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Elongation of Fatty Acids
Elongation of Fatty Acids
 Addition of 2 C units to 16 C Fatty acidAddition of 2 C units to 16 C Fatty acid
 Do not require multi enzyme fatty acidDo not require multi enzyme fatty acid
synthase complexsynthase complex
 Group of enzyme ELONGASE is requiredGroup of enzyme ELONGASE is required
 Reaction occur in: ER, Microsome andReaction occur in: ER, Microsome and
MitochondriaMitochondria
Microsomal Elongation of Fatty Acids
 Predominant mechanism for chain elongation
 Malonyl Co A --- donor of 2C
 Addition takes place on COOH terminal of FA
 Reactions are similar as synthesis in cytosol
Reactions for elongation
of FA
Microsomal fractionPalmitoyl COA
B- Keto acyl COA
B- OH acyl COA
Enoyl COA
Stearyl COA
Condensation
Reduction
Dehydrase
Reduction
Malonyl COA
CO2
NADPH
NADP
NADPH
NAD
P
H2O
C16
C2
C16 + 2
C18
Reactions for Mitochondial elongation
of FA
Acyl COA
B- Keto acyl COA
B- OH acyl COA
β Unsaturated acyl COA
Acyl COA
Condensation
Reduction
Dehydrase
Reduction
Acetyl COA
COA.SH
NADPH
NADP
NADPH
NADP
H2O
C16
C2
C16 + 2
C18
Rare
In matrix
Acetyl
CoA
2C donor
Reverse
of β
Oxidation
Synthesis of
Unsaturated Fatty acids
Synthesis of unsaturated FA
 Reaction for addition of unsaturation or
double bond in the existing fatty acid
chain with or without elongation
 Site :
Liver plays major role
 Requirements:
Acyl desaturase enzymes,
NADPH / NADH;
O2 and Oxygenase enzyme
Synthesis of unsaturated FA
 Enzymes: Acyl desaturase present
in Microsome
 Acyl desaturase is
Non heme iron containing
enzyme
Have broad specificity
Four different types
Add CIS double bond at C9
Steps of unsaturated FA synthesis
Mono unsaturated fatty acid Poly unsaturated fatty acid
Stearyl CoA
Oleyl CoA
O2 + NADPH
+ H+
2H2O +
NADP+
Microsomal desaturase
C 18:0
C 18:1 Δ9
Linoleyl CoAC 18:2 Δ9,12
Linolenoyl CoAC 18:3 Δ6,9,12
Δ6 desaturase
O2 + NADPH + H+
NADP+ + 2H2O
Ecosa trienoic acidC 20:3 Δ8,11,14
Elongation in
ER
Malonyl CoA
Arachidonyl CoA
C 20:4 Δ5,8,11,14
O2 + NADPH + H+
NADP+ + 2H2O
Δ5 desaturase
Storage
Lipogenesis
and
Utilization
Lipolysis
LIPIDS
TAG DAG MAG
FFA
GLYCEROL
LYPOGENESIS
Epinephrine
Glucagon Insulin
FFAFFA
Increases cAMP Decreases cAMP
Lipolgenesis : synthesis of TAG
from FFA and Glycerol
Acetyl CoA
Carboxylase 
CitrateLong chain
fatty acyl CoA
 
TA
G
DAG MAG
FFA
GLYCEROLLYPOLYSIS
HORMONE SENSITIVE
TRIGLYCERYL LIPASE
Epinephrine
Nor-epinephrine
Glucagon
Thyroxine
ACTH
Insulin
Niacin
Prostaglandins
FFAFFA
Increases cAMP Decreases cAMP
Lipolysis : degradation of TAG to FFA and
Glycerol

Synthesis of
Glycerophospholipids
COMPOUND LIPIDS
Biosynthesis of glycerophospholipid -1
Phosphatidic acid
Glycerol
Glycerol
Glucose
DHAP
Glycolysis
Glycerol –3-P
ATP ADP NADPHNADP+
Acetyl COA
COA.SH
Glycerol kinase Glycerol-3-P DH
Acyl transferase
1, acyl Glycerol –3-P
Acetyl COA
COA.SH
Acyl transferase
1,2, di acyl Glycerol –3-P
Phosphatidic acid
From Adipose tissue
in LIVER
in LIVER &
ADIPOSE
CO2
H2O
Biosynthesis of glycerophospholipid-2
H2O
Pi
1,2, di acyl Glycerol –3-P
Phosphatidic acid
Phosphatidate phosphatase
1,2, di acyl Glycerol
Acetyl COA
COA.SH
Acyl transferase
Tri acyl Glycerol
Choline
Phospho Choline
Phosphatidyl Choline
Lecithine
CPD -- Choline
ATP
ADP
Choline kinase
CTP
PPi
CMP
Phosphatidyl choline DAG transferase
Phosphocholine
cytidyl transferase
Biosynthesis of glycerophospholipid-3
H2O
Pi
1,2, di acyl Glycerol –3-P
Phosphatidic acid
Phosphatidate hydrolase
1,2, di acyl Glycerol
CO2
Phosphatidyl
ethanolamine
Phosphatidyl
Serine
CPD --DAG
CTP
Pi
CMP
Phosphatidyl serine
transferase
DAG-cytidyl
transferase
Serine
Phosphatidyl serine
decarboxylase
3 SAM
S adenosyl
homocystine
N mehtyl
transferase
Phosphatidyl Choline
Lecithine

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Fatty Acid Elongation and Unsaturation Processes

  • 2. Elongation of Fatty Acids  Addition of 2 C units to 16 C Fatty acidAddition of 2 C units to 16 C Fatty acid  Do not require multi enzyme fatty acidDo not require multi enzyme fatty acid synthase complexsynthase complex  Group of enzyme ELONGASE is requiredGroup of enzyme ELONGASE is required  Reaction occur in: ER, Microsome andReaction occur in: ER, Microsome and MitochondriaMitochondria
  • 3. Microsomal Elongation of Fatty Acids  Predominant mechanism for chain elongation  Malonyl Co A --- donor of 2C  Addition takes place on COOH terminal of FA  Reactions are similar as synthesis in cytosol
  • 4. Reactions for elongation of FA Microsomal fractionPalmitoyl COA B- Keto acyl COA B- OH acyl COA Enoyl COA Stearyl COA Condensation Reduction Dehydrase Reduction Malonyl COA CO2 NADPH NADP NADPH NAD P H2O C16 C2 C16 + 2 C18
  • 5. Reactions for Mitochondial elongation of FA Acyl COA B- Keto acyl COA B- OH acyl COA β Unsaturated acyl COA Acyl COA Condensation Reduction Dehydrase Reduction Acetyl COA COA.SH NADPH NADP NADPH NADP H2O C16 C2 C16 + 2 C18 Rare In matrix Acetyl CoA 2C donor Reverse of β Oxidation
  • 7. Synthesis of unsaturated FA  Reaction for addition of unsaturation or double bond in the existing fatty acid chain with or without elongation  Site : Liver plays major role  Requirements: Acyl desaturase enzymes, NADPH / NADH; O2 and Oxygenase enzyme
  • 8. Synthesis of unsaturated FA  Enzymes: Acyl desaturase present in Microsome  Acyl desaturase is Non heme iron containing enzyme Have broad specificity Four different types Add CIS double bond at C9
  • 9. Steps of unsaturated FA synthesis Mono unsaturated fatty acid Poly unsaturated fatty acid Stearyl CoA Oleyl CoA O2 + NADPH + H+ 2H2O + NADP+ Microsomal desaturase C 18:0 C 18:1 Δ9 Linoleyl CoAC 18:2 Δ9,12 Linolenoyl CoAC 18:3 Δ6,9,12 Δ6 desaturase O2 + NADPH + H+ NADP+ + 2H2O Ecosa trienoic acidC 20:3 Δ8,11,14 Elongation in ER Malonyl CoA Arachidonyl CoA C 20:4 Δ5,8,11,14 O2 + NADPH + H+ NADP+ + 2H2O Δ5 desaturase
  • 11. TAG DAG MAG FFA GLYCEROL LYPOGENESIS Epinephrine Glucagon Insulin FFAFFA Increases cAMP Decreases cAMP Lipolgenesis : synthesis of TAG from FFA and Glycerol Acetyl CoA Carboxylase  CitrateLong chain fatty acyl CoA  
  • 12. TA G DAG MAG FFA GLYCEROLLYPOLYSIS HORMONE SENSITIVE TRIGLYCERYL LIPASE Epinephrine Nor-epinephrine Glucagon Thyroxine ACTH Insulin Niacin Prostaglandins FFAFFA Increases cAMP Decreases cAMP Lipolysis : degradation of TAG to FFA and Glycerol 
  • 14. Biosynthesis of glycerophospholipid -1 Phosphatidic acid Glycerol Glycerol Glucose DHAP Glycolysis Glycerol –3-P ATP ADP NADPHNADP+ Acetyl COA COA.SH Glycerol kinase Glycerol-3-P DH Acyl transferase 1, acyl Glycerol –3-P Acetyl COA COA.SH Acyl transferase 1,2, di acyl Glycerol –3-P Phosphatidic acid From Adipose tissue in LIVER in LIVER & ADIPOSE CO2 H2O
  • 15. Biosynthesis of glycerophospholipid-2 H2O Pi 1,2, di acyl Glycerol –3-P Phosphatidic acid Phosphatidate phosphatase 1,2, di acyl Glycerol Acetyl COA COA.SH Acyl transferase Tri acyl Glycerol Choline Phospho Choline Phosphatidyl Choline Lecithine CPD -- Choline ATP ADP Choline kinase CTP PPi CMP Phosphatidyl choline DAG transferase Phosphocholine cytidyl transferase
  • 16. Biosynthesis of glycerophospholipid-3 H2O Pi 1,2, di acyl Glycerol –3-P Phosphatidic acid Phosphatidate hydrolase 1,2, di acyl Glycerol CO2 Phosphatidyl ethanolamine Phosphatidyl Serine CPD --DAG CTP Pi CMP Phosphatidyl serine transferase DAG-cytidyl transferase Serine Phosphatidyl serine decarboxylase 3 SAM S adenosyl homocystine N mehtyl transferase Phosphatidyl Choline Lecithine