Lipid metabolism

metabolism of lipids

1. LIPID METABOLISM
Mrs.D.M.Kulkarni,
Assistant Professor,
Yash Institute of Pharmacy,
Aurangabad

2. Contents
Lipid metabolism
•β-Oxidation of saturated fatty acid (Palmiticacid)
•Formation and utilization of ketonebodies;
ketoacidosis
•De novo synthesis of fatty acids (Palmiticacid)
•Biological significance of cholesterol and conversion of
cholesterol into bile acids, steroid hormone and
vitamin D
•Disorders of lipid metabolism: Hypercholesterolemia,
atherosclerosis, fatty liver and obesity

3. What is a Lipid?
These are nonpolarorganic compounds
Generally insoluble to water, but soluble to nonpolarsolvent like;
-Chloroform -Acetone –ether -benzene
It contains a carbonyl group (-COOH)
What are the functions of lipids?
As membrane structural component.
As intracellular storage depot of metabolic fuel.
As transport form of metabolic fuel.
As protective form of the cells of many bacteria,
leaves of higher plants, exoskeleton of insects
and the skin of vertebrates.
A regulatory substances.
As transport form of some neurotransmitters.
As receptors in nerve ending membranes.
As determinants of immunological specificity.
Enzyme co-factors

5. Types of Lipids
The four main groups of lipids include:
1. Fatty acids (saturated and unsaturated)
2. Glycerides(glycerol-containing lipids)
3. Nonglyceridelipids (sphingolipids, steroids, waxes)
4. Complex lipids (lipoproteins, glycolipids)
Triglyceride degradation
Triglycerides are degraded by lipases to form free fatty acids and glycerol

9. Lipid Catabolism
Catabolism –refers to several reactions that
produce energy
-it is a breakdown of complex
organic compounds into a simpler compounds.
It is related to carbohydrate metabolism because
the carbohydrates will turn into fats. The
glycerol will participate is glycolysis.
It is important process because the produced
Fatty acids will participate in fatty acid
oxidation.
Energy is produced through a process called
lipogenesis

11. Lipid Catabolism
Fats are important source of energy as (1gm of fat gives 9 kcal energy).
• Mainly as triacylglycerols(triglycerides) inadiposecells
• Constitute 84% of stored energy
• Protein -15%
• Carbohydrate (glucose or glycogen) -<1%
Beta Oxidation of Fatty Acid
The break down of a fatty acid to acetyl-CoA.
The end product of each cycle is the fatty acid shortened by 2
carbons and acetyl CoA.
The series of reactions is also known as the betaoxidation
pathway because the major reaction site is the beta-carbon or #3
carbon from the thioestercarbon.
Happens in the mitochondrial membrane
The fatty acids must be activated and turned into acetyl-CoA
• Process is strictly aerobic
• After production Acetyl-CoAis fed directly into the Krebs cycle

12. It occurs in many tissues including liver, kidney and heart.
• Fatty acids oxidation doesn't occur in the brain
o There are several types of fatty acids oxidation.
(1) β-oxidation of fatty acid
(2) α-oxidation of fatty acids
(3) ω-oxidation of fatty acids
• The beta oxidation of fatty acids involve three stages:
1.Activation of fatty acids in the cytosol
2.Transport of activated fatty acids into mitochondria
(carnitineshuttle)
3.Beta oxidation proper in the mitochondrial matrix

13. 1) Activation of FA:
This proceeds by FA thiokinase(acylCOAsynthetase) present in
cytosolThiokinaserequires ATP, COA SH, Mg++. The product of this
reaction is FA acylCOA and Water

15. 2-Transport of fatty acylCoAfrom cytosolinto mitochondria:
• Long chain acylCoAtraverses the inner mitochondria membrane
with a special transport mechanism called Carnitineshuttle.

16. (rate-limitingstep)
1.AcylgroupsfromacylCOAistransferredtocarnitinetoformacyl
carnitinecatalyzedbycarnitineacyltransferaseI,intheouter
mitochondrialmembrane.
2.Acylcarnitineisthenshuttledacrosstheinnermitochondrial
membranebyatranslocaseenzyme.
3.TheacylgroupistransferredbacktoCoAinmatrixbycarnitineacyl
transferaseII.
4.Finally,carnitineisreturnedtothecytosolicsidebytranslocase,in
exchangeforanincomingacylcarnitine

18. 3. Proper of β –oxidation in the mitochondrial matrix
There are 4 steps in β –oxidation
Step I –Oxidation by FAD linked dehydrogenase
Step II –Hydration by Hydratase
Step III –Oxidation by NAD linked dehydrogenase
Step IV –ThiolyticclevageThiolase

19. The first reaction is the oxidation of acylCoAby
an acylCoAdehyrogenaseto give α-β unsaturartedacylCoA(enoyl
CoA).FAD is the hydrogen acceptor

20. The second reaction is the hydration of the double bond to β-
hydroxyacylCoA(phydroxyacylCoA).

21. The third reaction is the oxidation of β-
hydroxyacylCoAto produce β-KetoacylCoAa NAD-dependent
reaction

22. • The fourth reaction is cleavage of the two carbon
fragment by splitting the bond between α and β carbons
• By thiolaseenzyme

23. The release of acetyl CoAleaves an acylCoA
molecule shortened by 2 carbons.
• This acylCoAmolecule is the substrate for the
next round of oxidation starting with acylCoA
dehydrogenase.
• Repetition continues until all the carbons of
the original fatty acylCoAare converted to acetyl
CoA.
• In the last round a four carbon acylCoA
(butyrylCoA) is cleaved to 2 acetyl CoA

24. Energeticsof FA oxidation
e.g. Palmitic (16C):
1.β-oxidation of palmitic acid will be repeated 7 cycles producing
8 molecules of acetyl COA.
2.In each cycle FADH2 and NADH+H+ is produced and will be
transported to the respiratory chain.
• FADH2 2 ATP
• NADH + H+ 3 ATP
• So 7 cycles 5x7 = 35 ATP
3. Each acetyl COA which is oxidized in citric cycle gives
12 ATP (8 x 12 = 96 ATP)
4. 2 ATP are utilized in the activation of fatty acid (It occurs once).
• Energy gain = Energy produced -Energyutilized
• = 35 ATP + 96 ATP -2 ATP = 129 ATP