry H+
• NAD (nicotinamide adenine dinucleotide)
• NADP (nicotinamide adenine dinucleotide phosphate)
• FAD (flavin adenine dinucleotide)
• Biological reduction is the addition of electrons (hydrogen atoms) to
a molecule
– Increases the potential energy of the molecule
 Fatty Acids
• Fatty acid: an unbranched-chain carboxylic acid, most commonly of 12 -
20 carbons, derived from hydrolysis of animal fats, vegetable oils, or
phosphodiacylglycerols of biological membranes
• In the shorthand notation for fatty acids
– the number of carbons and the number of double bonds in the
chain are shown by two numbers, separated by a colon
 FOOD LIPIDS
Food lipids : Triglycerides, Phospholipids, Cholesterol
Fatty Acids:
Number of C atom: SCFA (C1 - C6); MCFA (C6 – C12)
LCFA (> C12)
Process : Essential dan non-essential
Degree of saturated: saturated & unsaturated
Physical Properties of acyl lipids are obviously affected by
their individual Fatty Acids – a most obvious one being the
MELTING POINT
Example : membranes are incapable of operating with lipids
whose acyl chains are crystalline. For mammals, this means,
acyl chains must be fluid at about 37oC; and for poikilotherms
(organisms unable to regulate their own temperature) at
temp between about -10 oC and over 100 oC.
 Fatty Acids (Cont’d)
Length of fatty acid plays a role in its chemical character
• Usually contain even numbers of carbons (can contain
odd, depending on how they are biosynthesized)
• FA that contain C=C, are unsaturated: If contain only C-C
bonds, they are saturated
•
Fatty Acids (Cont’d)
In most unsaturated fatty acids, the cis isomer predominates; the
trans isomer is rare

• Unsaturated fatty acids have lower melting points than their

saturated counterparts; the greater the degree of unsaturation, the
lower the melting point
 Triacylglycerols
• Triacylglycerol (triglyceride): an ester of glycerol with three
fatty acids
– natural soaps are prepared by boiling triglycerides
(animal fats or vegetable oils) with NaOH, in a
reaction called saponification (Latin, sapo, soap)
 Soaps
• Soaps form water-
insoluble salts when used
in water containing Ca(II),
Mg(II), and Fe(III) ions
(hard water)

• Reactions with
acids/bases as catalysts

• Salts formed by
saponification
 Phosphoacylglycerols (Phospholipids)
• When one alcohol group of glycerol is esterified by a
phosphoric acid rather than by a carboxylic acid, phosphatidic
acid produced

• Phosphoacylglycerols (phosphoglycerides) are the second

most abundant group of naturally occurring lipids, and they
are found in plant and animal membranes
 Waxes
• A complex mixture of esters of long-chain
carboxylic acids and alcohols
• Found as protective coatings for plants and
animals
 Sphingolipids
• Contain sphingosine, a long-chain
amino alcohol sphingosine

• Found in plants and animals

• Abundant in nervous system

• Bares structural similarity to

phospholipids
•
Glycolipids
Glycolipid: a compound in
which a carbohydrate is bound
to an -OH of the lipid

• In most cases, sugar is either

glucose or galactose
– many glycolipids are
derived from
ceramides
• Glycolipids with complex
carbohydrate moiety that
contains more than 3 sugars
are known as gangliosides
(Fig. 8.8, p. 207)
 Steroids
• Steroids: a group
of lipids that have
fused-ring
structure of 3 six-
membered rings,
and 1 five-
membered ring.
 Sex Hormones
• Androgens: male sex hormones
– synthesized in the testes
– responsible for the development of male
secondary sex characteristics
– Testosterone
• Estrogens: female sex hormones
– synthesized in the ovaries
– responsible for the development of female
secondary sex characteristics and control of the
menstrual cycle
 Cholesterol
• The steroid of most interest in our discussion of
biological membranes is cholesterol
ASAM LEMAK
 adalah asam organik rantai panjang yang
mempunyai atom karbon 4 s/d 24 atau bahkan 36,
dan memiliki gugus karboksilat tunggal (-COOH)
serta ekor hidrokarbon non polar yang panjang (-
CH3).
misal : CH3(CH2)10-COOH (asam laurat)

KELOMPOK ASAM LEMAK

1. Asam lemak jenuh (ikatan tunggal)
(-CH2-CH2-CH2-CH2-)
2. Asam lemak tidak jenuh ( mempunyai ikatan
rangkap )
(-CH=CH-CH2-CH=CH-)
 TATA NAMA ASAM LEMAK TIDAK JENUH
A. Menganti kata ‘anoic’ (anoat) pada asam lemak jenuh
menjadi ‘enoic’ (enoat) dan ditambah di, tri, dst berdasarkan
jumlah ikatan rangkapnya.
Misal :
16:0  Hexadecanoic acid (asam heksadekanoat)
16:1  Hexadecenoic acid (asam heksadekenoat)
18:3  Octadecatrienoic acid
B. Dengan menggunakan ω (atau n) diikuti nomor atom C
ikatan rangkap pertama dan ∆ ditambah nomor-nomor atom
C dimana terdapat ikatan rangkapnya
- ω bila penomoran atom C pada asam lemak dimulai dari
ujung metil. Misal : 18:3n-3
- ∆ bila penomoran atom C dimulai dari gugus karboksil.
Misal : 18:3  18:3∆9,12,15
Systematic, Common & Shorthand Names of UFA

HOOC
18
17
16

15

14
1 2 6
13
18
3 4 12

16
5 6 9 11 8
14
7 8 10
12
10
Outside of Molecule Numbering
Inside of Molecule w Numbering
 Nomenclature Asam Lemak
• Standard nomenclature:

20:4 n6 n-Designation

Carbon chain length

NumberPosition of bonds
of double double bonds

20:4 D5,8,11,14 D-Designation

 Nomenclature Asam Lemak

Oleic acid – 18-carbon, monounsaturated, D9; n-9

Linoleic acid – 18-carbon, polyunsaturated, D9,12; n-6

Copyright 2005 Wadsworth Group, a division of Thomson Learning
 Chemical Names and Descriptions of some Common Fatty Acids
Common Name Carbon Double Scientific Name Sources
Atoms Bonds
Butyric acid 4 0 butanoic acid butterfat
Caproic Acid 6 0 hexanoic acid butterfat
Caprylic Acid 8 0 octanoic acid coconut oil
Capric Acid 10 0 decanoic acid coconut oil
Lauric Acid 12 0 dodecanoic acid coconut oil
Myristic Acid 14 0 tetradecanoic acid palm kernel oil
Palmitic Acid 16 0 hexadecanoic acid palm oil
Palmitoleic Acid 16 1 9-hexadecenoic acid animal fats
Stearic Acid 18 0 octadecanoic acid animal fats
Oleic Acid 18 1 9-octadecenoic acid olive oil
Vaccenic Acid 18 1 11-octadecenoic acid butterfat
Linoleic Acid 18 2 9,12-octadecadienoic acid grape seed oil
Alpha-Linolenic Acid (ALA) 18 3 9,12,15-octadecatrienoic acid flaxseed (linseed) oil

Gamma-Linolenic Acid (GLA) 18 3 6,9,12-octadecatrienoic acid borage oil

Arachidic Acid 20 0 eicosanoic acid peanut oil, fish oil
Gadoleic Acid 20 1 9-eicosenoic acid fish oil
Arachidonic Acid (AA) 20 4 5,8,11,14-eicosatetraenoic acid liver fats
EPA 20 5 5,8,11,14,17-eicosapentaenoic acid fish oil
Behenic acid 22 0 docosanoic acid rapeseed oil
Erucic acid 22 1 13-docosenoic acid rapeseed oil
DHA 22 6 4,7,10,13,16,19-docosahexaenoic acid fish oil
Lignoceric acid 24 0 tetracosanoic acid small amounts in most fats
TRIGLICERIDE / ACYLGLYCEROL /lemak netral
- Fat / lemak  pd suhu ruang berbentuk padat
- Oil / minyak  pd suhu ruang berbentuk cair
- Merupakan ikatan ester antara gliserol dengan asam lemak (-
OH dg –COOH)
- Acylglycerol terdapat mono, di, tri ester glycerol dg asam lemak
(R).
- Contoh : tristearoilglycerol / glycerol tristearat / tristearin
• TRIGLISERIDA
 Jenisnya tergantung pada identitas & letak ke-3 asam lemaknya
1. mengandung 1 jenis asam lemak  trigliserida sederhana
mis : tristearin, tripalmitin, triolein, dll
2. mengandung 2 tau lebih asam lemak yang berbeda 
trigliserida campuran.
Mis: minyak olive, mentega, & lemak makan yg lain.
 bersifat non polar, terhidrolisis jika dididihkan dengan asam
atau basa atau oleh enzim lipase dan menghasilkan asam
lemak atau garam dan gliserol
 Trigliserida & Asam lemak trans
• Asam lemak trans
- Alami (Asam vaccenic dan asam
linoleat terkonjugasi) :
jumlahnya terbatas di alam.
- Sintetis
– Hasil proses hidrogenasi parsial PUFA
dengan panas dan katalis
– Bahaya bagi kesehatan krn mengakibatkan
sakit jantung lebih kuat daripada asam
lemak jenuh (meningkatkan LDL dan
menurunkan HDL)
– Asam lemak linoleat terkonjugasi (C9, tr11
vs tr10, C12)

Copyright 2005 Wadsworth Group, a division of Thomson Learning

Release of Fatty Acids from Triacylglycerols

O
CH 2OC-R1 CH 2OH
O Lipases
CHOC-R 2 CHOH

O
CH 2OC-R3 CH 2OH
Triacylglycerol Glycerol
+
O O O
HOC-R 1 HOC-R 2 HOC-R 3
 Lipid Metabolism
• Digestion - Hydrolysis Reaction
Lipid Metabolism

• Started by breaking down of lipid in adipose cell, and

transporting fatty acid into blood stream by serum albumin
• Catabolism of fats involves two separate pathways
– Glycerol pathway
– Fatty acids pathway

36
Mobilization of triacylglycerols stored in adipose tissue.
Lipid Metabolism

• Glycerol is converted to glyceraldehyde phosphate

– Glyceraldehyde is ultimately converted into acetyl CoA
– Acetyl CoA enters the Krebs cycle
• Fatty acids undergo beta oxidation which produces:
– Two-carbon acetic acid fragments, which enter the Krebs
cycle
– Fatty Acid with even numbers of carbon atoms, produce
Propionyl-CoA, while fatty Acid with odd numbers of
carbon atoms, produce Acetyl-CoA

42
Lipid Metabolism

• Catabolism of fats
involves two
separate pathways
– Glycerol pathway
– Fatty acids pathway
43
Aktivasi asam lemak
transport asam lemak ke
matriks mitokondria
Mitochondria

47
Lipid Metabolism - Oxidation

• -Oxidation: a series of reactions that cleaves carbon atoms

two at a time from the carboxyl end of a fatty acid (C2-C3)
• The complete cycle of one -oxidation requires four enzymes
– Reaction 1: Oxidation of the , carbon-carbon single
bond to a carbon-carbon double bond
– Reaction 2: Hydration of the carbon-carbon double bond
– Reaction 3: Oxidation of the -hydroxyl group to a
carbonyl group
– Reaction 4: Cleavage of the carbon chain

49
50
Fatty Acid Metabolism - Efficiency

53
Lipogenesis and Lipolysis

• Lipolysis, the breakdown of stored fat, is

essentially lipogenesis in reverse
• Glucose is easily converted into fat since
acetyl CoA is:
– An intermediate in glucose catabolism
– The starting molecule for the synthesis of fatty
acids
• Excess dietary glycerol and fatty acids undergo
lipogenesis to form triglycerides

58
Lipogenesis and Lipolysis

59
Ketone • In humans and most other mammals, acetyl-CoA
formed in the liver during oxidation of fatty acids can
bodies either enter the citric acid cycle undergo conversion to
the “ketone bodies,” acetone, acetoacetate, and ß-
hydroxybutyrate, for export to other tissues.
• Acetone, produced in smaller quantities than the
other ketone bodies, is exhaled.
• Acetoacetate and ß-hydroxybutyrate are transported
by the blood to tissues other than the liver
(extrahepatic tissues), where they are converted to
acetyl-CoA and oxidized in the citric acid cycle,
providing much of the energy required by tissues such
as skeletal and heart muscle and the renal cortex.
• The brain, which preferentially uses glucose as fuel,
can adapt to the use of acetoacetate or ß-
hydroxybutyrate under starvation conditions, when
glucose is unavailable.
• The production and export of ketone bodies from the
liver to extrahepatic tissues allows continued
oxidation of fatty acids in the liver when acetyl-CoA is
not being oxidized in the citric acid cycle.
 Fatty Acid Biosynthesis
• Biosynthesis is not exact
reversal of oxidation

• Biosynthetic reactions
occur in the cytosol
 Fatty Acid Biosynthesis (Cont’d)
• Carboxylation of acetyl-CoA occurs in the cytosol
– Catalyzed by acetyl-CoA carboxylase
– Biotin is the carrier of the carboxyl group
– Malonyl-CoA is key intermediate that is produced
 Biosynthesis of Fatty Acid
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.
Biosynthesis of
Palmitate from
Acetyl- and
Malonyl-CoA
Sites of Fatty Acid Metabolism in an Animal Cell
• Acetyl-CoA is transported toSummary
the cytosol and converted to malonyl-CoA
• The biosynthesis of FA proceeds by the addition of 2-carbon units to the
hydrocarbon chain. The process is catalyzed by the fatty-acid synthase
complex

Comparison of FA Degradation and Biosynthesis

 Triacylglycerol Biosynthesis
• Lipids, such as,
triacylglycerols,
phosphoacylglyce
rols, and steroids
are derived from
FA and
metabolites of FA
Biosynthesis of Phosphoacylglycerols
Biosynthesis of sphingosine/Ceramide

• Require starting
materials palmitoyl-
CoA and serine
 Cholesterol Biosynthesis
• All carbon atoms of cholesterol and steroids
synthesized from it are derived from the two-
carbon acetyl group of acetyl-CoA

• Involves many reaction steps

• Involvement of isoprene units are key to the

biosynthesis of steroids and other
biomolecules known as terpenes
Overall View of Cholesterol
Biosynthesis
 Cholesterol Biosynthesis (Cont’d)
• Synthesis begins with the
condensation of two
molecules of acetyl-CoA
• Next, condensation with a
third molecule of acetyl-
CoA
• The formation of
mevalonate is completed
by reduction of the
thioester that gives a 1°
alcohol
 Mevalonate to Squalene
• The pyrophosphosphorylation of the 1° alcohol of mevalonate (two
moles of ATP) is followed by phosphorylation of the 3° alcohol (one
mole of ATP), then the concerted decarboxylation and -elimination
of phosphate ion gives isopentenyl pyrophosphate
• Then there is an enzyme-catalyzed isomerization of the carbon-
carbon double bond that gives dimethylallyl pyrophosphate
• Dimethylallyl pyrophosphate is then converted to isopentyl
pyrophosphate, which is followed by H+ loss to give farnesyl
pyrophosphate
• The joining together of two units of farnesyl pyrophosphate (C15)
units by a two-electron oxidation gives squalene (C30)
The Conversion of Mevalonate to
Squalene
 Cholesterol as a Precursor

• Cholesterol is the
precursor for a number of
steroid hormones
 Role of Cholesterol in Heart Disease
• Lipids are transported in the blood stream by
lipoproteins
• Cholesterol and its fatty acid esters are packaged
into several classes of lipoproteins for transport