Lipids Presentaion

METABOLISM OF
FATTY ACIDS,
CHOLESTEROL &
LIPOPROTEINS
PRESENTATION SUBMITTED
TO:
Dr. RIFFAT BATOOL
PRESENTATION SUBMITTED
GROUP MEMBERS
NAMES & TOPICS
  – Oxidation Of FA {SHAHIQ-UL-HASSAN}
(20 – ARID – 2333)
 TCA Cycle {FATIMA SHAKEEL}
(20 – ARID – 2310)
 Biosynthesis Of FA {AFSHA MUKHTAR}
(20 – ARID – 2294)
 Cholesterol Metabolism {ANEEZA IQBAL}
(20 – ARID – 2297)
 Lipoprotein Metabolism {WALEED ABDULLAH}
(20 – ARID – 2338)
OUTLINES
1) Metabolism Of Fatty Acids

2) Metabolism Of Cholesterol
3) Metabolism Of Lipoproteins
METABOLISM
OF FATTY
Fatty
Acids …
 Consists of the long hydrocarbon chains & the
terminal carboxylic group
 Hydrocarbon chain may be saturated (with no
double bonds) or unsaturated (with double bonds)
 Are fuel molecules that can be stored as
triglycerides
 Fatty acids derivatives serves as hormones &
intracellular messengers e.g.; prostaglandins, steroids
FATTY ACID
DEGRADATION
 Fatty acid oxidation is the mitochondrial aerobic
process of breaking down a fatty acid into acetyl – CoA
units
Types based on nomenclature
1. Beta () Oxidation {Mitochondria}
2. Alpha () Oxidation {ER / Peroxisome}
3. Omega () Oxidation {ER / Microsomes}
4. Oxidation of unsaturated fatty acid chain
{Mitochondria}
5. Oxidation of very long chain fatty acid <20, 22
carbons {Peroxisomes}
 - Oxidation Of
Fatty Acids
(Prominent
 Most of the fatty acids in the body are oxidized by 
Principle Pathway):
- oxidation of fatty acids
 It is defined as “Oxidation of fatty acids at  -
Carbon”
 This results in sequentially removed of 2 carbon
units, acetyl CoA
 There are 3 main steps of  - oxidation of fatty
acids as;
o Activation of fatty acids (In Cytosol)
o Transport of fatty acids into mitochondria
o  - oxidation proper (In Mitochondrial matrix)
a) Activation Of Fatty
Acids:
 The 1st step of oxidation of fatty acids is the
activation of free fatty acids
 It is must to activate fatty acids before
catabolized
 In this reaction, fatty acid is converted to acyl
– CoA in cytosol by the enzyme thiokinase (acyl
CoA synthetase) in presence of ATP, coenzyme A
 The reaction occurs in 2 steps
b) Transport Of Acyl CoA To
Inner Mitochondrial
Membrane:
 Fatty acyl CoA is impermeable to the inner
mitochondrial membrane, so it is carried in the
form of fatty acyl carnitine
 Fatty acyl carnitine is transported across the
inner mitochondrial membrane in exchange for
carnitine by an antiport translocase
c)  - Oxidation
Proper:
 Fatty acid β – oxidation is the process by which

fatty acids are broken down to produce energy
 The long – chain acyl – CoA can then enter the
fatty acid β – oxidation pathway, resulting in the
production of one acetyl – CoA from each cycle of
β-oxidation
 This acetyl – CoA then enters the TCA cycle
Conclusion

Net Gain
o 1 Acetyl CoA
o 1 FADH2
o 1 NADH, H2O
TCA Cycle
(Tricarboxylic Acid
Cycle:)
 Also known as the citric acid cycle or the
krebs cycle
 Having series of chemical reactions to
release stored energy through the oxidation of
acetyl CoA derived from carbohydrates, fats
and proteins
 In eukaryotic cells, its occur in the matrix of
mitochondrion and in bacteria its occur in
cytosol
 The cycle involves the oxidation of acetyl
CoA to CO2 and H2O
 It is the central metabolic pathway
 Occur in many steps
 Discovered by Hans Kreb’s in 1937
BIOSYNTHESIS OF
FATTY ACIDS
De Novo
Synthesis
 Occurs in liver, kidney, adipose tissues
 Enzymes are located in cytosomal fraction of the cell
 It is called as “extramitochondrial” or “cytoplasmic
fatty acid synthase system”
 It takes place in cytoplasm of the cell
 The major fatty acid synthesized de novo is palmitic
acid, the 16 – C saturated fatty acid
o Source of carbon atoms → Acetyl CoA
o Source of Source of reducing equivalents → NADPH
o Source of energy → ATP
Steps In De Novo
Fatty Acid
a) Production Synthesis
(Transport)
Of Acetyl CoA & NADPH:
 Acetyl CoA is produced in mitochondria by,
oOxidation of pyruvate
oOxidation of fatty acids
 However, mitochondria is not permeable for acetyl
CoA
 So, an alternate arrangement is made for the
transfer of acetyl CoA to cytosol in the form of citrate
 Acetyl CoA condenses with oxaloacetate in
mitochondria to form citrate
 Citrate is free transported to cytosol
 Here in cytosol, citrate is cleaved by citrate lyase
to acetyl CoA & oxaloacetate
 Oxaloacetate in cytosol is converted to malate
 Malate dehydrogenase converts malate to
pyruvate with production of NADPH & CO2
 Transport of acetyl CoA from mitochondria to
cytosol is coupled with the production of NADPH &
CO2, both of them are utilized for FA synthesis
b) Conversion Of Acetyl
CoA To Malonyl CoA:
 Acetyl CoA is carboxylated to malonyl CoA by

acetyl CoA carboxylase.
 ATP dependent & Biotin is required for CO2
fixation.
 Acetyl CoA carboxylase is the regulatory enzyme
in this pathway.
c) Reactions Of FAS
(Fatty Acid Synthase
Complex):
 The 2 C fragment of acetyl CoA is transferred to ACP
of FAS, by the enzyme acetyl tranacylase
o Acetyl unit is then transferred to cysteine – SH of
the enzyme
o Thus ACP site falls vacant
 The enzyme malonyl transacylase transfer
malonate from malonyl CoA to ACP to form acetyl –
malonyl enzyme
 Now, FAS has 2 groups attached to it
 an acetyl group to cysteine – SH & malonyl group to
ACP – SH
 Enzyme complex is now ready for chain elongation
process
1) Condensation 
 Acetyl group which is attached to cysteine – SH is
condenses with malonyl group attached to ACP to form  –
ketoacyl – ACP by losing CO2 which was added by
carboxylase
 This reaction is catalysed by ketoacyl synthase
2) Reduction 
 Ketoacyl reductase reduces ketoacyl group to
hydroxyacyl group
 The reducing equivalents are supplied by NADPH
3) Dehydration 
  – hydroxyacyl – ACP undergoes dehydration by the
enzyme dehydratase to form enoyl – ACP
4) Reduction 
 Enoyl – ACP reduced by enzyme enoyl reductase to acyl –
ACP
 The carbon chain attached to ACP is
transferred to cys – SH
 The reaction of 2 – 6 are repeated 6 times
 Each time, the FA is elongated by 2 C unit
 At the end of 7 cycles, a 16 C FA (saturated)
is formed at ACP
 The enzyme thioesterase separates
palmitate from fatty acid synthase
 This complete fatty acid synthesis
Conclusion

Net Gain
o 6 NADH2
o 2 FADH2
o 2 ATP molecules
METABOLIS
M OF
CHOLESTR
CHOLESTER
OL …
 Cholesterol is a waxy light yellow crystalline solid &
has 27 C – atoms
 Contains cyclopentano perhydro phenanthrene
ring
 Animal and plant food contain sterols but only animal
food contains cholesterol
 Needed to make bile, sex hormones, steroids &
vitamin D
 It is the constituent of cell membrane structure
 Dietary recommendations → <300 mg/d
 Enzymes which synthesized cholesterol are partly
located in endoplasmic reticulum and partly located in
cytoplasm.
BIOSYNTHESIS OF
 About 1g (~CHOLESTEROL
70%) of cholesterol is synthesized per day in
adults
 Remaining ~ 30% comes from the dietary intake like, egg
yolk, liver, shellfish, meat etc
 The largest contribution is made by,
oLiver (50%)
oIntestine (15%)
oSkin
oAdrenal cortex
oReproductive tissues
 For production of 1 mol of cholesterol
o18 moles of Acetyl CoA
o36 moles of ATP
o16 moles of NADPH
are required
Regulation Of Cholesterol
Synthesis
HMG – CoA
 IsReductase
the rate limiting enzyme in cholesterol synthesis
 HMGR (Hydroxy – 3 – methylglutaryl – CoA reductase)
catalyzes the committed step in cholesterol synthesis
 Consists of a single polypeptide chain
Controlled by HMG – CoA reductase
1) Feedback Control
2) Hormonal Control
3) Inhibition by Drugs
4) Inhibition by Bile acids
5) Fasting Condition
DEGRADATION OF
CHOLESTEROL
Cholesterol undergo degradation reactions in the
humans with the conversion of cholesterol to the
physiologically important products like,
1) Formation
Of Bile Acids
 The primarily important bile acids are,
oCholic Acids
oChenodeoxy Cholic Acids
 Synthesized in the liver from the cholesterol in the
multi – step pathways
 The primary bile acids are conjugated with glycine
& taurine to form,
o Glycocholic acid
o Taurocholic acid
o Glycochenodeoxycholic acid
o Taurochenodeoxycholic acid
BILE ACID
SYNTHESIS
2) Steroid
Hormones
Cholesterol is the precursor for synthesizing all the
five classes of steroid hormones like,
 GLUCOCORTICOID  e.g.; Cortisol
 MINERALOCORTICOID  e.g.;
Aldosterone
 PROGESTINS  e.g.; Progesterone
 ANDROGENS  e.g.; Testosterone
 ESTROGENS  e.g.; Estradiol

3)
Vitamin
D
7 – Dehydrocholestrol, an intermediate of the
biosynthetic pathway of cholestrol, is
converted into cholecalciferol (vitamin D3) by
ultra violet rays in the skin.
METABOLISM
OF
LIPOPROTEI
NSmacromolecular
 Spherical … assembly containing the
lipids and the specific proteins.
 Consists of esterified and unesterified cholesterol,
triglycerides, phospholipids and apolipoproteins. The
proteins function as cofactors and ligands for
receptors.
Classification Of
Lipoproteins
Classified into four types
1) Chylomicrons
2) VLDL (Very Low density Lipoprotein)
3) LDL (Low Density Lipoprotein)
4) HDL (High Density Lipoprotein)
5) IDL (Intermediate Density Lipoprotein)
EXOGENOUS
PATHWAY
Chylomicron
Processing
 Chylomicron come through our diet
 Transported from mouth to intestine
 Then from intestine to plasma
 HDL donates Apo C2 and Apo E
 Then transported to blood capillaries
 Here, Apo C2 activates lipoprotein lipase
 Lipase breaks triglyceride into the glycerol
and the fatty acids
 Glycerol is metabolized through glycolysis
while rest of chylomicron moves toward liver
 In liver it undergoes endocytosis and changes
into various vitamins, amino acids and
cholesterol
ENDOGENOUS
PATHWAY
Metabolism Of
VLDL, HDL & LDL
 VLDL is produced in the liver
 Transported to plasma
 Then towards blood capillaries
 Here, triglyceride is break down and
remaining part is called IDL
 IDL is converted to LDL which is metabolized
in tissues through endocytosis
HDL
 It is formed in the blood

 Peripheral tissues transfer cholesterol ester
to it and it is converted into HDL3
 Further, transfer of more cholesterol esters
form HDL2
 HDL2 then shares cholesterol esters with
VLDL and also liver where it is metabolized

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METABOLISM OF

1) Metabolism Of Fatty Acids

 Fatty acid β – oxidation is the process by which

 Acetyl CoA is carboxylated to malonyl CoA by

Controlled by HMG – CoA reductase

 GLUCOCORTICOID  e.g.; Cortisol

 PROGESTINS  e.g.; Progesterone

 ANDROGENS  e.g.; Testosterone

 ESTROGENS  e.g.; Estradiol

 It is formed in the blood

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