Introduction of lipids
Sources of lipids
Classification of lipids
Trans fat
Alteration of dietary fats during food processing
Digestion, absorption of lipids
Absorption of cholesterol
Lipid transport
Lipid metabolism
Biosynthesis of fatty acids
Essential fatty acids
Oxidation of fatty acids
Impact of diet on fatty acids synthesis
Cholesterol synthesis and excretion
2. Function of lipids
Their solubility in organic solvent such as ether, chloroform and acetone makes
lipid with a broader range of functions in metabolic and physiological processes.
These include:
Dietary sources of energy;
Constituents of cell and organelle membranes;
Fat-soluble vitamins;
Corticosteroid hormones;
Mediators of electron transport, such as coenzyme Q.
Energy can be stored for a prolonged period of time only in the form of lipids.
Lipids stored in the body in adipose tissue has the following functions:
Provide insulation;
Help to control body temperature;
Physical protection to internal organs.
2
3. Introduction
Some lipids are essential nutrients because they cannot be synthesized in the
body.
In most Western countries, dietary lipid provides between 30–40% of total
dietary energy. In Asian countries and throughout the developing world, the
proportion of energy derived from dietary lipids is usually much lower.
Triacylglycerols(triglycerides) make up the bulk of dietary lipid with
phospholipids and sterols making up nearly all the remainder.
3
4. Sources of dietary lipids
Animal sources:
Animal adipose tissue
Milk
Products derived from milk fat (cream, butter, cheese and yoghurt)
Eggs
Fish oil
Plant sources:
Vegetable seeds
Nuts
Avocado
Plant leaves
Processed or home prepared foods such as pies, cakes, biscuits and chocolates.
4
5. Classification of lipids
1.Simple lipids
a.Fatty acids
b.Triacylglycerols, diacylglycerols, and monoacylglycerols
c.Waxes (esters of fatty acids with higher alcohols)
I.Sterol esters(cholesterol–fatty acid esters)
II.Nonsterol esters(vitamin A esters, and so on)
II.Compound lipids
a.Phospholipids
i. Phosphatidic acids (i.e., lecithin, cephalins)
ii.Plasmalogens
iii.Sphingomyelins
b.Glycolipids (carbohydrate-containing)
c.Lipoproteins (lipids in association with proteins)
5
6. Classification of lipids
3.Derived lipids (derivatives such as sterols and straight-chain alcohols obtained by
hydrolysis of those lipids in groups 1 and 2 that still possess general properties of
lipids)
4.Ethyl alcohol (though it is not a lipid per se, it does supply dietary energy, and its
metabolism resembles lipid metabolism)
6
7. Triacylglycerols
Triglycerides make up about 95% of dietary lipids .
They are composed of a glycerol, to which three fatty acids are attached by ester
bonds
The fatty acids may be all the same (a simple TAG) or different (a mixed TAG).
The fatty acids in triacylglycerols can be all saturated, all monounsaturated, all
polyunsaturated, or any combination of the three.
The physical and biological properties of triglycerides are determined by the
nature of the constituent fatty acids.
7
32 ESSENTIALS OF HUMAN NUTRITION
H
H
H
C
C
H
OH
HO C (CH2)16CH3
(CH2)7CH=CHCH2CH=CH(CH2)4CH3
(CH2)7CH=CH(CH2)7CH3
free fatty acidsglycerol
O
O
O
C
C
HO
HO
OH
C
O
O
O
O
O
O
C
C (CH2)7CH=CH(CH2)7CH3
triacylglycerol (triglyceride)
C
C
CH
H
H
H
H
(CH2)16CH3
(CH2)7CH=CHCH2CH=CH(CH2)4CH3 3H2O
+
+
+
+
H C OH
Fig. 3.1 Formation of a triglyceride molecule.
8. Triacylglycerols
Acylglycerols may be composed of glycerol
esterified to a single fatty acid (a
monoacylglycerol, MAG) or to two fatty
acids (a diacylglycerol, DAG), with the fatty
acids attached to any of the three carbons of
glycerol.
Although present in the body in small
amounts, the mono- and diacylglycerols are
important intermediates in some metabolic
reactions and may be components of other
lipid classes.
They also may occur in processed foods, to
which they can be added as emulsifying
agents.
A diacylglycerol oil is currently being
marketed as a vegetable oil substitute; the
manufacturer claims that using it in place of a
TAG oil will result in less storage of body fat.
8
9. Triacylglycerols
Triacylglycerols exist as fats (solid) or oils (liquid) at room temperature,
depending on the nature of the component fatty acids.
Triacylglycerols that contain a high proportion of relatively short-chain fatty
acids or unsaturated fatty acids tend to be liquid (oils) at room temperature,
whereas those made up of saturated fatty acids of longer chain length have a
higher melting point and thus exist as solids.
When used for energy, fatty acids are released in free (nonesterified or NEFA)
form as free fatty acids (FFA) from the triacylglycerols in adipose tissue cells by
the activity of lipases, and the FFAs are then transported by albumin to various
tissues for oxidation.
Inserting a double bond in a saturated fatty acid reduces its melting point.
For this reason fats (e.g. butter) containing a predominance of saturated fatty
acids are usually solid at room temperature while oils (e.g. soybean oil) containing
a predominance of polyunsaturated fatty acids are liquid at room temperature.
The position of the unsaturated bonds in mono- and polyunsaturated fatty acids
has a profound influence on their health effects and nutritional properties.
9
10. Phospholipids
Phospholipids comprise a relatively small proportion of total dietary lipid.
The four major phospholipids comprise a diglyceride in which the third position
of the glycerol molecule is occupied by a phosphoric acid residue to which one of
four different base groups is attached (choline, inositol, serine, or ethanolamine).
Along with sphingomyelin these four phospholipids comprise more than 95% of
phospholipids found in the body and in foods.
The structure of the most abundant phospholipid in nature, phosphatidylcholine
(also known as lecithin).
Phospholipids occur in virtually all animal and vegetable foods; liver, eggs,
peanuts, soybeans and wheat-germ are very rich sources.
10
3.1.2 Phospholipids
Phospholipids comprise a relatively small proportion of total dietary lipid. The four
major phospholipids comprise a diglyceride in which the third position of the glyc-
erol molecule is occupied by a phosphoric acid residue to which one of four different
base groups is attached (choline, inositol, serine, or ethanolamine). Along with sphin-
gomyelin these four phospholipids comprise more than 95% of phospholipids found
in the body and in foods. The structure of the most abundant phospholipid in nature,
phosphatidyl-choline (also known as lecithin), is shown in Fig. 3.3. Phospholipids occur
in virtually all animal and vegetable foods; liver, eggs, peanuts, soybeans and wheat-
germ are very rich sources. The base group endows the phospholipid with a polar
region soluble in water while the fatty acids constitute a non-polar region, insoluble in
water. This amphipathic nature—having both polar and non-polar characteristics—of
the phospholipid enables it to act at the interface between aqueous and lipid media so
they make excellent emulsifying agents. The structural integrity of all cell membranes
and lipoproteins is dependent, among other factors, on the amphipathic nature of the
constituent phospholipids. Phospholipids are also an important source of essential fatty
acids.
fatty acid
O
O CH2CH2 N CH3
CH3
H
H C O C
O
fatty acid
H C O C
O
H C O P
O CH3
Choline
O
Fig. 3.3 Structure of
phosphatidylcholine.
11. Phospholipids
The base group endows the phospholipid with a polar region soluble in water
while the fatty acids constitute a non-polar region, insoluble in water.
This amphipathic nature (having both polar and non-polar characteristics) of the
phospholipid enables it to act at the interface between aqueous and lipid media
so they make excellent emulsifying agents.
The structural integrity of all cell membranes and lipoproteins is dependent,
among other factors, on the amphipathic nature of the constituent
phospholipids.
Phospholipids are also an important source of essential fatty acids.
11
12. Sterols
Sterols are monohydroxy alcohols of steroidal structure.
Cholesterol is the principal sterol of animal tissues and is found only in animal
foods, especially eggs, meat, dairy products, fish, and poultry.
It can exist in free form, or the hydroxyl group can be esterified with a fatty acid
called cholesterol ester which is often found in food.
The major sterols of plants (group name phytosterols) are β-sitosterol,
campesterol and stigmasterol.
In the body, this sterol is an essential component of cell membranes, particularly
the membranes of nerve tissue.
Precursor for many other important steroids in the body, including the bile acids;
steroid sex hormones such as estrogens, androgens, and progesterone; the adre-
nocortical hormones; and vitamin D (cholecalciferol, the animal form).
12
Source: New Zealand Food Composition Database (OCNZ88).
3.1.3 Sterols
Sterols are also built up from carbon, hydrogen, and oxygen, but in these lipid com-
pounds, unlike triacylglycerols and phospholipids, the carbon, hydrogen, and oxygen
atoms are arranged in a series of four rings with a range of side chains. Cholesterol
is the principal sterol of animal tissues and is found only in animal foods, especially
eggs, meat, dairy products, fish, and poultry. Cholesterol in food often has a fatty acid
attached to it so it is cholesterol ester (Fig. 3.4). Approximate quantities of cholesterol
in some common foods are given in Table 3.2. The major sterols of plants (group name
phytosterols) are β-sitosterol, campesterol and stigmasterol. Cholesterol plays an impor-
tant structural role in membranes and lipoproteins, and functions as the precursor of
bile acids, steroid hormones, and vitamin D.
13. Other constituents of dietary fats
Dietary fats may also contain small quantities of other lipids including fatty
alcohols, gangliosides, sulphatides, and cerebrosides as well as vitamin E
(tocopherols, tocotrienols), carotenoids (α- and β-carotene, lycopene, and
xanthophylls) and vitamins A and D
13
14. Sphingolipids
Sphingolipids consist of an amino alcohol sphingosine backbone combined with a long-chain
fatty acid through an amide linkage to form ceramide.
Lipids formed from sphingosine are categorized into three subclasses: sphingomyelins,
cerebrosides, and gangliosides. Of these, only the sphingomyelins are sphingophosphatides.
The other two subclasses of sphingolipids contain no phosphate but instead possess a carbohydrate
moiety, called glycolipids.
Sphingomyelins occur in plasma membranes of animal cells. They are particularly abundant in the
myelin sheath of nerve tissues and thus important for nervous system function in higher animals.
The sphingomyelins contain ceramide (a fatty acid residue attached in an amide linkage to the
amino group of the sphingosine), which in turn is esterified to phosphorylcholine.
Sphingomyelins can combine with either phosphorylcholine or phosphorylethanolamine.
14
CH2 CO R1 Figure 5.7 Structure of diphosphatidylglycerol (cardiolipin).
Phosphatidylinositol
Phosphorylation
in plasma
membrane
2 ATPs
2 ADPs
H2O
Phosphatidylinositol-4,5-bisphosphate
Diacylglycerol Inositol-1,4,5-trisphosphate
Activation of
protein kinase C
Release of intracellular Ca21
Enzyme
activation
Enzyme
activation
Other hormonal
responses
Hydrolyzed by
hormone-sensitive
phospholipase C in
plasma membrane to yield
the inositol triphosphate
Ca21 is a second
messenger causing
other hormonal responses.
Figure 5.8 Phosphatidylinositol-4,5-bisphosphate, formed in the
plasma membrane by phosphorylation of phosphatidylinositol.
CH CH
OH
NH
O
O
Ceramide
Amino alcohol spingosine
(R = Fatty acid)
CH3 (CH2)12 CH CH2CH H
RC
With the added fatty acid it is
the sphingolipid, ceramide Figure 5.9 Structure of the sphingolipidceramide.
Structure of the sphingolipidceramide
146 CHAPTER 5 • LIPIDS
For example, they pro
Choline
(CH3)3
OH
NH C R
O
O
O
O
Sphingomyelin
(R = Fatty acid)
+
CH3 (CH2)12 CH CH O NCHCH CH2 CH2 CH2P
Can be phosphorylcholine or
phosphorylethanolamine
Figure 5.
Structure of sphingomyelin
15. Glycolipids
Glycolipids have a carbohydrate component
within their structure and can be subclassified
into cerebrosides and gangliosides.
Their physiological role is principally structural,
and they contribute little as an energy source.
Cerebrosides and gangliosides occur in the
medullary sheaths of nerves and in brain tissue,
particularly the white matter.
Glycolipids have a sphingosine back-bone
attached to a fatty acid by an amide bond, forming
ceramide. The glycolipids do not contain
phosphate.
A cerebroside is characterized by the linking of
ceramide to a monosaccharide unit such as
glucose or galactose, producing either a
glucocerebroside or a galactocerebroside.
15
l
c
f
t
a
a
s
c
g
b
a
e
l
T
M
l
a
p
t
s
c
p
(
f
o
tocerebroside (Figure 5.11).
Gangliosides resemble cerebrosides, except that the
single monosaccharide unit of the cerebroside is replaced
by an oligosaccharide containing various monosaccharide
derivatives, such as N-acetyl neuraminic acid and N-acetyl
galactosamine. Gangliosides are known to be involved in
certain recognition events that occur at the cell surface.
-D-galactose
(R = Fatty acid)
HO
OH H
O
O
CH2OH
CH2H
H
H OH
H
H
NH C
C C
H
HR
OH
C C
O
Sugar can be glucose
(glucocerebroside) or a
galactose (galactocebroside).
Ceramide
Figure 5.11 A galactocerebroside.A galatocerebroside
16. Glycolipids
Gangliosides resemble cerebrosides, except that the single monosaccharide unit
of the cerebroside is replaced by an oligosaccharide containing various
monosaccharide derivatives, such as N-acetyl neuraminic acid and N-acetyl
galactosamine.
Gangliosides are known to be involved in certain recognition events that occur at
the cell surface. For example, they provide the carbohydrate determinants of the
human blood groups A, B, and O.
16
17. Trans Fatty acids
Double-bonded carbon atoms can exist in either a cis or a trans orientation.
Though most natural fats and oils produced by plants or mammals contain only
cis double bonds, some trans fatty acids are derived from the fats of ruminants,
cows, sheep, and goats; others are made by food manufactures.
For example, milk fat contains 4% to 8% trans fatty acids.
Much larger amounts of trans fatty acids are industrially produced by partially
hydrogenating natural fats and oils.
Trans fatty acids are found in certain margarines and margarine-based products,
shortenings, frying fats, and baked goods that use these products.
The reason for the concern about dietary trans fat is its association with increased
levels of risk factors for cardiovascular and other chronic diseases. These include
systemic inflammation, a decrease in HDL levels, and an increase in LDL levels.
Some reports suggest that trans fat also increases adiposity and insulin resistance.
17
18. Dietary fats altered during food processing
The food industry incorporates fats and oils into margarines, biscuits, cakes,
chocolates, pies, sauces and other manufactured food products.
In addition to using naturally occurring lipids, food manufacturers use fats and
oils which have been altered by the process of hydrogenation, adding hydrogen
atoms to the double bonds in mono- or polyunsaturated fatty acids in order to
increase the degree of saturation of the fatty acids in the oil (i.e. reduce the
number of double bonds) and consequently increase the melting point of the fat.
The hydrogenation of the fatty acids or TAG changes the melting point,
giving the product a higher degree of hardness (so that it remains solid at
room temperature) and plasticity (spreadability), which are desirable to both
the consumer and the food manufacturer.
Frying oils have also been hydrogenated to enhance their stability at frying
temperatures. Higher frying temperatures reduce the uptake of the fat during
cooking.
During the dehydrogenation process, electronic shifts cause remaining,
unhydrogenated cis double bonds to revert to a trans configuration that is
energetically more stable.
18
19. Dietary fats altered during food processing
Trans-unsaturated fatty acids behave biologically like saturated rather than like
cis-unsaturated fatty acid
The most abundant trans fatty acids in the diet are elaidic acid and its isomers
19
the two hydrogen atoms attached to the carbons on the same side of the d
and the molecule bends at the double bond. In trans-fatty acids the hydrogen
on opposite sides of the double bond and the molecule stays straight at the d
(Fig. 3.5). Trans-unsaturated fatty acids behave biologically like saturated
like cis-unsaturated fatty acids. The bulk of trans-fatty acids in hydrogen
monounsaturated (elaidic acid, C18: 1n-9 trans, is the trans, equivalent of o
Fig. 3.5 Structure of a cis and
a trans monounsaturated
fatty acid.
21. Digestion
Because TAG are hydrophobic, their digestion poses a special problem in that digestive
enzymes, like all proteins, are hydrophilic and normally function in an aqueous
environment.
The dietary lipid targeted for digestion is emulsified by an efficient process, mediated
mainly by bile salts.
This emulsification greatly increases the surface area of the dietary lipid, consequently
increasing the accessibility of the fat to digestive enzymes.
Digestive enzymes involved in breaking down dietary lipids in the gastrointestinal tract
are esterases that cleave the ester bonds within triacylglycerols (lipase), phospholipids
(phospholipases), and cholesteryl esters (cholesterol esterase).
Triglycerides must be hydrolyzed to fatty acids and monoglycerides before they are
absorbed.
In children and adults, the process starts in the stomach where the churning action
helps to create an emulsion.
Fat entering the intestine is mixed with bile and further emulsified so that lipids are
reduced to small bile acid-coated droplets which disperse in aqueous solutions and
provide a sufficiently large surface area for the digestive enzymes to act.
21
22. Digestion
Bile acids facilitate the process of emulsification because they are amphipathic.
Lipase enzymes secreted by the pancreas split by hydrolysis each triglyceride
molecule, removing the two outer fatty acids, which can be absorbed with the
remaining monoglyceride.
Some monoglyceride (20%) is rearranged so that the lipase enzymes remove the
third fatty acid.
Phospholipids are hydrolyzed by a phospholipase and cholesterol ester by
cholesterol ester hydrolase.
Esterified cholesterol undergoes hydrolysis to free cholesterol and a fatty acid in
a reaction catalyzed by the enzyme cholesterol esterase.
In the newborn, the pancreatic secretion of lipases is low and fat digestion is
augmented by lingual lipase secreted from the glands of the tongue and by a
lipase present in human milk.
The products of lipid digestion, along with other minor dietary lipids, such as fat-
soluble vitamins, coalesce with bile acids into microscopic aggregates known as
mixed micelles
22
23. H
H
H
Fatty acid
C
H
C
Fatty acid
+ H2O
+ Fatty acid
C
H
Fatty acid
H
H
H
Fatty acid
C
H
C
Fatty acid
C
H
OH
H
H
H
Fatty acid
C
H
C
Fatty acid
+ H2O
+ Fatty acid
C
H
Fatty acid
H
H
H
Fatty acid
C
H
C
Fatty acid
C
H
OH
H
H
H
Fatty acid
C
H
C
Fatty acid
+ H2O
+ 2 Fatty acids
C
H
Fatty acid
H
H
H
OH
C
H
C
Fatty acid
C
H
OH
Location Major events
Mouth
Stomach
Small
intestine
Required enzyme
or secretion Details
Triacylglycerol
Triacylglycerols, diacylglycerols,
and fatty acids
Triacylglycerol, diacylglycerol,
and fatty acids
Emulsified triacylglycerols,
diacylglycerols, and
fatty acid micelles
Minor amount
of digestion
Additional
digestion
Phase I:
Emulsification
Monoacylglycerols and
fatty acids
Phase II:
Enzymatic
digestion
Lingual lipase
produced in the
salivary glands
Gastric lipase
produced in the
stomach
Bile; no lipase
Monoacylglycerol
Diacylglycerol
Diacylglycerol
Pancreatic
lipase produced
in pancreas
Lingual lipase cleaves some
fatty acids here.
Gastric lipase cleaves some
fatty acids here.
Pancreatic lipase cleaves
some fatty acids here.
Table 5.3 Overview ofTriacylglycerol Digestion
25. Absorption
Glycerol and fatty acids with a chain length of less than 12 carbon atoms can
enter the portal vein system directly by diffusing across the enterocytes (cells
lining the wall of the small intestine).
Monoglycerides, fatty acids, cholesterol, lysophospholipids, and other dietary
lipids diffuse from the mixed micelles into the enterocytes of the small intestine
where they are re-synthesized into triglycerides, phospholipids and cholesterol
esters in preparation for their incorporation into chylomicrons.
In general, absorption is efficient, with greater than 95% of dietary lipid absorbed
(triglycerides, phospholipids, and fat-soluble vitamins).
Diseases which impair the secretion of bile (e.g. obstruction of the bile duct),
reduce secretion of lipase enzymes from the pancreas (e.g. pancreatitis or cystic
fibrosis), or damage the cell lining of the small intestine (e.g. coeliac disease) can
lead to severe malabsorption of fat.Under such circumstances, medium-chain
triglycerides can be better tolerated and are often used as part of the dietary
treatment.
25
26. Absorption of cholesterol
An additional 1 g (which is 1,000 mg!) is excreted by the liver into the intestine.
Cholesterol, other sterols and β-carotene are only partially absorbed (less than
30%). Only about half of the intestinal cholesterol is absorbed; the remainder is
excreted in the feces.
Most of the cholesterol from the diet is the ester and must be hydrolyzed to free
cholesterol to be absorbed.
Cholesterol is found in the intestinal micelle, which must pass through the
unstirred-water layer, which acts as a diffusion barrier at the lumen-enterocyte
membrane interphase.
Free cholesterol absorption is an energy-independent process and is facilitated by
specific transporter proteins.
After the cholesterol is absorbed into the enterocyte and transported to the ER,
it is esterified by two membrane-localized enzymes, acyl-CoA .
These enzymes are highly specific for cholesterol and will not esterify plant
sterols. Approximately 70% to 80% of cholesterol entering the lymphatic system
is esterified.
26
27. ❷ Only TAG are acted
upon in the stomach.
Lingual and gastric lipase
hydrolyze medium- and
short-chain fatty acids
from the sn-3 position to
yield 1,2-diacylglycerols.
❸ TAG, DAG, C, CE, and
PL enter the lumen
of the small intestine.
❹ These lipids along with
bile salts form micellar
particles and are acted
upon by intestinal and
pancreatic enzymes.
❶ Dietary lipids include
TAG, C, CE, and PL.
These lipids enter
the stomach largely intact.
❻ Glycerol, glucose, C, and long-chain
FA are absorbed into the enterocyte
with the aid of transfer proteins,
a process that does not require energy.
MAG, DAG, and lysophosphatides are
absorbed into the enterocyte by diffusion.
❼ In the enterocyte ER,
glycerol is converted to α-GP.
Additional α-GP is formed from
glucose by glycolysis. α-GP, FA,
MAG, and DAG are reformed
to TAG. Lysophosphatides are
re-esterified with FA to make PL.
C is esterified to CE.
❽ The reformed lipids, along with apo-B48,
form a chylomicron-like particle that leaves the
enterocyte by exocytosis into the lymph.
Other apolipoproteins are transferred to the
chylomicrons from other lipoprotein complexes.
❺ Short-chain free fatty
acids move directly into the
portal vein toward the liver.
Chylomicron
Figure 5.13 Summary of digestion and absorption of dietary lipids.
Abbreviations:TAG = triacylglycerol, C = cholesterol, CE = cholesterol ester, PL = phospholipid, DAG = diacylglycerol, MAG = monoacylglycerol, FA = fatty acid, and α-GP = α-glycerolphosphate.
29. Lipid transport
Since lipids are not soluble in water, it is necessary for them to be associated with
specific proteins, the apolipoproteins, to make water-miscible complexes.
Apolipoproteins, the protein components of lipoprotein particles, tend to
stabilize the lipoprotein complexes as they circulate in the aqueous environment
of the blood, but they also have other important functions.
They confer specificity on the lipoprotein complexes, allowing them to be
recognized by specific receptors on cell surfaces.
Apolipoproteins also stimulate certain enzymatic reactions, which in turn
regulate the lipoproteins’ metabolic functions.
29
42 ESSENTIALS OF HUMAN NUTRITION
apolipoprotein
cholesterol
cholesterol ester
phospholipid
triacylglycerol
apolipoprotein
Fig. 3.8 Structure of a plasma lipoprotein.
Free fatty acids make up only about 2% of
total plasma lipid and are transported in
the blood as complexes with albumin.
The remainder of lipid in the plasma is
carried as lipoprotein complexes (lipid +
protein = lipoprotein).
30. Lipid transport
Re-formed lipid derived from dietary sources leaves the enterocytes of the small
intestine by exocytosis largely in the form of chylomicrons and enter the
bloodstream via lymph vessels.
Chylomicrons belong to a family of lipid-protein complexes (or particles) called
lipoproteins. Lipoproteins play an important role in transporting lipids.
Chylomicrons are large TAG-rich spherical particles containing TAG, cholesteryl
esters, phospholipids (PL), and vitamins A and E in the core and a monolayer of
PL, free cholesterol, and protein on the surface.
Chylomicrons transport lipids of dietary origin (consist predominantly of
triglycerides) mostly to tissues other than the liver, such as muscle and adipose
tissue (80%). The enzyme lipoprotein lipase, located on the walls of capillary
blood vessels, hydrolyzes the triglycerides allowing the free fatty acids to move
into muscle or heart tissue where they can be used for energy, or into adipose
tissue where they can be stored.
30
31. Lipid transport
During its short life in the circulation (15–30 min), more than 90% of the
triglyceride in the chylomicron is removed.
Much of the remaining lipid (20%) is delivered to the liver in the form of
chylomicron remnants. The fat-soluble vitamins (A, D, E, and K) are delivered to
the liver as part of the chylomicron remnant
Chylomicrons are abundant in the blood after eating food, particularly fatty food,
but are scarce in fasting blood.
The fatty acid composition of the lipids in chylomicrons is largely determined by
the composition of the meal just eaten.
31
32. Lipid transport
Very low-density lipoproteins (VLDL) are large triglyceride-rich particles made
in the liver; the primary function of these lipoproteins is to transport triacylglycerol
made by the liver to other, non-hepatic tissues (heart, muscles and adipose tissue).
The lipid is synthesized in the smooth ER, transferred to the Golgi apparatus, and
excreted from the cell along with the apolipoproteins by exocytosis.
Lipoprotein lipase in the heart has a much stronger affinity for triglyceride than that
in the adipose tissue or muscle so when triglyceride concentration is low, triglyceride
is preferentially taken up by heart tissue.
Following removal of much of the triglyceride from VLDL the remaining remnant
particles are intermediate-density lipoproteins (IDL) which are the precursors of low
density lipoprotein.
Within the muscle cell, the free fatty acids from VLDL and those derived from
hydrolysis of the absorbed diacylglycerols are primarily oxidized for energy, with only
limited amounts resynthesized for storage as triacylglycerols.
Endurance-trained muscle, however, does contain TAG deposits.
In adipose tissue, in contrast, the absorbed fatty acids are largely used to synthesize
TAG, in keeping with that tissue’s storage role.
32
33. Lipid transport
Low-density lipoprotein (LDL) is the end product of VLDL metabolism and
its lipid consists largely of cholesterol ester and cholesterol.
Its surface has only one type of apolipoprotein, apo B100. LDL carries about
70% of all cholesterol in the plasma.
LDL is taken up by the liver and other tissues by LDL receptors.
High-density lipoprotein(HDL) is synthesized and secreted both by the liver
and intestine.
A major function of HDL is to transfer apolipoprotein C and E to chylomicrons
so that lipoprotein lipase can break down the triglycerides in thelipoproteins.
HDL also plays a key role in the reverse transport of cholesterol (i.e. the transfer
of cholesterol back from the tissues to the liver).
HDL can be divided into two subfractions of different densities: HDL2 and
HDL3.
33
34. ESSENTIALS OF HUMAN NUTRITION
Table 3.5 Functions of human plasma lipoproteins
Class Function
Chylomicronsa Transports dietary lipids from intestine to peripheral tissues
and liver
Very low-density lipoprotein (VLDL)b Transports lipids from liver to peripheral tissues
Intermediate-density lipoprotein (IDL)c Precursor of LDL
Low-density lipoprotein (LDL)a transports cholesterol to peripheral tissues and liver
Lipoprotein(a) (LP(a))b ?
High-density lipoprotein (HDL2)a Removes cholesterol from tissues and transfers it to the
High-density lipoprotein (HDL3)b,c liver or other lipoproteins
Albuminb Transports free fatty acids from adipose tissue to peripheral
tissues
a
Orgin: intestine.
b
Orgin: liver.
c
Orgin: very low-density lipoprotein.
36. Role of the Liver and Adipose Tissue in Lipid Metabolism
Liver
The liver plays an important role in the body’s use of lipids and lipoproteins.
Functions of the liver:
Hepatic synthesis of bile salts;
site of synthesis of lipoproteins formed from endogenous lipids and
apolipoproteins;
synthesis of new lipids from nonlipid precursors, such as glucose and amino
acids;
Take up and catabolize dietary lipids delivered to it in the form of
chylomicron remnants and LDL, repackaging their lipids into HDL and
VLDL forms.
36
37. ❶
❷
Dietary nutrients enter the liver through the portal vein. Glucose
can be converted to glycogen or enter glycolysis.
Amino acids enter the amino acid pool and some are metabolized
to produce pyruvate and oxaloacetate.
❸ Short-chain FFA, bound to albumin, enter the fatty acid
pool and are incorporated into TAG.
❹ CR attach to apoA, E binding sites, enter the hepatocyte by
endocytosis, and are taken up by a lysosome. FFA, MAG, DAG, and C
are released.The lipids are reformed to TAG and CE and packaged.
❺
❻
❼
TAG, C, and PL are packaged with apolipoproteins and enter the
circulation as VLDLs or HDLs.
VLDLs deliver the meal‘s lipids to the non-hepatic tissue.
HDL is involved in reverse cholesterol transport.
Dietary
nutrients
To
systemic
circulationGlucose
Glycogen
Glycerol
Hepatocyte
Apoprotein
GLU-6-P
Triose-P
Pyruvate
Acetyl-CoA
Oxaloacetate
TCA cycle
Amino
acids
ALB-FFA
NH3
NH3
Hepatic
veins
Portal
vein
VLDL VLDL
HDLHDL
FFA
DG
MG
Phospholipid
Cholesterol
Biliary excretion
Triacylglycerol
pool
Fatty acid
pool
❶
❷
❸
❹
❺
❻
❼
CR
Figure 5.16 Metabolism in the liver following a fatty meal.
Abbreviations: CR = chylomicron remnant, FFA = free fatty acid, MAG = monoacylglycerol, DAG = diacylglycerol, C = cholesterol, CE = cholesterol ester,TAG = triacylglycerol.
38. Role of the Liver and Adipose Tissue in Lipid Metabolism
Adipose tissue
Energy intake in excess of requirements is converted to fat for storage. Stored fat
in adipose tissue provides the human body with a source of energy when energy
supplies are not immediately available from ingested carbohydrate, fat or
glycogen stores.
The adipose tissue is not involved in the uptake of chylomicron remnants or the
synthesis of endogenous lipoproteins rather it is involved in absorbing TAG and
cholesterol from chylomicrons through the action of lipoprotein lipase.
Adipocytes are the major storage site for triacylglycerol, and a single large
globule of fat constitutes over 85% of the volume of the adipose cell.
Most of the lipid in adipose tissue is derived from dietary lipid and the stored
lipid reflects the composition of dietary fat.
The triacylglycerol stores of adipose tissue are not static but are continually
undergoing lipolysis and re-esterification.
38
39. 156 CHAPTER 5 • LIPIDS
❶
❷
Glucose is metabolized to make acetyl-CoA, which can be converted to fatty acids.
Lipoprotein lipase acts on TAG in chylomicrons (CHYLM) and free fatty acids (FFA), DAG, and glycerol
enter the adipocyte. Glycerol cannot be used and is excreted back into the bloodstream.
❸ Lipoprotein lipase acts on VLDL so TAG, FFA, diglycerides (DAG), monoglycerides (MAG), and
cholesterol enter the cell.
❹ The pathways favor energy storage asTAG. Insulin stimulates lipogenesis by promoting entry of
glucose into the cell and by inhibiting the lipase that hydrolyzes the storedTAG to FFA and glycerol.
Adipocyte
Glucose
Glycerol
Glycerol
GLU-6-P
Triose-P
Pyruvate
Acetyl-CoA
TCA cycle
Blood vessel
FFA
DAG
MAG
❶
❹
CHYLM
LPL TAG
LPL TAG
LPL TAG
VLDL
IDL
LDL
❷
❸
CR
Triacylglycerol
pool
Fatty acid
pool
Figure 5.17 Lipid metabolism in the adipose cell
following a meal.
Abbreviations: CHYLM = chylomicron, DAG = diacylglycerol,
MAG = monoacylglycerol,TAG = triacylglycerol, and
FFA = free fatty acid.
40. Biosynthesis of fatty acids
Saturated and monounsaturated fatty acids can be synthesized in the body from
carbohydrate and protein.
This process of lipogenesis occurs especially in a well-fed person whose diet
contains a high proportion of carbohydrate in the presence of an adequate energy
intake. Insulin stimulates the biosynthesis of fatty acids.
Lipogenesis is reduced during energy restriction or when the diet is high in fat.
Unsaturated fatty acids may be further elongated or desaturated by various
enzyme systems
40
41. Essential fatty acids
Essential fatty acids are those that cannot be synthesized in the body and must
be supplied in the diet to avoid deficiency symptoms.
They include members of the ω6 (linoleic acid) and ω3 (α-linolenic acid) families
of fatty acids.
Essential fatty acid deficiency is rare except in those with severe, untreated fat
malabsorption or those suffering from famine.
Symptoms include dry, cracked, scaly, and bleeding skin, excessive thirst due to
high water loss from the skin, and impaired liver function resulting from the
accumulation of lipid in the liver (i.e. fatty liver).
Deficiency symptoms for the n-6 series that have been identified in adults
include poor growth and scaly skin lesions.
Deficiency symptoms for the n-3 series include neurological and visual
abnormalities.
n-3 fatty acids seem to particularly benefit the nervous system, where DHA is
concentrated and appears to function in photo-receptors and synaptic
membranes.
41
42. Essential fatty acids
DHA thus plays roles in vision, neuroprotection, successful aging, and
memory in addition to its anti-inflammatory and inflammation-resolving
properties as compared to n-6 PUFAs.
Human milk contains more of the essential fatty acids (though the level varies)
than most infant formulas do, as well as the elongated derivatives EPA and DHA.
There is evidence that n-3 essential fatty acids are necessary for neural tissue and
retinal photoreceptor membranes
Linoleic acid and α-linolenic acid are not only required for the structural
integrity of all cell membranes, they are also elongated and desaturated into
longer chain, more polyunsaturated fatty acids that are the precursors to a group
of hormone-like eicosanoid compounds, prostaglandins, and leukotrienes.
Linoleic acid (18:2ω6) is converted to arachidonic acid (20:4ω6) while α-linolenic
acid (18 : 3ω3) is converted to eicosapentaenoic (20 : 5ω3) and docosahexaenoic
(22 : 6ω3) acids.
A high ratio of linolenic to α-linolenic acid in the diet tends to reduce the
amount of α-linolenic acid converted to eicosapentaenoic and docosahexaenoic
acids.
42
43. Eicosanoids
Eicosanoids are biologically active, oxygenated metabolites of arachidonic acid,
eicosapentaenoic acid (EPA), or dihomo-γ-linolenic acid (C20 : 3ω6).
They are produced in virtually all cells in the body, act locally, have short life
spans, and act as modulators of numerous physiological processes including
reproduction, blood pressure, homeostasis, and inflammation.
Eicosanoids are further categorized into prostaglandins/thromboxanes and
leukotrienes.
Thromboxane A2 (TxA2), synthesized in platelets from arachidonic acid,
stimulates vasoconstriction and platelet aggregation (i.e. clumping)
Leukotrienes are believed to be important in several diseases involving
inflammatory or hypersensitivity reactions including asthma, eczema, and
rheumatoid arthritis.
43
44. Eicosanoids
AA-, ALA-, EPA-, and DHA-containing phospholipids or TAG are incorporated
into any of the cell’s membranes or the neutral lipid.
The higher the degree of unsaturation among the fatty acids within a membrane,
the greater the fluidity of that membrane.
The membrane’s fluidity is an important determinant for the hormone-receptor
binding sites.
44
45. Oxidation of fatty acids
Those fatty acids not incorporated into tissues or used for synthesis of
eicosanoids are oxidized for energy.
Oxidation of fatty acids occurs in the mitochondria of cells and involves a
multiple step process by which the fatty acid is gradually broken down to
molecules of acetyl CoA, which are available to enter the tricarboxylic acid cycle
and so to generate energy.
45
46. Impact of Diet on Fatty Acid Synthesis
The rate of fatty acid synthesis can be influenced by diet.
Diets high in simple carbohydrates and low in fats induce a set of lipogenic
enzymes in the liver.
This induction is exerted through the process of transcription, leading to
elevated levels of the mRNA for the enzymes.
The transcriptional response is triggered by an increase in glucose metabolism,
and the triggering substance, though not positively identified, is thought to be
glucose-6- phosphate.
Other studies have confirmed that a very low-fat, high-sugar diet causes an
increase in fatty acid synthesis and in palmitic acid–rich, linoleic acid– poor
VLDL triacylglycerols.
Furthermore, the effect may be reduced if starch is substituted for the sugar,
possibly owing to the slower absorption of starch-derived glucose and a lower
postprandial insulin response.
46
47. Cholesterol synthesis and excretion
Nearly all tissues in the body are capable of synthesizing cholesterol from acetyl-
CoA.
Cholesterol is present in tissues and in plasma lipoproteins as free cholesterol or
combined with a fatty acid as cholesterol ester.
About half the cholesterol in the body comes from synthesis and the remainder
from the diet.
It is synthesized in the body from acetyl CoA via a long metabolic pathway.
Cholesterol synthesis is regulated near the beginning of the pathway, in the liver
by the dietary cholesterol delivered by chylomicron remnants.
In the tissues, a cholesterol balance is maintained between factors causing a gain
of cholesterol (synthesis, uptake into cells, hydrolysis of stored cholesterol esters)
and factors causing loss of cholesterol (steroid hormone synthesis, cholesterol
ester formation, bile acid synthesis, and reverse transport via HDL).
47
48. 48
The specific binding sites and receptors for LDL play a crucial role in cholesterol
balance since they constitute the principal means by which LDL-cholesterol
enters the cells.
These receptors are defective in familial hypercholesterolaemia.
Excess cholesterol is excreted from the liver in the bile either unchanged as
cholesterol or converted to bile salts.
A large proportion of the bile salts that are excreted from the liver into the
gastrointestinal tract are absorbed back into the portal circulation and returned
to the liver as part of the enterohepatic circulation, but some pass on to the
colon and are excreted as faecal bile acids.
Cholesterol synthesis and excretion