LÍPIDOS

Ácidos gordos - reserva de energia, percursores de outros lípidos

Acilglicerois - intermediários metabólicos
Fosfoglicerídeos - componentes de membranas
Eicosanoides - moduladores celulares
Esfingolípidos - componentes de membranas
Terpenos - precursores de esteroides, vitaminas, etc
Esteroides - componentes de membranas, hormonas e vitaminas
 LIPID BIOSYNTHETIC NETWORKS

SPHINGOLIPIDS GLYCEROPHOSPHOLIPIDS GLYCEROLIPIDS

FATTY ACIDS
EICOSANOIDS STEROLS

Acetyl CoA

PRENOLS

Isopentenyl-PP E. Fahy 2010 ©

 Síntese de ácidos gordos
In the United States population, 30% of adults are obese and another 35% are overweight.
Obesity is defined in terms of body mass index (BMI): BMI weight in kg/(height in m)2. A BMI
below 25 is considered normal; 25 to 30 is overweight, and greater than 30, obese.
Obesity is life-threatening. It significantly increases the chances of developing type II diabetes
as well as heart attack, stroke, and cancers of the colon, breast, prostate, and endometrium.
Consequently, there is great interest in understanding how body mass and the storage of fats
in adipose tissue are regulated. ■

To a first approximation, obesity is the result of taking in more calories in the diet than are
expended by the body’s energy-consuming activities. The body can deal with an excess of
dietary calories in three ways:
(1) convert excess fuel to fat and store it in adipose tissue,
(2) burn excess fuel by extra exercise,
(3) “waste” fuel by diverting it to heat production (thermogenesis) in uncoupled mitochondria.

In mammals, a complex set of hormonal and neuronal signals act to keep fuel intake and energy
expenditure in balance, so as to hold the amount of adipose tissue at a suitable level.
Metabolism and Energy Overview
• Many biomolecules are
Carbo- degraded to Acetyl CoA
Proteins Lipids
hydrates • Acetyl CoA provides
biologic energy
• Excess acetyl CoA is
Amino Simple Fatty stored as Fatty Acids
(FA’s)
Acids Sugars Acids
• FA’s are assembled into
more complex lipids like
triglycerides (TG’s)
Pyruvate

Energy
Acetyl CoA (CO2, H2O)

E.A. DENNIS 2010 ©

Common Saturated Fatty Acids
Saturated FA’s have no double bonds

16 Carbons = Palmitic Acid (Palmitate)

18 Carbons = Stearic Acid (Stearate)

E.A. DENNIS 2010 ©

Common Unsaturated Fatty Acids
Unsaturated FA’s have at least one double bond,
usually in the Z (cis) conformation

18 Carbons, 1 double bond at c9 = Oleic Acid (Oleate)

18 9 1

18 Carbons, 2 double bonds at c9 and c12 = Linoleic Acid (Linoleate)

18 12 9 1

E.A. DENNIS 2010 ©

More Unsaturated Fatty Acids
18 Carbons, 3 cis double bonds at 9, 12 & 15 =
a-Linolenic Acid (a-Linolenate)

18 15 12 9 1

20 Carbons, 4 cis double bonds at 5,8,11 & 14

Arachidonic Acid (Arachidonate)

(5Z,8Z,11Z,14Z-Eicosatetraenoic Acid)
E.A. DENNIS 2010 ©
 Síntese de ácidos gordos
. Não é o processo inverso da oxidação
. Envolve enzimas diferentes
. Requer a participação de um intermediário 3C

Forma-se a partir de
acetil-CoA numa
reacção irreversível
catalisada pela acetil-
CoA carboxilase
Key Enzyme: Acetyl-CoA Carboxylase
• Acetyl-CoA Carboxylase is
a key enzyme
• Converts acetyl-CoA into
malonyl-CoA
– The CO2 is released
later
– Biotin is a cofactor
• It is the “committed step”
in FA synthesis
• It is the regulated, rate-
limiting enzyme in FA
synthesis
“E” above is the enzyme acetyl-CoA
carboxylase, which is conjugated to biotin.

E.A. DENNIS 2010 ©

 Síntese de ácidos gordos
. É catalisada pela sintase dos ácidos gordos (FAS)

. Envolve gasto de NADPH

. Ciclos sucessivos com adição de uma molécula de

malonil-CoA resultando no aumento do tamanho da
cadeia de 2C por ciclo, com perda de uma molécula
de CO2
 Sintase dos ácidos gordos
. Duas classes – FASI e FASII

. FASI – vertebrados e fungos – sete actividades

enzimáticas num único complexo; um único produto
de 16C

. FASII – bactérias e plantas (mitocôndria de

vertebrados) – sistema dissociado; produtos de
diferentes tamanhos
Estrutura da FASI de Porco

KS- β-ketoacyl-ACP
synthase

MAT –
malonyl/acetyl-
CoA—ACP
transferase

DH - β-hydroxyacyl-
ACP dehydratase

ER - enoyl-ACP
reductase

KR - β-ketoacyl-ACP
reductase

ACP - acyl carrier

protein

TE - thioesterase
Estrutura da FASI do fungo Thermomyces lanuginosus
Fatty Acid Synthesis Summary
One iteration:
Step 1: Set up acetyl-ACP

Step 2: Set up malonyl-ACP

Step 3: Condense them, giving Acetoacetyl ACP

Step 4: Use NADPH to reduce distal carbonyl to a hydroxyl group

Step 5: Remove the hydroxyl group as H 2O leaving a double bond

Step 6: Use another NADPH to reduce the double bond

REPEAT: From step 2 using the new 4-carbon butyryl-ACP in

place of acetyl-ACP in step 3

E.A. DENNIS 2010 ©

 Produção de uma molécula de ácido palmitico (C16)

7 Acetil-CoA + 7CO2 + 7ATP è 7 malonil-CoA + 7ADP + 7Pi

Acetil-CoA + 7 malonil-CoA + 14NADPH + 14H+ è

palmitato + 7CO2 8 CoA + 14NADP + 6H2O
+

8 Acetil-CoA + 7ATP + 14NADPH + 14H+ è

palmitato + 8 CoA + 7ADP + 7Pi + 14NADP + 6H2O