LIPID METABOLISM

GUT BIOSYNTHESIS
FATTY ACID SYNTHASE (2.3.1.86)
(LIVER) Cell Membrane Cytosol

FAT GLUCOS

Ma

STORAGE ADIPOCYTE

GUT
1.1 3.
.3 4

CATABOLISM
lonyl-C
2.3.1.7

oA

FAT
oprotein Lip
TRIACYLGLYCEROL
CH2OCOR R'CO.OCH CH2OCOR"

Multi-enzyme complex Includes all the enzymes of Fatty Acid Synthesis except Acetyl-CoA carboxylase
orm Palmitoyl-ACP CH3 [CH s to f 2 CH nce 2] C ue 8 OS eq C S

ACYL-CoA FATTY ACIDS 6.2.1.3

Carnitine

HSCoA

Acylcarnitine

2.3.1.20

Adrenaline Insulin
3.1.1.3

L i p o CH3CH2CH2.CO.S-ACP CH3[CH2CH2]nCH2CH2CO.S-ACP CH3[CH2CH2]nCH2CH2CO.S-ACPp r Butanoyl-ACP ACYL-ACP Hexanoyl-ACP o t e + + + i NADP NADP NADP n 1.3.1.10
oA

Carnitine
3.1.1.28

HSCoA

Diacylglycerol
3.1.3.4

CH2OCOR R'CO.OCH CH2OH

Diacylglycerol
3.1.1.34

CH2OCOR R'CO.OCH CH2OH

CH3[CH2CH2]nCH2CH2CO.S-CoA

quence Se s

Acylcarnitine

1.3.1.10

1.3.1.10

Phosphatidate
CH2OH HOCH CH2OP
2.3.1.15 2.3.1.51

CH2OCOR R'CO.OCH CH2O-P

ACYL-CoA
1.3.99.3

CH3CH2CH2.CO.S-CoA

Butanoyl-CoA
1.3.99.2

NADPH+H

NADPH+H

NADPH+H

CH2OH R'CO.OCH CH2OH

Ubiquinone

(UQ)

Monoacylglycerol
CH2OH HOCH 3.1.1.23 CH2OH

Ubiquinol

(UQH2)

CH3CH=CH.CO.S-ACP

Butenoyl-ACP

CH3[CH2CH2]nCH=CHCO.S-ACP

Hexenoyl-ACP
H 2O

CH3[CH2CH2]nCH=CHCO.S-ACP

3-Enoyl-ACP

Glycerol-3-P
CH2OP CO CH2OH
1.1.1.8

CH3[CH2CH2]nCH=CH.CO.S-CoA CH3CH2CH2CH=CH.CO.S-CoA

3-Enoyl-CoA
4.2.1.17

Butenoyl-CoA
4.2.1.55

H 2O
4.2.1.58

H 2O
4.2.1.59 4.2.1.61

Glycerol

H 2O

Di-OHacetone-P ACYL-CoA
6.2.1.3
RCO-SCoA

CH3CH(OH)CH2CO.S-ACP

CH3[CH2CH2]nCH(OH)CH2CO.S-ACP

3-OHButanoyl-ACP
NADP
1.1.1.100

3-OHHexanoyl-ACP

CH3[CH2CH2]nCH(OH)CH2CO.S-ACP

3-OH-Acyl-ACP
+ +

(Glycolysis)

+ +

NADP
1.1.1.100

+ +

GLUCOSE
Ins

NADP

1.1.1.100

NADPH+H

NADPH+H

NADPH+H

FATTY ACIDS
3.1.1.34 Lipoprotein lipase

RCOO-

FATTY ACIDS

RCOO-

L i p o p r o t e i n

H 2O

H 2O

CH3[CH2CH2]nCH(OH)CH2.CO.S-CoA CH3CH(OH)CH2CO.S-CoA

3-OH-Acyl-CoA

3-OH-Butanoyl-CoA
NAD +

1.1.2.11

1.1.1.157

NADH+H+

ulin

Acetoacetyl-ACP
CO2 HSACP
2.3.1.41

CH3COCH2CO.S-ACP

CH3[CH2CH2]nCOCH2CO.S-ACP

CO2 HSACP
2.3.1.41 2.3.1.41

3-OxoHexanoyl-ACP

CH3[CH2CH2]nCOCH2CO.S-ACP

3-Oxoacyl-ACP

Lip o protein

CO2 HSACP

3-Oxoacyl-CoA
2.3.1.16

CH3[CH2CH2]nCOCH2.CO.S-CoA CH3COCH2CO.S-ACP
2.3.1.9

Acetoacetyl-CoA

s u li

GLUCOSE
-OOCCH2CO.SACP

CO2

ACETYL-CoA

ATP
3.6.1.34

Acetyl-ACP
HSCoA
2.3.1.38

CH3CO.SACP

Malonyl-ACP
DPH+H + NA Pentose
Phosphate Pathway

HSCoA 2.3.1.39 HS.ACP

NADPH+H+
NADP +

CO2

Oxaloacetate

Pyruvate

Pyruvate
ATP+ CO2 ADP+Pi 6.4.1.1

1.1.1.40

Citrate

Malate NADH+H+

HSACP

Malonyl-CoA
Insulin Adrenaline Citrate Acyl-CoA
2.3.1.9

-OOCCH2CO.SCoA

Committed to Lipid Biosynthesis

Malate

ADP+Pi
6.4.1.2

+ NAD 1.1.1.37 + NADH+H ADP+Pi

Oxaloacetate
H2 O HSCoA 4.1.3.7

Isocitrate

Fumarate
UQ Succinate
Ubiquinol

UQH2

CO2 ATP
2.3.1.39

Oxaloacetate
4.1.3.8 ATP HSCoA

Oxoglutarate

Succinyl-CoA

ACETYL-CoA

Citrate

Citrate

Acetyl-CoA
4.1.3.5 4.1.3.4

Acetoacetyl-CoA
4.1.3.5

CH3COCH2CO.S-CoA

CH2COOCH3C(OH)CH2COSCoA

Acetoacetyl-CoA
NADPH+H+
CH2COOCH3C(OH)CH2CH2OH

CH3COCH2COSCoA

3-OH-3-methylglutaryl-CoA (HMG)
-

CH2COOCH3C(OH)CH2COSCoA

3-OH-3-methylglutaryl-CoA (HMG)

6.4.1.1

1.1.1.34

Mevalonate

Committed to Cholesterol Biosynthesis

CHOLESTEROL

HO

Acetone

CH3COCH3

4.1.1.4

Acetoacetate 1.1.1.30 3-OH-Butyrate

Mitochondrial inner membrane

CH3COCH2COO-

CH3CH(OH)CH2COO

KETONE BODIES

Skeletal & Heart Muscle

TCA CYCLE

Renal Cortex

Brain (In starvation)

ATP

Acetyl-CoA

Acetoacetyl-CoA

Acetoacetate

3-OH-Butyrate

KETONE BODIES

ANABOLISM
CATABOLISM

8CH3CO.SCoA + 14NADPH +14H++7ATP

CH3[CH CH2] CO.SCoA + 7Ubiquinone + 7H2O + 7NAD++ 7HSCoA 2 7

Acetyl-CoA

CH3[CH2CH2]7CO.SCoA+ 14NADP++7HSCoA+ 7ADP+7Pi

Palmitoyl-CoA

Palmitoyl-CoA

8CH3CO.SCoA +7 Ubiquinol +7NADH +7H

Acetyl-CoA

COMPLETE (AEROBIC) OXIDATION OF PALMITOYL CoA

CH3[CH2CH2]7CO.SCoA + 23O2 + ~ (106 ADP + 106Pi) 16CO2 + 119 H2O + HSCoA + ~106ATP

This is a fascinating equation which explains how some animals, such as camels and polar bears can survive in the most adverse environments They can use fat ,not only as the sole source of energy, but also of water. The killer whale cannot utilise sea-water but creates its own from fat
ENZYMES Glycerol-3- P-dehydrogenase 1.3.1.10 Enoyl-[ACP]-reductase 1.3.99.2 Butyryl-CoA dehydrogenase HMG-CoA reductase 3-OH-acyl-CoA dehydrogenase 1.3.99.3 Acyl-CoA dehydrogenase 2.3.1.7 Carnitine-O-acyltransferase Malatedehydrogenase 2.3.1.9 Acetyl-CoA-C-acetyl transferase Malatedehydrogenase 2.3.1.15 Glycerol-3-P O-ac yl transferase (oxaloacetate 2.3.1.16 Acetyl-CoA C-acyl transferase 1.1.1.100 3-Oxoacyl-[ACP] 2.3.1.20 DiacylglycerolO-acyl transferase 1.1.1.157 3-OH-butyryl-CoA 2.3.1.38 [ACP] S-acy l transferase 1.1.1.211 Long-chain 3-OH-acyl-CoA [ACP] S-malonyl transferase 2.3.1.39 1.2.4.1 Pyruvatedehydrogenase

1.1.1.8 1.1.1.34 1.1.1.35 1.1.1.37 1.1.1.40

2.3.1.51 1-Acylglycerol-3-P O-acyl transferase 3.1.1.3 Triacylglycerol lipase 3.1.1.23 Acylglycerol lipase 3.1.1.28 Acylcarnitine hydrolase 3.1.1.34 Lipoprotein lipase 3.1.3.4 Phosphatidate phosphatase 4.1.1.4 Acetoacetate decarboxylase 4.1.1.9 Malonyl-CoA decarboxylase 4.1.3.4 OH-Methylglutaryl-CoA lyase

4.1.3.5 4.1.3.7 4.1.3.8 4.2.1.17 4.2.1.55 4.2.1.58 4.2.1.59 4.2.1.61 6.2.1.3 6.4.1.1 6.4.1.2

OH-Methylglutaryl-CoA synthase Citrate synthase ATP Citrate lyase Enoyl-CoA hydratase 3-OH-Butyryl-CoA dehydratase Crotonyl-[ACP] hydratase 3-OH-octanoyl-[ACP] dehydratase 3-OH-Palmitoyl-[ACP] dehydratase Long-chain-fatty.-acid-CoA ligase Pyruvate carboxylase Acetyl-CoA carboxylase

0502

Designed by Donald Nicholson

c 2002 IUBMB