Transcript Organic Chemistry

Lipid Biochemistry
Aulanni’am
Biochemistry Laboratory
Chemistry Department
Brawijaya University
Aulani "Biokimia" Presentation 6
Lipids: Hydrophobic molecules
 Fats (animal) and Oils (plant) - energy storage, insulation
– Fatty acid - Long hydrocarbon tail with
carboxly -COOH group at the head.
• Saturated - no double bonds; saturated with H
• Unsaturated - one or more H replaced by double
bond - stays liquid
– Carboxyl groups on fatty acid link to -OH group
on a 3-carbon alcohol (glycerol)
Aulani "Biokimia" Presentation 6
A fatty acid
Aulani "Biokimia" Presentation 6
Building a fat molecule
Aulani "Biokimia" Presentation 6
 Source of stored energy in living organisms
 Lipids contain the elements carbon, hydrogen,
and oxygen
 Glycerol and fatty acids are the building blocks
of lipids
 Examples of lipids are fats and oils
fatty acid
glycerol
Aulani "Biokimia" Presentation 6
For simplicity, the fatty acids will be abbreviated as:
HOOC-R
where "R" simply represents the long carbon chain.
glycerol
+
+
3 fatty acids
=
a fat or oil
=
makes a fatty acid and 3 water molecules, 3 H2O
Since a fat or oil contains 3 fatty acid units, they are sometimes
called triglycerides
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Saturated and unsaturated fats
Aulani "Biokimia" Presentation 6
Phospholipids
 One fatty acid replaced by phosphate PO4 Molecule has Hydrophilic head, and long
hydrophobic tail.
 Fatty acids unsaturated- remains fluid
 Main component of cell membranes
Aulani "Biokimia" Presentation 6
Aulani "Biokimia" Presentation 6
Most Common Fatty Acids in Di- and Triglycerides
Fatty acid
Carbon:Double bonds
Double bonds
Myristic
14:0
Palmitic
16:0
Palmitoleic
16:1
Stearic
18:0
Oleic
18:1
Cis-9
Linoleic
18:2
Cis-9,12
Linolenic
18:3
Cis-9,12,15
Arachidonic
20:4
Cis-5,8,11,14
Eicosapentaenoic
20:5
Cis-5,8,11,14,17
Docosahexaenoic
22:6
Cis-4,7,10,13,16,19
CH3(CH2)nCOOH
Aulani "Biokimia" Presentation 6
Cis-9
Linolenic Acid
Omega-3
Aulani "Biokimia" Presentation 6
Cell membrane- Phospholipid bilayer
Aulani "Biokimia" Presentation 6
Predominant Energy Pathways
Aulani "Biokimia" Presentation 6
We use fat in the form of triglyceride
(3 fatty acids and 1 glycerol).
Aulani "Biokimia" Presentation 6
Fat Metabolism
Mostly handled by the liver
Fats must first be broken down to form
acetic acid which is subsequently oxidized.
Oxidation (breakdown) of fats is not always
complete.
Intermediate
products
accumulate in the blood causing the blood to
become acidic (acidosis or ketosis)
Aulani "Biokimia" Presentation 6
Cholesterol
Structural basis of steroid hormones and
vitamin D
Major building block plasma membranes
15% of cholesterol comes from diet the
rest is made by the liver.
Cholesterol is lost by breakdown, secretion
in bile salt and finally defecation
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Lipoproteins
Fatty acids, fats, and cholesterol are insoluble in
water and therefore are transported bound to
small lipid-protein complexes called lipoproteins
Low-density
lipoproteins (LDL) – transport
cholesterol and other lipids to body cells
High-density
lipoproteins (HDL) – transport
cholesterol from tissue cells to liver for disposal
Ratio of HDL/LDL is important
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Body Energy Balance
When
energy intake and energy outflow are
balanced – body weight remains stable
When they are not, weight is either lost or gained
Control of food intake: ?
– Rising and falling blood levels of nutrients
– Hormones
– Body temperature
– Psychological factors
Aulani "Biokimia" Presentation 6
Basal Metabolic Rate
The amount of heat produced by the body per
unit of time under basal conditions
An average 155lb adult has a BMR of about 6072 kcal/hour
Aulani "Biokimia" Presentation 6
Lipids
Catabolism
 Aerobic
 transport of fatty acids from cytosol to

mitochondria (role of carnitine)
-oxidation in mitochondria
 4 steps
 release of NADH and FADH2
 108 ATP/palmitic acid or 7 ATP/Carbon
Aulani "Biokimia" Presentation 6
 Catabolism: dietary lipids
 Digestion:

a) Slow relative to carbohydrates
b) In small intestine with action of bile salts
c) FAcs absorbed across intestinal wall and
reconverted to TAGs
d) Transported as chylomicrons
Mobilisation from adipocytes:
a) FAcs transported in blood bound to serum
albumin; dissociates in cells  oxidation
b) glycerol undergoes glycolysis
 Role of glucose 6-phosphatase in maintaining blood
glucose levels (in the liver, not the muscles)
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Synthesis: lipogenesis

carried out by two cytosolic enzymes, acetyl-CoA
carboxylase and fatty acid synthase
 Requires: NADPH, ATP and biotin, CO2
 Sources of
 Acetyl CoA - transfer of citrate from mitoch. to
cytosol
 NADPH - malic enzyme in cytosol
- pentose phosphate pathway
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Lipid Digestion - Rumen
-galactosidase
DigalDigly
MonogalDigly
Galactose
Propionate
Glycerol
Triglyeride
CaFA
Lipase
Saturated FA
Ca++
-galactosidase
Diglyceride
Lipase Anaerovibrio
lipolytica
Fatty acids
H+
Reductases
Feed particles
Aulani "Biokimia" Presentation 6
Fat Digestion
Digestibility influenced by:
Dry matter intake
Decreases with greater intake
Amount of fat consumed
Digestibility decreases 2.2% for each 100 g of
FA intake (Response is variable)
Degree of saturation
Digestibility decreases with increased
saturation
Maximal digestion with fats having Iodine
values greater than 40
Aulani "Biokimia" Presentation 6
Lipid Metabolism - In the Rumen
1. Minimal degradation of long-chain fatty acids in
the rumen
Fatty acids not a source of energy to microbes
2. Active hydrogenation of unsaturated fatty acids
3. Microbial synthesis of long-chain fatty acids in
the rumen (15g/kg nonfat org matter fermented)
4. No absorption of long chain fatty acids from the rumen
More fat leaves the rumen than consumed by the animal
Lipids leaving the rumen
• 80 to 90% free fatty acids attached to feed particles
and microbes
• ~10% microbial phospholipids leave the rumen
• Small quantity of undigested fats in feed residue
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Microbial Fatty Acid Synthesis
• Synthesize C 18:0 and C 16:0 in 2:1 ratio using
acetate and glucose (straight-chain even carbon #).
• If propionate or valerate used, straight-chain odd
carbon fatty acids synthesized.
• Branched-chain VFA used to produce branched
chain fatty acids.
• About 15 to 20% of microbial fatty acids are monounsaturated. No polyunsaturated fatty acids are
synthesized.
• Some incorporation of C 18:2 into microbial lipids.
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Hydrogenation of Fatty Acids in the Rumen
Polyunsaturated fatty acids (all cis)
Isomerase (from bacteria)
Needs free carboxyl group
and diene double bond
Shift of one double bond (cis & trans)
Hydrogenation
Hydrases (from bacteria,
Hydrogenated fatty acid
mostly cellulolytic)
(stearic and palmitate)
Aulani "Biokimia" Presentation 6
Hydrogenation of Fatty Acids
in the Rumen
All unsaturated fatty acids can be hydrogenated
Monounsaturated less than polyunsaturated
65 to 96% hydrogenation
Numerous isomers are produced
Biohydrogenation is greater when high forage
diets fed
Linoleic acid depresses hydrogenation of FA
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Conjugated Linoleic Acid - Rumen
Most Common Pathway (High Roughage)
Linoleic acid (cis-9, cis-12-18:2)
Cis-9, trans-12 isomerase
Butyrivibrio fibrosolvens
Conjugated linoleic acid (CLA, cis-9, trans-1118:2)
Vaccenic acid (Trans-11-18:1)
Stearic acid (18:0)
Aulani "Biokimia" Presentation 6
CLA Isomers - Rumen (High Concentrate) Low Rumen pH
Linoleic acid (cis-9, cis-12-18:2)
Cis-9, trans-10 isomerase
CLA Isomer (trans-10, Cis-12-18:2)
This isomer is inhibitory to milk
fat synthesis.
Trans-10-18:1
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Linolenic Acid – Oleic Acid
Linolenic acid (cis-9, cis-12, cis-15-18:3)
(Cis-9, trans-11, cis-15-18:3)
Trans-11, cis-15-18:2
Trans-11-18:1 (vaccenic acid)
Oleic acid cis-9 (18:1)
Stearic acid (18:0)
Aulani "Biokimia" Presentation 6
CLA absorbed from the intestines available for incorporation
into tissue triglycerides.
Reactions from linoleic acid to vaccinic acid occur at a faster
rate than from vaccinic acid to stearic acid.
Therefore, vaccinic acid accumulates in the rumen and passes
into intestines where it is absorbed.
Quantities of vaccinic acid leaving the rumen several fold
greater than CLA.
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Conversion of Vaccinic Acid to CLA
In mammary gland and adipose
Trans-11-18:1
CLA, cis-9, trans-11 18:2
Stearoyl CoA Desaturase
‘9-desaturase’
This reaction probably major source of CLA in
milk and tissues from ruminants.
Also transforms
Palmitic
Stearic
Palmitoleic
Oleic
Aulani "Biokimia" Presentation 6
Synthesis: lipogenesis

carried out by two cytosolic enzymes, acetyl-CoA
carboxylase and fatty acid synthase
 Requires: NADPH, ATP and biotin, CO2
 Sources of
 Acetyl CoA - transfer of citrate from mitoch. to
cytosol
 NADPH - malic enzyme in cytosol
- pentose phosphate pathway
Aulani "Biokimia" Presentation 6
 Synthesis: lipogenesis
 Other roles of PPP
 alternative pathway for glucose metabolism
 production of ribose 5-phosphate (nucleotide
synthesis)
 Ketone bodies arise from the overflow pathway in
liver; major source of energy for heart, muscle and
brain (fasting and diabetes)
 Location of lipid metabolism
 oxidation in mitoch., synthesis in cytosol
Aulani "Biokimia" Presentation 6
Summary of fatty acid metabolism in the liver
Aulani "Biokimia" Presentation 6
 If excess fat is consumed, there is no mechanism
by which the body can increase its use of fat as a
fuel.
 Instead, when excess fat calories are consumed,
the only option is to accumulate the excess fat as
an energy store in the body, and this process
occurs at a low metabolic cost and is an extremely
efficient process.
Aulani "Biokimia" Presentation 6
Aulani "Biokimia" Presentation 6