Lipids

• Triglyceride ; Storage form of energy

 Lipids

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• Stored in adipose tissue

• Protects internal organs by providing a cushioning effect

APPLE TYPE OBESITY

• Excess fat on the abdomen

• Common in men
• Android type
• Significant correlation with metabolic syndrome
 PEAR TYPE OBESITY

• Excess fat on the things and buttocks

• Common in women
• Gynoid type
• Not significant correlation with metabolic
syndrome
 Truncal Obesity

• Contributes to Metabolic syndrome and

Cardiovascular diseases
• A risk factor for heart attack
• Abnormality in lipid metabolism leads to
Atherosclerosis
• Saturated fatty acids do not contain DOUBLE BOND
• Unsaturated fatty acids contain 1 or more DOUBLE BONDS
 Butyric Acid
No Double Bond Solid
 Oleic Acid
Contains Double Bond Liquid
Monounsaturated Fatty Acids
Contain 1 double bond

• Palmitooleic acid; 16 C, Body fat

• Oleic acid; 18 C, Body fat
• Erusic acid; 22 C, Mustard oil,
• Nervonic acid; 24 , Brain lipids
Polyunsaturated Fatty Acids (= PUFA )
Contain more than 1 double bond

• Linoleic acid; 18 (2) , Vegetable oils

• Linolenic acid; 18 (3) , Vegetable oils
• Arachidonic acid; 20 (4) , Vegetable oils
 Arachidonic acid; 20(4)

• PUFA
• Contains 20 C and 4 double bond
 ‘’Arachidonic acid derivatives’’

• Prostaglandins , Thromboxanes, Leukotrienes

• Physiologically and pharmacologically active compounds
• Act as local hormones
• Leukotrienes cause bronchoconstriction and play a part in
Asthma
 ‘’Arachidonic acid derivatives’’
• Prostaglandins; Mediate pain sensitivity and
inflammation
• Thromboxanes; Involved in blood clotting and
constriction of arteries
• Leukotrienes; Attract White Blood Cells and
involved inflammatory diseases such as Asthma ,
Arthritis
• Anti inflammatory, Antipyretic, Analgesic actions
are related to inhibit Prostaglandin synthesis
• An antithrombogenic effect
• Prevents formation of blood clots that could occlude heart
vessels
• Inhibits Cyclooxygenase enzyme in platelets so;
• Inhibits Thromboxane A2 synthesis by through irreversible
Acetylation
• Inhibits platelet activation and Vasoconstriction
Omega 3 and Omega 6 Fatty Acids
 Omega 3 Fatty Acids

• Anti-Inflammatory effects
• Promote the synthesis of less inflammatory prostaglandins
and leukotrienes as compared to ω6 fatty acids
• Alpha Linolenic Acid (ALA) in plant oils
• Eicosapentaenoic Acid (EPA) in fish oil
• Docosahexaenoic Acid (DHA) in fish and algal oils
 Omega 3 Fatty Acids

• Diets rich in ω3 fatty acids are beneficial

• Particularly for cardiovascular disease
• Also for other chronic degenerative diseases such as cancer,
rheumatoid arthritis, and Alzheimer disease
 ESSENTIAL FATTY ACIDS

• Linoleic acid, Linolenic acid, Arachidonic acid

• We don’t have necessary enzymes to make them
• Must be supplied by diet
 Essential Fatty Acids

• Linoleic acid; 18 (2) , Vegetable oils

• Linolenic acid; 18 (3) , Vegetable oils
• Arachidonic acid; 20 (4) , Vegetable oils
 Double bonds can show Cis- or Trans İzomerism

• Cis- unsaturated fatty acid; Hydrogens on the same side

• Trans- unsaturated fatty acid; H on the opposite side
• Most naturally occurring unsaturated fatty acids have cis
double bonds
• Double bonds in naturally occurring unsaturated long-chain
fatty acids are nearly all in the cis configuration, the
molecules being bent 120° at the double bond
• Oleic acid has a V shape, whereas Elaidic acid remains
straight
 Trans fatty acids

• By-product of saturation of fatty acids during hydrogenation

of natural oils in margarine production
• Consumption of trans fatty acids is associated with
increased risk of cardiovascular disease and diabetes
 DIETARY LIPIDS
• Triglyceride ( Triacylglycerol )
• Phospholipids
• Free fatty acids
• Cholesterol
• Ester Cholesterol ( Fatty acid bound to Cholesterol)
 Cholesterol
• Widely distributed in all cells of the body but particularly in
nervous tissue
• A structural component of all cell membranes, modulating
their fluidity
• Major constituent of plasma lipoproteins
• Often found as Cholesteryl ester, where the hydroxyl group
on position 3 is esterified with a long-chain fatty acid
• Occurs in animals but not in plants
• A precursor of Bile acids, Steroid hormones, and Vitamin D
 Cholesterol

• A gradual deposition of cholesterol in the tissues,

particularly in the endothelial linings of blood vessels leads
to plaque formation
• Causes the narrowing of blood vessels (Atherosclerosis) and
• Increased risk of Cardio-, Cerebro-, and Peripheral vascular
diseases
• Blood is watery, Lipids are fatty
• To transport lipids in blood stream
• Needs to carry in small packages called Lipoproteins
 PLASMA LIPOPROTEINS

• Chylomicrons
• Very Low Density Lipoproteins (VLDL)
• Low Density Lipoproteins (LDL)
• High Density Lipoproteins (HDL)
 Lipoproteins

• Chylomicrons contain so little protein and so much

Triglyceride that they are the lowest in density
• Very Low Density Lipoproteins= VLDL; are half Triglycerides
• Low Density Lipoproteins = LDL; are half cholesterol
• High Density Lipoproteins= HDL; are half protein,
accounting their high density
 Lipoproteins play a key role in

• Absorption and transport of dietary lipids by the small

intestine
• Transport of lipids from the liver to peripheral tissues
• Transport of lipids from peripheral tissues to the liver
(= Reverse cholesterol transport)
 Lipoproteins; Chylomicrons

• Synthesis; In intestine
• Transport; Exogenous ( Diet derived ) Triglycerides
to peripheral tissues
 Lipoproteins; VLDL

• Synthesis; In liver
• Transport; Endogenous (= Synthesized in liver )
Triglycerides to peripheral tissues
 Lipoproteins; LDL

• Synthesis; In blood circulation from VLDL

• Transport; Cholesterol esters to peripheral tissues
 Lipoproteins; HDL

• Synthesis; In liver
• Transport; Excess cholesterol from tisues to liver
 FATTY ACIDS SYNTHESIS
‘’Lipogenesis’’
• A large proportion of Fatty acids used by the body is
supplied by Diet
• Carbohydrates and proteins obtained from Diet in excess
of the body’s needs can be converted to Fatty acids
• Fatty acids are stored as Triglyceride
 Lipogenesis necessitates
• Substrate; Acetyl CoA
• Cofactors; NADPH, ATP, Mn2+, Biotin
• Source of CO2; HCO3
• End product; Palmitate (= Palmitic acid) ( A free fatty acid )
Pentose phosphate pathway and Malic
Enzyme Provide NADPH for Lipogenesis
 KETONE BODIES

• Acetoacetate,
• 3-Hydroxybutyrate (Known as β-Hydroxybutyrate),
• Acetone (Nonmetabolized side product)
• Liver Mitochondria have the capacity to convert
Acetyl CoA derived from Fatty acid oxidation into
Ketone bodies
 Acetoacetate and β-Hydroxybutyrate
• Organic acids
• Transported in blood to peripheral tissues
• In peripheral tissues can be reconverted to Acetyl
CoA, which can be oxidized by Krebs cycle
 Ketone bodies are Important sources of
Energy for Peripheral tissues because;
• They are soluble in aqueous solution
• Therefore, do not need to be incorporated into
Lipoproteins or carried by Albumin as do the other lipids
• They are produced in Liver during periods when amount of
Acetyl CoA present exceeds Oxidative capacity of Liver
• They are used in proportion to their concentration in the
blood by extrahepatic tissues, such as Skeletal and Cardiac
muscle, Intestinal mucosa, and Renal cortex
 KETOGENESIS
Synthesis of Ketone bodies by Liver
• During fasting;
• Liver is flooded with Fatty acids
mobilized from Adipose tissue
(Lipolysis)
• Results elevated Hepatic Acetyl CoA
produced by fatty acid oxidation
 KETOGENESIS IN LIVER
• HMG CoA is cleaved by HMG CoA lyase
• Acetoacetate and Acetyl CoA is
produced
• Acetoacetate can be reduced to form
Betahydroxybutyrate
• Acetoacetate can also spontaneously
decarboxylate in Blood
• Forms Acetone, a volatile, biologically
nonmetabolized compound
• Acetone can be released in breath
 KETOLYSIS
‘’Use of Ketone Bodies by Peripheral Tissues’’
• Liver constantly synthesizes low levels of ketone
bodies
• When ketone bodies are needed to provide
energy to the peripheral tissues;
• Their production becomes much more significant
during fasting
 KETOLYSIS
‘’Use of Ketone Bodies by Peripheral Tissues’’

• Betahydroxybutyrate is oxidized to Acetoacetate by

Betahydroxybutyrate dehydrogenase, producing NADH
• In Peripheral tissues;
• Acetoacetate is converted to Acetoacetyl CoA
• Reaction is catalyzed by Succinyl CoA:Acetoacetate CoA
transferase (=Thiophorase)
• Succinyl CoA is provided by Krebs cycle
• Acetoacetyl CoA, is actively removed by its conversion to 2
Acetyl CoA
• Liver;
• Produces Ketone bodies
• Lacks Thiophorase
• So; Unable to use Ketone bodies as fuel

• Red Blood Cells lacking mitochondria can not use Ketone

bodies as fuel

• Extrahepatic tissues, including Brain;

• Efficiently oxidize Acetoacetate and Betahydroxybutyrate
• Can use Ketone bodies as fuel
• When the rate of formation of ketone bodies is
greater than the rate of their use;
• Levels begin to rise in Blood (Ketonemia) and,
eventually, in Urine (Ketonuria)
• Seen most often in cases of Uncontrolled Type 1
Diabetes mellitus
 Diabetic Keto Acidosis (DKA)
• Frequent symptom; Fruity odor on breath,
which results from increased production
of Acetone
• Elevation of Ketone body concentration
in blood results in Acidemia
• Carboxyl group of a ketone body has a
pKa of about 4
• Each ketone body loses a proton (H+)
as it circulates in blood, which lowers pH
 Diabetic Keto Acidosis (DKA)
• Urinary loss of Glucose and Ketone bodies results in
Dehydration
• Increased number of H+ circulating in a decreased
volume of plasma can cause Severe acidosis
(Ketoacidosis)
 MOBILIZATION OF STORED FATS
‘’Lipolysis’’
• Fatty acids stored in White Adipose Tissues, in the form of
neutral Triacylglyceride ( TRIGLYCERIDE )
• Triglycride;
• Serves as the body’s major fuel storage reserve
• Provides concentrated stores of metabolic energy because
they are highly reduced and largely anhydrous
 Free Fatty acids
• Move through cell membrane of Adipocyte
• Bind to plasma Albumin
• Transported to tissues
• Enter cells
• Activated to CoA derivatives
• Oxidized for energy in Mitochondria
• Plasma FFAs cannot be used for fuel by RBCs , which
have no mitochondria
• Brain, too, does not use fatty acids for energy, but the
reasons are less clear
 β- Oxidation of Fatty acids
• Major pathway for catabolism
of fatty acids
• Occurs in Mitochondrial matrix
• 2 carbon fragments are
successively removed from
Carboxyl end of Fatty acyl CoA
• Produces Acetyl CoA, NADH,
FADH2
 “Carnitine shuttle”
• Transports long chain fatty acids from Cytosol into
Mitochondrial matrix
 β-oxidation of Fatty Acids
• Consists of a sequence of 4 reactions
involving β-carbon (Carbon 3)
• Results in shortening the fatty acid chain
by 2 Carbons at the carboxylate end
 β-oxidation of Fatty Acids
• Steps include;
• an oxidation that produces FADH2,
• a hydration step,
• a second oxidation that produces NADH,
• Thiolytic cleavage that releases a molecule of
Acetyl CoA
• 4 steps are repeated for saturated fatty acids
of even-numbered carbon chains (n/2) - 1
times (n is the number of carbons),
• Each cycle produces 1 Acetyl CoA plus 1 NADH
and 1 FADH2
 Energy yield from β-oxidation of
Fatty acid oxidation is HIGH

• Oxidation of a molecule of Palmitoyl CoA to CO2 and H2O

produces 8 acetyl CoA, 7 NADH, and 7 FADH2,
• From which 131 ATP can be generated
 CHOLESTEROL

• Hydrophobic compound, with a single hydroxyl group

located at Carbon 3 of the A ring, to which
• A fatty acid can be attached,
• Producess more hydrophobic Cholesteryl ester
 CHOLESTEROL

• Synthesized by virtually all human tissues

• Liver, Intestine, Adrenal cortex,Ovaries, Testes, and
Placenta, make the largest contributions to the body’s
cholesterol pool
• All carbon atoms in cholesterol are provided by Acetyl CoA
• NADPH provides reducing equivalents
• The pathway is driven by hydrolysis of the high energy
thioester bond of Acetyl CoA and terminal phosphate bond
of ATP
Regulation of Cholesterol Synthesis
• HMG CoA reductase is;
• The major control point for Cholesterol synthesis
• Subject to different kinds of metabolic control
 Regulation of Cholesterol Synthesis
Inhibition by Drugs
• Statin drugs are;
• Structural analogs of HMG CoA
• Reversible, Competitive inhibitors of HMG CoA reductase
 Regulation of Cholesterol Synthesis
Inhibition by Drugs
• Statin drugs are;
• Atorvastatin, Fluvastatin, Lovastatin,
Pravastatin, Rosuvastatin, and
Simvastatin
• Used to decrease Plasma
Cholesterol levels in patients with
Hypercholesterolemia
 DEGRADATION OF CHOLESTEROL

• Cholesterol serves as precursor for Steroid hormones,

Vitamin D, Bile acids
• The ring structure of cholesterol cannot be metabolized to
CO2 and H2O
• Sterol nucleus is eliminated from body by conversion to
Bile acids and Bile salts
• A small percentage of Cholesterol is excreted in stool
 BILE
• Consists of a watery mixture of organic and inorganic
compounds
• Quantitatively the most important organic components;
Phosphatidylcholine (= Lecithin ) and Conjugated Bile salts
• Synthesized in liver
 BILE

• Can either pass directly from Liver into Duodenum through

the common bile duct, or
• Can be stored in Gallbladder when not immediately
needed for digestion
 Bile salts
• Provide the only significant mechanism for
Cholesterol excretion, both as;
• A metabolic product of Cholesterol and
• A solubilizer of Cholesterol in Bile
 Bile salt deficiency @ Cholelithiasis

• Movement of cholesterol from Liver into Bile must be

accompanied by;
• Simultaneous secretion of Phospholipid and Bile salts
• If this dual process is disrupted and
• More cholesterol is present than can be solubilized by
Bile salts and Phosphatidylcholine present
• Cholesterol may precipitate in Gallbladder
• Leads to Cholesterol gallstone disease ( Cholelithiasis )
• Caused by a decrease of Bile acids in Bile
 Nonalcoholic “Fatty Liver”

• Occurs in conditions in which there is an imbalance

between hepatic TG synthesis and secretion of VLDL
 Lipoprotein (a)
• Consists of 1 mol of LDL attached to 1 mol of apo (a)
• Apo (a) shows structural homologues to Plasminogen
• Lipoprotein (a) excess increase;
• Risk of premature coronary heart disease due to
Atherosclerosis
• Risk of Thrombosis due to inhibition of fibrinolysis
• Niacin reduces Lp(a), as well as LDL- Cholesterol and
Triglyceride, and raises HDL