Fats and Lipids

1
Fats and Lipids
2
Lipids

• Functions
• Energy
• thermal insulation
• electrical insulators
• structural components
• transportation of lipids
• hormones and vitamins

3
Classification of the Lipids

• Simple lipids
• Esters of Fatty Acids with various alcohols
• Compounds lipids
• Esters of Fatty Acids with alcohol and containing
  other groups
• Phospholipids
• Glycolipids
• Others

4
Classification of Lipids

• Derived Lipids
• breakdown products of lipids
• Fatty acids, glycerol

5
An example of a derived lipid is..

• Triglyceride
• Sucrose polyester
• Fatty acid
• glycogen
• None of the above

6
Fatty Acids

• Nomenclature
• Saturated -anoic
• Unsaturated -enoic
• Chain length
• number of carbons indicated by C20 for 20 Carbon
  long fatty acid
• Number of double bonds
• 2 double bonds C202

7
Fatty Acids Nomenclature

• Omega Methyl group orientation
• omega 3, omega 6, omega 9
• humans cant form double bonds before omega 9
• Carboxylic acid orientation
• delta 9
• Carboxylic acid end
• Alpha end
• This end bonds with the glycerol

8
An omega 9 fatty acid is.

• An essential fatty acid
• One which the body can make
• One which the body needs in the diet
• 1 and 3
• 1 and 2

9
Fatty Acid Elongation

• Omega 9 Series
• Oleic Acid C181
• Can add a 2C segment and double bond after omega-9

10
Essential Fatty Acids

• Those Fatty Acids that cant be synthesized but
  are required.
• In humans
• linoleic 182 omega 6
• Or other omega 6 fatty acids
• alpha linolenic 183 omega 3
• Or other omega 3 fatty acids

11
Essential Fatty Acid Functions

• Fat Transport
• Components of Membranes
• Blood Clotting
• Prostaglandins/Eicosanoids

12
Requirements for Essential Fatty Acids

• Approximately 2 of total Calories
• 2000 Cal diet X .02 40 Calories
• 40 Cal/9 Cal/gram 4.44 grams
• corn oil 59 linoleic acid _at_ 8 g/Tbsp.
• approx.. 1/2 Tbsp./day

13
Prostaglandins

• Prostaglandins were first discovered and isolated
  from human semen in the 1930s by Ulf von Euler of
  Sweden.
• Thinking they had come from the prostate gland,
  he named them prostaglandins.
• However, they exist and are synthesized in
  virtually every cell of the body

14
Prostaglandins

• Prostaglandins, are like hormones in that they
  act as chemical messengers, but do not move to
  other sites
• They work right within the cells where they are
  synthesized.

15
Prostaglandins..

• Were named by a guy from Sweden(Ulf von Euler)
• He thought they came from the prostate gland
• They act on the cells they are produced in
• 1 and 2
• 1, 2 and 3

16
Prostaglandins

• Series 2 Prostaglandins are unsaturated
  carboxylic acids, consisting of a 20 carbon
  skeleton that also contains a five member ring.
• They are biochemically synthesized from the fatty
  acid, arachidonic acid.

17
Prostaglandin Formation

• The unique shape of the arachidonic acid caused
  by a series of cis double bonds helps to put it
  into position to make the five member ring.
• Cis double bonds cause the molecule to bend
• Arachidonic Acid omega 6 C204
• Can you draw it?
• It might be on the next test!!

18
Omega 6 C204 correctly describes

• Linoleic acid
• glycerol
• Arachidonic acid
• A complex lipid
• None of the above

19
(No Transcript)
20
(No Transcript)
21
Prostaglandin/Eicosanoid Function

• Many and varied
• extremely potent nanogram quantities (1X10-9
  grams)
• Effect of eicosanoid depends on the source
  molecule
• Series 1 from dietary linoleic 182 omega 6
• Series 2 from arachidonic acid or series 1
• Series 3 from dietary omega 3 fatty acids

22
Series 3 Prostaglandins are derived from

• Arachidonic acid
• Omega 6 fatty acids
• Omega 3 fatty acids
• Omega 9 fatty acids
• All of the above

23
Functions of Prostaglandins Series 2

• Activation of the inflammatory response,
  production of pain, and fever.
• When tissues are damaged, white blood cells flood
  to the site to try to minimize tissue
  destruction.
• Prostaglandins are produced as a result.

24
Varied Effects Series 2

• Blood clots form when a blood vessel is damaged.
• A type of prostaglandin called thromboxane
  stimulates constriction and clotting of
  platelets.
• Conversely, PGI2, also called prostacyclin, is
  produced to have the opposite effect on the walls
  of blood vessels by causing vasodilation.
• This occurs where clots should not be forming.

25
Varied Functions Series 2

• Certain prostaglandins are involved with the
  induction of labor and other reproductive
  processes.
• PGE2 causes uterine contractions and has been
  used to induce labor.

26
Varied Functions

• Series 2 Prostaglandins are involved in several
  other organs such as
• The gastrointestinal tract (inhibit acid
  synthesis and increase secretion of protective
  mucus),
• The renal tissue to increase blood flow in
  kidneys, and
• The lungs where leukotrienes promote constriction
  of bronchi associated with asthma.

27
Compare Series 2 with Series 3

• Series 2 are derived from Omega 6 Fatty acids
• Series 3 are derived from Omega 3 Fatty acids or
  a diet rich in fish oil tend to be
• Anti-clotting
• Cause vasodilation

28
Functions of Series 2 Eicosanoids from a diet
rich in omega 6 fatty acids

• Series 2 Thromboxane
• causes aggregation of platelets clotting
• inhibits vasodilation
• therefore a diet high in omega 6 fatty acids
  results in a high ability to clot and keep the
  blood vessels constricted.
• Could contribute to myocardial infarction

29
Series 3 Properties

• Omega 3 fatty acids
• Thromboxane 3
• Inhibits aggregation (clotting)
• Reduces the likelihood of clotting
• Therefore a diet high in omega 3s have a lower
  tendency to clot
• Reduce the risk of Myocardial Infarction

30
Series 3 Thromboxane

• Is derived from arachidonic acid
• Reduces clotting
• Increases blood pressure
• Contributes to MI
• All of the above

31
Other Effects of Omega 3s

• Inhibition of hepatic Triglyceride synthesis
• Increase cell membrane fluidity
• 15 reduction in blood viscosity
• RBCs can fit through smaller spaces
• Decreased blood pressure
• series 3 prostacyclin is a vasodilator

32
How Were Omega 3s Discovered?

• Dyerberg and Bang, 1978 noticed decreased CVD,
  decreased cholesterol and triglycerides, and
  increased bleeding times in Greenland Eskimos
• Consumed fish, and other marine animals
• high in Eicosapentaenoic acid(omega 3 C205)
• starting point for Series 3 Eicosanoids

33
The eskimo diet would be high in ______ resulting
in _______.

• Omega 6 heart disease
• Omega 3heart disease
• Omega 6 reduced risk of heart disease
• Carbohydrates cancer
• Omega 3 reduced risk of heart disease

34
How Much Fish Do We Need to Eat to Get the
Positive Effects?

• Kobayashi, Lancet 1981 Japanese Fishermen eating
  1/2 pound per day decreased platelet aggregation
  and blood viscosity when compared to Japanese
  farmers
• Kromhout, NEJM 1985 Netherlands 20 yr CVD
  reduced by 50 when at least 30 grams (1 ounce)
  of fish eaten daily

35
Drugs and Eicosanoids

• Aspirin salicylic acid Cyclooxygenase inhibitor
• found in willow bark, chew on willow when you
  have a headache
• inhibits cyclooxygenase in arachidonic acid
  metabolism
• Negative effect increased risk of stomach
  irritation and ulceration and bleeding
• Indomethacin (Indocin)
• Also a Cyclooxygenase inhibitor

36
How does Aspirin Work?

• Aspirin blocks an enzyme called cyclooxygenase,
• Two isoenzymes COX-1 and COX-2, are involved
  with the ring closure and addition of oxygen to
  arachidonic acid converting to prostaglandins.
• COX-1 inhibition anti-inflammatory
• COX-2 inhibition increased gastric acid
  secretion, stomach irritation and bleeding and
  platelet aggregation

37
How does aspirin work?

• The acetyl group on aspirin is bonded to serine,
  part of the enzyme which blocks the channel in
  the enzyme and arachidonic acid can not enter the
  active site of the enzyme.
• The acetyl group changes the conformation of the
  enzyme. SHAPE CHANGES

38
(No Transcript)
39
Aspirin works by

• Blocking the formation of arachidonic acid
• Blocking the formation of prostaglandin 2
• Filling the active site in Cyclooxygenase
• 1 and 2
• 2 and 3

40
Drugs and Eicosanoids

• Ibuprofen advil, motrin, nuprin
• not totally understood
• may be through eicosanoid inhibition
• COX-2 inhibition results in anti-inflammatory
  response and COX-1 inhibition results in GI tract
  and stomach irritation and ulceration
• Ibuprofen(advil, motrin) no ulceration COX-2?
• aspirin stomach ulceration COX-1 COX-2?
• Therefore probably different mechanism than
  aspirin

41
Aspirin and ibuprofin (advil) probably work
through exactly the same mechanism to relieve
pain.

• True
• False

42
Aspirin and Prostaglandins

• By inhibiting or blocking the cyclooxygenase
  enzyme, the synthesis of prostaglandins is
  blocked, which in turn relieves some of the
  effects of pain and fever.
• Aspirin is also thought to inhibit the
  prostaglandin synthesis involved with unwanted
  blood clotting in coronary heart disease.
• A potential negative aspirin may cause more
  extensive bleeding in other locations in the
  body, including stomach

43
Drugs and Eicosanoids

• Acetamenophen Tylenol, cotylenol, dristan,
  Anacin-3
• works through hypothalamus to decrease temperature

44
Isomerization in Unsaturated Fatty Acids

• Geometric Isomers Depends on orientation of
  groups around carbons
• Cis same side
• Trans opposite side

45
Hydrogenation of Unsaturated Fatty Acids

• To reduce the risk of oxidative rancidity
• To make more solid at room temperature
• Hydrogenation results in making the Fatty acid
  more saturated
• It also results in mistakes cis double bonds
  flip and become trans double bonds

46
Why do food producers hydrogenate unsaturated
fatty acids?

• Reduce the risk of oxidative rancidity
• Make solid at room temperature
• To make more unsaturated
• 1 and 2
• 2 and 3

47
Trans Fat Information on Nutrition Facts Panels

• Under FDA guidelines, as of January 1, 2006,
  trans fat must be listed on food labels in the
  U.S.

48
Increase risk of Chronic Disease

• Harvard School of Public Health researchers have
  found that removing trans fats from the
  industrial food supply could prevent tens of
  thousands of heart attacks and cardiac deaths
  each year in the U.S. April 13, 2006 issue of the
  New England Journal of Medicine.
• Trans Fat increases LDL cholesterol increases
  LDL/HDL cholesterol ratio

49
Lipid Profile in the Blood

• Total Cholesterol lt 200 mg/dl
• LDL Cholesterol lt 130 mg/dl
• HDL Cholesterol gt45 mg/dl
• Ratios TChol/ HDL 4 or less is good
• LDL-c/HDL-c 2.8 or less is good
• Increasing the ratios increases risk of CHD

50
(No Transcript)
51
Which of the following LDL to HDL-c ratios would
be considered good, or preventative related to
CHD?

• 20
• Greater than 200
• Less than 2.8
• Greater than 4
• Between 8 and 16

52
Trans Fat and Sat Fat

• Both increase ratios of LDL/HDL cholesterol
• Increase risk of CHD
• At same percent of total kcals, Trans fat
  increases ratio greater than Sat Fat

53
Trans Fat

• Trans fatty acids do not relieve symptoms of
  essential fatty acid deficiency
• You are what you eat trans fatty acids are
  incorporated into cell membranes and other tissue

54
Oxidative Rancidity

• Polyunsaturated Fatty Acids are subject to
  Oxidative Rancidity
• Especially with no anti-oxidants(vit E, C,
  selenium, vit A, and with the presence of oxygen,
  warmth and heavy metals)
• Free radicals are formed
• Very reactive cause damage to cells and DNA

55
Free Radicals React with Other PUFAs

• Form hydroperoxides and a new free radical
• hydroperoxides give the off-odor and off-flavors
  of rancid food
• Free radicals increased with high PUFA diet, low
  levels of anti-oxidants(vit E, C, A, selenium),
  presence of heavy metals(Cu, Cd, Pb, and Hg)

56
Protection Against Free Radical Formation

• Vit E, C, Se, BHA and BHT in food
• Good care taken with PUFAs
• Store in airtight containers
• Away from heavy metals
• Refrigerated if not used for a while
• Use up quickly

57
Oxidative rancidity may occur more rapidly under
all but one of the following conditions.

• Warm environment
• Oxygen filled space
• Contact with heavy metals
• If kept in air tight containers

58
Vitamin E as an Antioxidant

• New York Academy of Science, 1988
• N40 20 smokers and 20 non-smokers
• A 10 smokers Vit E
• B 10 smokers placebo
• C 10 non-smokers Vit E
• D 10 non-smokers placebo
• B 3x more RBC damage than A, C, or D

59
Types of Lipids

• Acylglycerols Triglycerides
• Phospholipids Lecithin
• Sterols Cholesterol

60
Acylglycerols

• Most common triglyceride
• Glycerol 3 fatty acids
• Classed as fats (if solid) or oils (if liquid) at
  room temperature
• Dependant on degree of saturation and chain
  length
• saturated more solid versus unsaturated

61
The most common acylglycerol in diet is

• Cholesterol
• Triglyceride
• Fatty acid
• Phospholipid
• Trans Fatty Acid

62
Medium Chain Triglycerides

• MCT rare in nature but derived from coconut oil
  for therapeutic use.
• FAs are 6 to 10 Carbons long
• liquid at room temperature
• dont require bile because they are somewhat
  soluble in water
• Used with pts with impaired fat absorption to
  increase Kcal

63
MCT are used to provide energy to those who have
impaired glucose absorption.

• True
• False

64
Phospholipids

• 2nd most abundant group of lipids
• glycerol, 2 fatty acids, 1 phosphate containing
  group
• Phosphatidic acid is the backbone
• Phosphatidyl choline (lecithin) common
  phospholipid

65
Sterols

• Found associated with fat in food body
• Cholesterol parent compound for all steroids and
  sterols synthesized in body
• Occurs only in animal tissue, not plants
• Widely synthesized from acetate (2C)
• precursor of cholic acid, part of bile
• precursor of Vit D and sex hormones

66
(No Transcript)
67
Cholesterol Functions

• Structure component in membranes
• precursor to Vit D, bile, hormones
• precursor to gluco- and mineral-corticoids
• Adrenal Cortex
• cortisone glucocorticoid anti-inflammatory
• aldosterone mineralcorticoid water balance,
  mineral balance

68
(No Transcript)
69
Adrenocorticoid Hormones

• The adrenocorticoid hormones are products of the
  adrenal glands ("adrenal" means adjacent to the
  renal (kidney).
• Aldosterone, a mineralcorticoid, regulates the
  reabsorption of sodium and chloride ions in the
  kidney tubules and increases the loss of
  potassium ions. Secreted when blood sodium ion
  levels are too low. Causes the kidney to retain
  sodium ions. Aldosterone also controls swelling
  in the tissues.

70
Cortisol

• Cortisol, the most important glucocorticoid, has
  the function of increasing glucose and glycogen
  concentrations in the body.
• These reactions are completed in the liver by
  taking fatty acids from lipid storage cells and
  amino acids from body proteins to make glucose
  and glycogen.

71
Cortisone

• Cortisol and its ketone derivative, cortisone,
  have the ability to control inflammatory effects.
  
• Cortisone or similar synthetic derivatives such
  as prednisolone are used to treat inflammatory
  diseases, rheumatoid arthritis, and bronchial
  asthma.

72
Adrenocorticoid hormones.

• Come from the renal gland
• Are sterols
• Are phospholipids
• 1 and 3
• 1 and 2

73
Metabolism of Cholesterol

• Sources
• Exogenous dietary 200mg to 2000 mg/day
• Endogenous synthesis in body highly variable
• Serum cholesterol The cholesterol in blood
• High serum cholesterol risk factor for heart
  disease

74
Control of Serum Cholesterol

• First level decreased synthesis
• HMG CoA Reductase is rate limiting enzyme
• Second level decreased absorption
• Third level bile loss in feces
• requires liver to make more bile from existing
  cholesterol
• this tends to lower level of serum cholesterol

75
Bile Composition

• Bile is made of
• Cholesterol
• Phospholipids
• Bile pigments bilirubin and bilivirdin
• Bile salts glycocholate and taurocholate
• Bicarbonate ion

76
Serum lipid response to dietary cholesterol

• Am J Clin Nutr 198950 58-62.
• Low-fat, high fiber diet
• n58 fed 9, 0, 9 eggs per week over 3
  consecutive months
• No change seen in total chol, LDL-chol, HDL-chol
• Conclusions with lowfat, high fiber, lt 400mg
  chol/day offer no added benefits

77
Decreased absorption Methods to enhance reduced
absorption

• Plant sterol-enriched margarines Take Control,
  Benecol, and Benecol Light have been shown to
  reduce serum LDL cholesterol
• Phytosterols, found in fat soluble fractions of
  plants, chemically resemble Cholesterol
• Inhibit cholesterol absorption
• Cost about 3 times as much for consumers

78
Plant sterols are recognized for their ability to

• Reduce absorption of cholesterol in the gut
• Increase trigyceride formation
• Enhance absorption of fat soluble molecules
• Promote recycling of bile

79
Example of a study Nigon, et alPlant
sterol-enriched margarine lowers plasma LDL in
hyperlipidemic subjects with low cholesterol
intakeClin Chem Lab Med 2001 jul 39(7) 634-40.

• Randomized double blind placebo-controlled
  two-period cross-over trial with two treatments
  and three periods.
• Both treatment periods lasted 2 months with a 2
  month washout period between
• Sterol enriched spread compared to non-enriched
  spread
• N 53 hypercholesterolemic patients(31 females
  and 22 males)

80
Phytosterols

• 58 12 years BMI 23.5 2.8 kg/m2
• No adverse side-effects noted
• Plasma total and LDL-C reduced 6.4 and 8.8
  respectively
• No effects on HDL-C
• Conclusions Spreads with phytosterols may
  enhance serum cholesterol control

81
Fat Replacers

• Carbohydrate based
• fruit based(Prune Paste)
• grain-based(Betatrim)
• polydextrose(Litesse)
• Protein based
• egg and milk protein(Simplesse)
• Fat based
• sucrose polyester(Olean)

82
Fat Digestion

• Triglycerides
• pancreatic lipase in lumen
• glycerol
• 40-50 free fatty acids
• 40-50 monoglycerides
• lt 10 di- and tri-glycerides
• These enter the mucosa

83
Which of the following are the results of
triglyceride digestion?

• Glycerol
• Fatty acids
• Some monoglycerides
• 1 and 2
• 1, 2, 3

84
Fat Digestion and Absorption

• Mucosa receives the end products of triglyceride
  digestion
• sends some glycerol and fatty acids directly to
  the portal vein for transport to the liver
• manufactures triglyceride from rest of the
  digestion products
• incorporates into chylomicrons for transport in
  the lymphatics to the liver

85
Cholesterol Digestion and Absorption

• Free cholesterol absorbed into mucosa then
  transported in the lymphatics with chylomicrons
• Some free cholesterol combine with fatty acids to
  form cholesterol esters in lumen
• These are absorbed and transported in lymphatics
  in chylomicrons

86
Lipid Transport

• Short and medium chain fatty acids and glycerol
  can be transported in the blood
• Long chain fatty acids and cholesterol and
  cholesterol esters transported by Lipoproteins
  called chylomicrons
• Enter the lymph system and eventually end up in
  the liver

87
Other Lipoproteins

• Liver Production of Very Low Density Lipoprotein
  (VLDL)
• transports triglycerides (TG) and cholesterol
• Low Density Lipoprotein (LDL) as VLDL drops off
  TG, VLDL becomes LDL with high cholesterol
  content.
• High LDL-cholesterol in blood increases risk for
  plaque build up in arteries

88
High Density Lipoprotein

• HDL produced in liver
• Main task is to pick up cholesterol in tissues
  and transport back to liver for re-use or
  conversion to cholic acid for bile production
• High HDL-cholesterol is protective against heart
  disease
• picks up cholesterol from peripheral tissue and
  takes back to liver.