LIPID METABOLISM

Biosynthesis of Fatty Acids

Fatty acids are synthesized by an
extramitochondrial system (cytosolic)
is present in many tissues :
Liver
Kidney
Brain
Lung
Mammary gland
Adipose tissue

Fatty Acid Synthase Multienzyme Complex

Production of Malonyl-CoA Is the Initial & Controlling

Step in Fatty Acid Synthesis

(acetyl-CoA carboxylase)

Control of Acetyl CoA Carboxylase

Biosynthesis of
Long-Chain Fatty Acids

PROSES DESATURASI
1. C 16
2. MULAI DARI C9
3. SELANJUTNYA SELISIH 3 C KEARAH -COOH

9 8 7

6 5 4

3 2 1

C-C-C-C-C-C-C=C-C-C=C-C-C=C-C-COOH

ASAM LEMAK ESENSIAL

- LINOLEAT

18

9, 12

- LINOLENAT

18

9, 12, 15

- ARACHIDONAT

18

5, 8, 11, 14

The Main Source

of NADPH
PPP
Malic enzyme
Isocitrate
dehydrogenase

Regulation of Fatty Acid Synthesis

Acetyl CoA carboxylase is the key control site in fatty acid synthesis.

Mobilization of Triacylglycerols

Utilization of Fatty Acids as Fuel

GLYCEROL METABOLISM

FATTY ACIDS ACTIVATION

acyl CoA synthetase

(also called fatty acid thiokinase)

FATTY ACIDS ACTIVATION

carnitine acyltransferase (also called

carnitine palmitoyl transferase I)

Acyl Carnitine Translocase

Overview of -oxidation of fatty acids

ATP
2ATP

AMP+PPi
2ADP+2Pi

2 ATP

3 ATP
(n 1) X 5 ATP

n X 12 ATP
(TCA cycle)

Reaction Sequence for the Degradation of Fatty Acids.

First Three Rounds in the Degradation of Palmitate

Two-carbon units are sequentially removed

from the carboxyl end of the fatty acid.

Principal reactions in fatty acid oxidation

An isomerase converts this double bond into a trans- D 2 double bond

Odd-Chain Fatty Acids Yield Propionyl Coenzyme A

succinyl CoA

(CYTRIC ACID CYCLE)

Propionyl CoA enters the citric acid cycle
after it has been converted into succinyl CoA.

Control of Fatty Acid Degradation

Malonyl CoA inhibits fatty acid degradation by

inhibiting the formation of acyl carnitine.

Overview of acylglycerol biosynthesis.

(PAF, platelet-activating factor.)

Synthesis and Degradation of Triacylglycerols by Adipose Tissue.

Major Metabolic Fates of Pyruvate and Acetyl CoA in Mammals

Formation of Ketone Bodies.

1)
2)
3)
4)

(HMG CoA)

3-ketothiolase
hydroxymethylglutaryl CoA synthase,
hydroxymethylglutaryl CoA cleavage enzyme
d-3-hydroxybutyrate dehydrogenase

Acetoacetate spontaneously decarboxylates to form acetone

Formation, utilization, and excretion of ketone bodies.

(The main pathway is indicated by the solid arrows.)

Utilization of Acetoacetate as a Fuel

Transport of ketone bodies from the liver and pathways of utilization and
oxidation in extrahepatic tissues.

Arachidonate Is the Major Precursor of Eicosanoid Hormones

Structures of Several Eicosanoids

Trans Fatty Acids Are Implicated in Various Disorders

Trans-unsaturated fatty acids are found in ruminant fat (eg, butter fat
has 27%), where they arise from the action of microorganisms in the rumen,
Main source in the human diet is from partially hydrogenated vegetable
oils (eg, margarine).
Trans fatty acids compete with essential fatty acids, exacerbate
essential fatty acid deficiency.
Structurally similar to saturated fatty acids, have comparable effects
in the promotion of hypercholesterolemia and atherosclerosis.

CHOLESTEROL IS DERIVED ABOUT EQUALLY FROM THE DIET

& FROM BIOSYNTHESIS
Acetyl-CoA Is the Source of All Carbon Atoms in Cholesterol

Step 1Biosynthesis of Mevalonate

Step 2Formation of Isoprenoid Units

Step 3Six Isoprenoid Units Form Squalene

Step 4Formation of Lanosterol

Step 5Formation of Cholesterol

Biosynthesis of
mevalonate.

6X

SQUALENE

LANOSTEROL

CHOLESTEROL

Transport of cholesterol between the tissues in humans.

CHOLESTEROL IS
EXCRETED FROM THE
BODY IN THE BILE AS
CHOLESTEROL OR
BILE ACIDS (SALTS)

Glycine
Taurine

Intestinal bacteria produce the

secondary bile acids.
Enterohepatic circulation 98-99%

Diet Can Play an Important Role in Reducing Serum Cholesterol

corn oil and sunflower seed oil : polyunsaturated and

monounsaturated fatty acids

olive oil : high concentration of monounsaturated fatty acids.

poly and monounsaturated
up-regulation of LDL receptors
catabolic rate of LDL
(LDL = the main atherogenic lipoprotein).

cholesterol

Four Major Groups of Plasma Lipoproteins

Have Been Identified

1. Chylomicrons : TG (intestinal absorption)

2. VLDL or pre--lipoproteins : TG (from the liver)
3. LDL or -lipoproteins : the catabolism of VLDL
4. HDL or -lipoproteins : in VLDL / chylomicron
metabolism and cholesterol transport.

Triacylglycerol is the predominant lipid in chylomicrons and VLDL

Cholesterol and phospholipid are the predominant lipids in LDL and HDL

Generalized Structure of A Plasma Lipoprotein

Composition of the lipoproteins in plasma of humans

1Secreted with chylomicrons but transfers to HDL.

2Associated with HDL2 and HDL3 subfractions.
3Part of a minor fraction known as very high density lipoproteins (VHDL).

Secretion of (A) chylomicrons

by an intestinal cell

Secretion of (B) very low

density lipoproteins by a
hepatic cell.
SD, space of Disse

Metabolic fate of chylomicrons

Metabolic fate of very low density lipoproteins (VLDL) and production of

low-density lipoproteins (LDL)

Metabolism of high-density lipoprotein (HDL) in reverse

cholesterol transport

LCAT, lecithin:cholesterol acyltransferase; C, cholesterol; CE, cholesteryl ester; PL,

phospholipid; A-I, apolipoprotein A-I; SR-B1, scavenger receptor B1; ABC-1, ATP binding
cassette transporter 1.

Imbalance in
the Rate of
Triacylglycerol
Formation &
Export Causes
Fatty Liver

Primary disorders of plasma lipoproteins (dyslipoproteinemias)

Hypolipidemic Drugs Will Reduce Serum Cholesterol& Triacylglycerol

Cholestyramine resin : bile acids reabsorption (small intestine)
bile acid synthesis (liver)
cholesterol excretion
up-regulates LDL receptors
plasma cholesterol.
Sitosterol : absorption of cholesterol from the gastrointestinal tract .
Statins : inhibit HMG-CoA reductase, thus up-regulating LDL receptors.
(atorvastatin, simvastatin, and pravastatin.)
Clofibrate and gemfibrozil : 1. VLDL secretion , plasma triacylglycerols .
2. stimulate hydrolysis of VLDL triacylglycerols by lipoprotein lipase.
Probucol : LDL catabolism , accumulation of oxidized LDL
Nicotinic acid : adipose tissue lipolysis , FFA , VLDL