LIPID METABOLISM GUT FAT GLUCOSE G U T CATABOLISM BIOSYNTHESIS STORAGE (LIVER) Cell Membrane nyl-C ADIPOCYTE .34 lo o Cytosol 1.1 a 3. A M FATTY ACID SYNTHASE FAT ACYL-CoA Acyl- (2.3.1.86) FATTY 6.2.1.3 2.3.1.7 Includes all the of TRIACYLGLYCEROL ACIDS Multi- complex ro CH OCOR pop tein 2 Carnitine HSCoA Fatty Acid Synthesis except Acetyl-CoA carboxylase Li s R'CO.OCH CH2OCOR" Adrenaline rm Palmitoyl-ACP CH Insulin to fo 3[CH Carnitine HSCoA es 2CH 2.3.1.20 nc 2 ] ue CO 3.1.1.3 q 8 S 3.1.1.28 e C CH OCOR S o L 2 Acyl- A R'CO.OCH 6 i CH2OCOR e carnitine CH2OH equ nce p R'CO.OCH S s o Diacylglycerol CH2OH n CH CH CH .CO.S-ACP CH3[CH2CH2]nCH2CH2CO.S-ACP CH [CH CH ] CH CH CO.S-ACPp Diacylglycerol 3 2 2 3 2 2 n 2 2 CH3[CH2CH2]nCH2CH2CO.S-CoA r 3.1.3.4 CH3CH2CH2.CO.S-CoA Butanoyl-ACP Hexanoyl-ACP ACYL-ACP o 3.1.1.34 ACYL-CoA Butanoyl-CoA t CH2OCOR e R'CO.OCH + + + NADP NADP NADP i CH2O-P Ubiquinone n Phosphatidate CH2OH (UQ) 1.3.1.10 1.3.1.10 1.3.1.10 R'CO.OCH 1.3.99.3 1.3.99.2 + + + NADPH+H NADPH+H NADPH+H CH2OH Ubiquinol 2.3.1.15 Monoacyl- (UQH ) CH2OH 2.3.1.51 glycerol 2 HOCH CH [CH CH ] CH=CH.CO.S-CoA CH [CH CH ] CH=CHCO.S-ACP CH [CH CH ] CH=CHCO.S-ACP CH2OP 3 2 2 n CH3CH=CH.CO.S-ACP 3 2 2 n 3 2 2 n CH3CH2CH2CH=CH.CO.S-CoA Butenoyl-ACP Hexenoyl-ACP 3-Enoyl-ACP Glycerol-3-P 3-Enoyl-CoA Butenoyl-CoA CH2OH HOCH 3.1.1.23 4.2.1.17 H2O H2O H2O CH OP 1.1.1.8 CH2OH 4.2.1.55 CO2 L 4.2.1.58 4.2.1.59 Glycerol i H O CH2OH 2 H O 4.2.1.61 p 2 H2O Di-OH- o acetone-P p CH3[CH2CH2]nCH(OH)CH2CO.S-ACP RCO-SCoA r CH [CH CH ] CH(OH)CH .CO.S-CoA CH [CH CH ] CH(OH)CH CO.S-ACP o 3 2 2 n 2 CH3CH(OH)CH2CO.S-ACP 3-OH- 3 2 2 n 2 (Glycolysis) ACYL-CoA CH3CH(OH)CH2CO.S-CoA 3-OH-Acyl-ACP t 3-OH-Acyl-CoA 3-OH-Butanoyl-CoA 3-OH- Hexanoyl-ACP RCOO- e Butanoyl-ACP i 6.2.1.3 FATTY GLUCOSE n + + + NAD + NADP NADP ACIDS NADP - 1.1.1.157 1.1.1.100 RCOO 1.1.2.11 1.1.1.100 1.1.1.100 Insu +

+ + l FATTY ACIDS NADH+H

i + NADPH+H n

NADPH+H NADPH+H

3.1.1.34

Lipoprotein

CH [CH CH ] COCH .CO.S-CoA

CH COCH CO.S-ACP CH [CH CH ] COCH CO.S-ACP CH [CH CH ] COCH CO.S-ACP 3 2 2 n 2 3 2 3 2 2 n 2

3 2 2 n 2 L CH COCH CO.S-ACP ipoprotein 3 2 3-Oxo- Acetoacetyl-ACP 3-Oxoacyl-ACP 3-Oxoacyl-CoA I Acetoacetyl-CoA Hexanoyl-ACP n n CO CO s u l i 2.3.1.16 CO2 2 2 2.3.1.9 HSACP HSACP 2.3.1.41 HSACP

2.3.1.41 2.3.1.41 GLUCOSE CO2 ACETYL-CoA -OOCCH2CO.SACP ATP

Malonyl-ACP 3.6.1.34 CH3CO.SACP Acetyl-ACP HSCoA 2.3.1.39 Oxaloacetate CO2 DPH+H + HS.ACP A NADPH+H+ Pyruvate N Pentose Pyruvate Malate Phosphate HSCoA 1.1.1.40 ATP+CO 6.4.1.1 Citrate Pathway + 2 NADH+H+ 2.3.1.38 NADP -OOCCH CO . S C o A Committed HSACP 2 Malate ADP+Pi Fumarate Malon y l - C o A to Lipid + Isocitrate NAD Oxaloacetate UQH B i osynthesis 1.1.1.37 2 + Ubiquinol Insulin NADH+H UQ ADP+Pi Adrenaline Oxaloacetate H2O Oxoglutarate Succinate Citrate 6.4.1.2 CO2 ADP+Pi HSCoA 4.1.3.7 Acyl-CoA 4.1.3.8 HSCoA Succinyl-CoA ATP ATP 2.3.1.39 Citrate Citrate - 2.3.1.9 ACETYL-CoA Acetyl-CoA CH2COO CH C(OH)CH COSCoA CH3COCH2CO.S-CoA 3 2 CH COCH COSCoA Acetoacetyl-CoA 3 2 4.1.3.5 Acetoacetyl-CoA 3-OH-3-methyl- 6.4.1.1 glutaryl-CoA 4.1.3.5 NADPH+H+ 4.1.3.4 (HMG) CH2COO- CH COO- 2 - CH3C(OH)CH2COSCoA CH C(OH)CH CH OH HO CH COCH CH3COCH2COO CH CH(OH)CH COO 3 2 2 3 3 4.1.1.4 3 2 3-OH-3-methylglutaryl-CoA (HMG) Mevalonate Acetone Acetoacetate 1.1.1.30 3-OH-Butyrate 1.1.1.34 CHOLESTEROL Committed to Cholesterol Mitochondrial inner membrane

- Biosynthesis KETONE BODIES

Brain Skeletal & Heart Muscle Renal Cortex (In starvation)

TCA Acetoacetyl-CoA 3-OH-Butyrate ATP CYCLE Acetyl-CoA Acetoacetate KETONE BODIES

+ + ANABOLISM 8CH3CO.SCoA + 14NADPH +14H +7ATP CH3[CH2CH2]7CO.SCoA+ 14NADP +7HSCoA+ 7ADP+7Pi Acetyl-CoA Palmitoyl-CoA + CATABOLISM CH [CH CH ] CO.SCoA + 7Ubiquinone + 7H O + 7NAD + + 7HSCoA 8CH CO.SCoA +7 Ubiquinol +7NADH +7H 3 2 2 7 2 3 Palmitoyl-CoA 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 1.1.1.8 Glycerol-3-P- dehydrogenase 1.3.1.10 E noyl-[ACP]-reductase 2 . 3 .1.51 1 -Acylglycerol-3-P O-acyl 4.1.3.5 OH-Methylglutaryl-CoA synthase 1.1.1.34 HMG-CoA reductase 1.3.99.2 Butyryl-CoA dehydrogenase 4.1.3.7 C itrate synthase 1.1.1 3-OH-acyl-CoA dehydrogenase1.3.99.3 A cyl-CoA dehydrogenase 3 . 1 .1.3 T riacylglycerol lipase 4 . 1 . 3 . 8 A TP Citrate .35 4.2 1.1.1.37 Malate dehydrogenase 2.3.1.7 C arnitine- O-acyltransferase 3.1.1.23 A cylglycerol lipase . 1 . 1 7 E noyl-CoA hydratase 1.1.1.40 Malate dehydrogenase 2.3.1.9 A cetyl-CoA-C-acetyl transferase 3.1.1.28 A cylcarnitine 4 . 2 . 1 . 5 5 3 -OH-Butyryl-CoA dehydratase 2.3.1.15 G lycerol-3-P O-acyl transferase 3 . 1 .1.34 L ipoprotein lipase 4 . 2 . 1 . 5 8 C rotonyl-[ACP] hydratase ( oxaloacetate 4.2.1.59 3-OH-octanoyl-[ACP] dehydratase 1.1.1.100 3-Oxoacyl-[ACP] 2.3.1.16 A cetyl-CoA C-acyl t r ansferase 3 . 1 .3.4 Phosphatidate 2.3.1.20 D iacylglycerol O-acyl transferase 4 .1.1.4 A cetoacetate decarboxylase 4 . 2 . 1 . 6 1 3 - OH-Palmitoyl-[ACP] dehydratase 1.1.1.157 3-OH-butyryl-CoA 6.2.1.3 Long-chain-fatty.-acid-CoA 1.1.1.211 Long-chain 3-OH-acyl-CoA 2.3.1.38 [ ACP] S-acyl transferase 4 . 1 .1.9 M alonyl-CoA decarboxylase 2.3.1.39 [ A C P] S-malonyl transferase 4.1.3.4 6.4.1.1 Pyruvate carboxylase 1.2.4.1 Pyruvated ehydrogenase OH-Methylglutaryl-CoA lyase 6.4.1.2 Acetyl-CoA carboxylase

0502 Designed by Donald Nicholson c 2002 IUBMB