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Lipid Metabolism
Lipid Metabolism
ACETYL-CoA
CO2
Ketone Bodies
Lipid Anabolism(Biosynthesis)
Sphingolipids
Phospholipids Triglycerides
General Triglyceride Catabolism
- Fatty acids in triglycerides (TG) are the major
source of energy in the body. TG are stored in
adipocytes or are found in dietary fat.
- 40% of daily energy requirement of people in
industrial countries is met with TG.
- Main tissues using fatty acids as energy source are
liver, heart and resting skeletal muscle
- A 70kg male has about 7 kg of lipid. A 65 kg
female has about 14 kg of lipid.
This is adequate energy needs for about a
month of starvation.
-There are carbohydrate stores for only
about a day.
-Carbohydrate and protein yield about 4 kcal
energy/g, whereas, triglycerides yield about 9
kcal of energy/g.
- Excess dietary carbohydrate is converted into
TG.
cyclic AMP
stimulates protein kinase
ATP ADP
glycerol–3-phosphate
glycerol NAD + NADH
glycerol phosphate
dehydrogenase
NADH NAD +
CH2OPO3 _
glycolysis O
CH2OH
dihydroxyacetone phosphate
Lehn fig 17-4 modified
*Fatty Acid Catabolism*
Fatty Acid Activation
Fatty acids enter the cell as the free fatty
acid and must be activated into a fatty
acyl CoA to enable subsequent metabolism.
O O
2. RCO-P-O-adenosine + CoASH
O- O
AMP RC-SCoA +AMP
fatty acyl CoA
Transport of Fatty Acids
into the Mitochondrion
♦ Fatty acids are stored in cytosol. Fatty acids
must be transported into the mitochondria,
where oxidative metabolism occurs.
carnitine
Carnitine Acyl Transferase I and II
3. oxidation to ketone
4. thiolysis releasing
acetyl-CoA and
shortened
(by two) acyl-CoA
-Oxidation (cont’d) C16
propionyl-CoA carboxylase
CO2 + ATP [biotin]
O_
odd chain O O O _O O
acetone
Ketone O
O
Bodies CH3 C CH2
O
acetoacetate
OH
O
CH3 CH CH2
O
-hydroxybutyrate
Ketogenesis
1. condensation of two
acetyl-CoAs
4a. decarboxylate
to acetone
(normally
small amounts)
4b. reduce
Fate of Ketone Bodies
BLOOD
♦ It is highly regulated
inactivated by phosphorylation (favored by glucagon)
activated by dephosphorylation (favored by insulin)
citrate also increases the activity allosterically
Fatty Acid Synthase and Acyl Carrier
Protein
- Chain elongation occurs with fatty acid bound to a
carrier protein, acyl carrier protein, (ACP), which has
a prosthetic group related to CoASH.
O O
|| ||
CH3C-SCoA + ACPSH CH3C-S-ACP +CoASH
malonyl-SCoA + ACPSH malonyl–S-ACP +
CoASH
Fatty Acid Synthase
- Fatty acid synthase is a complex of enzymes that
adds C2 units to a growing fatty acid chain.
-It is a cyclic process that occurs with the fatty acid
covalently attached to ACP and requires reductive
reactions that use NADPH.
a) pyruvate dehydrogenase
b) breakdown of fatty acids
c) catabolism of ketogenic amino acids
NAD+ NAD+
malate malate
Citrate-Malate Shuttle
Citrate is the carrier of acetyl groups from the
mitochondrion to the cytosol. This is accomplished by
the action of citrate synthase and citrate lyase.
O O O
C O_ C O _ ATP ADP
C O_
Acetyl-CoA
O C O CH2 O C
C CH CH2
CH2 _O
CH2 Acetyl-CoA C
C
O O_ C O O_
oxaloacetate (OAA) citrate
O O _ oxaloacetate
Fatty acyl-CoA synthetase (thiokinase) uses ATP & CoA to activate fatty acids
Citrate synthase & citrate lyase produces acetyl-CoA carrier in mit &
releases acetyl CoA in cytosol