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Study Material
on
Lipid Metabolism
Presented By:
Ms. Sayali Dilip Powar
(M. Pharm )
Department of Pharmaceutical Chemistry,
@ Tatyasaheb Kore College of Pharmacy, Warananagar
26/03/2020
1
Content
• β-Oxidation of saturated fatty acid (Palmitic
acid)
• Formation and utilization of ketone bodies;
ketoacidosis
• Disorders of lipid metabolism:
Hypercholesterolemia, atherosclerosis, fatty
liver and obesity
26/03/2020 2
β-Oxidation of saturated fatty acid
• The fatty acids in the body are mostly oxidized
by BETA oxidation.
• Oxidation may be defined as the oxidation of
fatty acids on the beta carbon atom.
• This results in the sequential removal of a
two carbon fragment, acetyl CoA.
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β-Oxidation of saturated fatty acid
• 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
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NOTE
• Fatty acids are oxidized by most of the tissues
in the body. However, brain, erythrocytes and
adrenal medulla cannot utilize fatty acids for
energy requirement.
26/03/2020 5
Fatty acid oxidation-
Stages and tissues
• The beta oxidation of fatty acids involves three
stages
• I. Activation of fatty acids occurring in the
cytosol
• II. Transport of fatty acids into mitochondria
• III.beta-Oxidation proper in the mitochondrial
matrix.
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Diagram: β-Oxidation 3 Stages
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β-oxidation of fatty acid
• β-oxidation of fatty acid- The break down of a
fatty acid to acetyl-CoA.
• Occurs in the mitochondria
• Process is strictly aerobic
• After production Acetyl-CoA is fed directly into the
Krebs cycle
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Diagram: β-Oxidation of saturated fatty acid
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Diagram: β-Oxidation of saturated fatty acid26/03/2020 10
Formation and utilization of ketone
bodies; ketoacidosis
• Ketone bodies, or simply ketones are substances
produced by the liver during gluconeogenesis a process
which creates glucose in times of fasting and
starvation.
• There are three ketone bodies produced by the liver.
• They are acetoacetate, beta-hydroxybutyrate,
and acetone.
• These compounds are used in healthy individuals to
provide energy to the cells of the body when glucose is
low or absent in the diet.
• In a normal man, concentration of ketone bodies in the
blood is usually less than 3 mg/100ml
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Acetoacetate, acetone and β- hydroxybutyrate are
collectively known as ketonebodies
Formation and utilization of ketone
bodies; ketoacidosis
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• Ketone bodies are the water-soluble
molecules containing the ketone group that
are produced by the liver from fatty acids
during periods of low food intake,
carbohydrate restrictive diets, starvation,
prolonged intense exercise, alcoholism, or in
untreated type 1 diabetes mellitus.
Formation of ketone bodies
26/03/2020 13
The major pathway of ketone bodies utilization is Transacylase pathway.
1.Formation of acetoacetate from β-hydroxybutyrate
• β-hydroxybutyrate is converted to acetoacetate by β-hydroxybutyrate
dehydrogenase.
2. Formation of acetoacetyl CoA
• Acetoacetate is activated to form acetoacetyl CoA by the transfer of
CoA molecule from succinyl CoA.
• The reaction is catalyzed by succinyl CoA:Acetoacetate CoA
transferase
3. Formation of acetyl CoA
• Acetoacetyl CoA is cleaved to form acetyl CoA and acetyl CoA in a
reaction catalyzed by thiolase
Utilization of ketone bodies
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Utilization of ketone bodies
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• Ketoacidosis is a metabolic state caused by
uncontrolled production of ketone bodies that
cause a metabolic acidosis.
ketoacidosis
26/03/2020 16
Disorders of Lipid Metabolism
• Hypercholesterolemia
• Fatty liver
• Obesity
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Hypercholesterolemia/
High Cholesterol
Excess of cholesterol in the
bloodstream.
26/03/2020 18
WHAT HAPPENS IF CHOLESTEROL IS HIGH
26/03/2020 19
26/03/2020 20
CHOLESTEROL FUNCTIONS
1) Structural component of cell membrane
2) Precursor for synthesis of steroids in body
TYPES OF CHOLESTEROL
1) HDL- Highly Desirable Lipoprotein (GOOD)
2) LDL- Lethally Dangerous Lipoprotein (BAD)
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26/03/2020 22
CONTROL OF HIGH CHOLESTEROL
1. Consumption of PUFA
2. Dietary cholesterol
3. Dietary fiber
4. Lifestyle
5. Use of drugs
26/03/2020 23
OBESITY
• Obesity is essentially an excessive
accumulation of triacylglycerols in fatty tissue
• A triglyceride (TG, triacylglycerol, TAG, or
triacylglyceride) is an ester derived from
glycerol and three fatty acids (from tri- and
glyceride).
• Triglycerides are the main constituents of
body fat in humans and other vertebrates, as
well as vegetable fat.
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FATTY LIVER
26/03/2020 28
What is fatty liver disease?
• Liver is the largest organ inside body.
• It helps your body digest food, store energy,
and remove poisons.
• Fatty liver disease is a condition in which fat
builds up in your liver.
26/03/2020 29
Types
• There are two main types:
1. Nonalcoholic fatty liver disease (NAFLD)
2. Alcoholic fatty liver disease
26/03/2020 30
What is nonalcoholic fatty liver
disease (NAFLD)?
• Fatty liver disease that is not related
to heavy alcohol use.
• There are two kinds:
• Simple fatty liver, in which you have fat in your
liver but little or no inflammation or liver cell
damage.
• Nonalcoholic steatohepatitis (NASH), in which
you have inflammation and liver cell damage, as
well as fat in your liver. Inflammation and liver
cell damage can cause fibrosis, or scarring, of the
liver. NASH may lead to cirrhosis or liver cancer.
26/03/2020 31
26/03/2020 32

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LIPID METABOLISM PART 1

  • 1. Study Material on Lipid Metabolism Presented By: Ms. Sayali Dilip Powar (M. Pharm ) Department of Pharmaceutical Chemistry, @ Tatyasaheb Kore College of Pharmacy, Warananagar 26/03/2020 1
  • 2. Content • β-Oxidation of saturated fatty acid (Palmitic acid) • Formation and utilization of ketone bodies; ketoacidosis • Disorders of lipid metabolism: Hypercholesterolemia, atherosclerosis, fatty liver and obesity 26/03/2020 2
  • 3. β-Oxidation of saturated fatty acid • The fatty acids in the body are mostly oxidized by BETA oxidation. • Oxidation may be defined as the oxidation of fatty acids on the beta carbon atom. • This results in the sequential removal of a two carbon fragment, acetyl CoA. 26/03/2020 3
  • 4. β-Oxidation of saturated fatty acid • 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 26/03/2020 4
  • 5. NOTE • Fatty acids are oxidized by most of the tissues in the body. However, brain, erythrocytes and adrenal medulla cannot utilize fatty acids for energy requirement. 26/03/2020 5
  • 6. Fatty acid oxidation- Stages and tissues • The beta oxidation of fatty acids involves three stages • I. Activation of fatty acids occurring in the cytosol • II. Transport of fatty acids into mitochondria • III.beta-Oxidation proper in the mitochondrial matrix. 26/03/2020 6
  • 7. Diagram: β-Oxidation 3 Stages 26/03/2020 7
  • 8. β-oxidation of fatty acid • β-oxidation of fatty acid- The break down of a fatty acid to acetyl-CoA. • Occurs in the mitochondria • Process is strictly aerobic • After production Acetyl-CoA is fed directly into the Krebs cycle 26/03/2020 8
  • 9. Diagram: β-Oxidation of saturated fatty acid 26/03/2020 9
  • 10. Diagram: β-Oxidation of saturated fatty acid26/03/2020 10
  • 11. Formation and utilization of ketone bodies; ketoacidosis • Ketone bodies, or simply ketones are substances produced by the liver during gluconeogenesis a process which creates glucose in times of fasting and starvation. • There are three ketone bodies produced by the liver. • They are acetoacetate, beta-hydroxybutyrate, and acetone. • These compounds are used in healthy individuals to provide energy to the cells of the body when glucose is low or absent in the diet. • In a normal man, concentration of ketone bodies in the blood is usually less than 3 mg/100ml 26/03/2020 11
  • 12. Acetoacetate, acetone and β- hydroxybutyrate are collectively known as ketonebodies Formation and utilization of ketone bodies; ketoacidosis 26/03/2020 12
  • 13. • Ketone bodies are the water-soluble molecules containing the ketone group that are produced by the liver from fatty acids during periods of low food intake, carbohydrate restrictive diets, starvation, prolonged intense exercise, alcoholism, or in untreated type 1 diabetes mellitus. Formation of ketone bodies 26/03/2020 13
  • 14. The major pathway of ketone bodies utilization is Transacylase pathway. 1.Formation of acetoacetate from β-hydroxybutyrate • β-hydroxybutyrate is converted to acetoacetate by β-hydroxybutyrate dehydrogenase. 2. Formation of acetoacetyl CoA • Acetoacetate is activated to form acetoacetyl CoA by the transfer of CoA molecule from succinyl CoA. • The reaction is catalyzed by succinyl CoA:Acetoacetate CoA transferase 3. Formation of acetyl CoA • Acetoacetyl CoA is cleaved to form acetyl CoA and acetyl CoA in a reaction catalyzed by thiolase Utilization of ketone bodies 26/03/2020 14
  • 15. Utilization of ketone bodies 26/03/2020 15
  • 16. • Ketoacidosis is a metabolic state caused by uncontrolled production of ketone bodies that cause a metabolic acidosis. ketoacidosis 26/03/2020 16
  • 17. Disorders of Lipid Metabolism • Hypercholesterolemia • Fatty liver • Obesity 26/03/2020 17
  • 18. Hypercholesterolemia/ High Cholesterol Excess of cholesterol in the bloodstream. 26/03/2020 18
  • 19. WHAT HAPPENS IF CHOLESTEROL IS HIGH 26/03/2020 19
  • 21. CHOLESTEROL FUNCTIONS 1) Structural component of cell membrane 2) Precursor for synthesis of steroids in body TYPES OF CHOLESTEROL 1) HDL- Highly Desirable Lipoprotein (GOOD) 2) LDL- Lethally Dangerous Lipoprotein (BAD) 26/03/2020 21
  • 23. CONTROL OF HIGH CHOLESTEROL 1. Consumption of PUFA 2. Dietary cholesterol 3. Dietary fiber 4. Lifestyle 5. Use of drugs 26/03/2020 23
  • 24. OBESITY • Obesity is essentially an excessive accumulation of triacylglycerols in fatty tissue • A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from tri- and glyceride). • Triglycerides are the main constituents of body fat in humans and other vertebrates, as well as vegetable fat. 26/03/2020 24
  • 29. What is fatty liver disease? • Liver is the largest organ inside body. • It helps your body digest food, store energy, and remove poisons. • Fatty liver disease is a condition in which fat builds up in your liver. 26/03/2020 29
  • 30. Types • There are two main types: 1. Nonalcoholic fatty liver disease (NAFLD) 2. Alcoholic fatty liver disease 26/03/2020 30
  • 31. What is nonalcoholic fatty liver disease (NAFLD)? • Fatty liver disease that is not related to heavy alcohol use. • There are two kinds: • Simple fatty liver, in which you have fat in your liver but little or no inflammation or liver cell damage. • Nonalcoholic steatohepatitis (NASH), in which you have inflammation and liver cell damage, as well as fat in your liver. Inflammation and liver cell damage can cause fibrosis, or scarring, of the liver. NASH may lead to cirrhosis or liver cancer. 26/03/2020 31